Ischemia-reperfusion Injury In Rats Research Articles

Cardioprotective effect of Perakine against myocardial ischemia-reperfusion injury of type-2 diabetic rat in Langendorff-Perfused Rat Hearts: Role of TLR4/NF-kB signalling pathway.

Myocardial ischemia-reperfusion (I/R) injury is a grave life-threatening situation, if not treated well in time. The development of natural remedies for myocardial I/R injury has witnessed dramatic growth in the last decade. Prompted by the above, in the present study, we have elucidated the pharmacological effect of Perakine (PER), an indole alkaloid in myocardial ischemia-reperfusion injury in type 2 diabetic rats. The model was established by inducing diabetes in experimental rats followed by the development of myocardial I/R injury model of isolated rat heart by the use of improved Langendorff retrograde perfusion technology. Results of the study suggest that PER significantly lowered the infarct size and infarct volume, and improvement in cardiac ability (LVSP, ±dP/dtmax, and heart rate). It also showed a significant lowering of cardiac biomarkers (CK, CK(MB), ALT, AST, and LDH) in a dose-dependent manner as compared to unprotected IR rats. The level of oxidative stress (MDA, SOD, and GSH) was also found lowered in IR rats together with a reduction in the production of pro-inflammatory cytokines (IL-1β, IL-6, IL-17, and TNF-α). The anti-inflammatory acting of PER on IR rats is believed to be linked with the reduction of TNF-α, NF-κB, and TLR4 in both RT-qPCR and western blot analysis. Our research showed that Perakine could potentially alleviate cardiac ischemia-reperfusion injury in rats by blocking the TLR4/NF-κB signaling cascade.

Exercise preconditioning mitigates brain injury after cerebral ischemia-reperfusion injury in rats by restraining TIMP1.

Cerebral ischemic disease is a common cerebrovascular disease, especially ischemic stroke. Exercise has protective functions on brain tissues following cerebral ischemia-reperfusion injury (CIRI), but its preventive effects and mechanisms in CIRI remain unclear. We aimed to investigate the effects and mechanisms of exercise preconditioning on CIRI. The middle cerebral artery occlusion (MCAO) operation was prepared to establish CIRI rats. All rats were randomized into the MCAO, exercise (exercise preconditioning plus MCAO operation), vector (exercise preconditioning, MCAO operation plus intraventricular injection of empty vector), and tissue inhibitor of metalloprotease 1 overexpression (OE-TIMP1, exercise preconditioning, MCAO operation plus intraventricular injection of OE-TIMP1) groups. The results indicated that exercise preconditioning suppressed approximately 66.67% of neurological deficit scores and 73.79% of TIMP1 mRNA expression in MCAO rats, which were partially offset by OE-TIMP1. The protective effects of exercise against neuron death status and cerebral infarction size in MCAO rats were reversed by OE-TIMP1. It also confirmed that exercise weakened apoptosis and oxidative stress damage, with notable increases of B-cell lymphoma-2, superoxide dismutase, and glutathione peroxidase production, and evident decreases of BCL2-associated X, caspase 3, and malondialdehyde in MCAO rats, while these effects were partially reversed by OE-TIMP1. Additionally, the inhibitory effects of exercise on the protein levels of TIMP1, hypoxia-inducible factor-alpha, vascular endothelial growth factor receptor 2, vascular endothelial growth factor, and neurogenic locus notch homolog protein 1 in MCAO rats were partially reversed by OE-TIMP1. Altogether, exercise preconditioning had protective effects on CIRI by restraining TIMP1, which provided new therapeutic strategies for preventing CIRI.

Potential nephroprotective effect of dapagliflozin against renal ischemia reperfusion injury in rats via activation of autophagy pathway and inhibition of inflammation, oxidative stress and apoptosis

Renal ischemia/reperfusion injury is a common cause of acute kidney injury (AKI), causing tissue damage, inflammation and oxidative stress. Autophagy, responsible for breakdown and recycling of cytoplasmic components. In hypoxic and ischemic renal damage, autophagy may serve as a survival strategy for the cells. Dapagliflozin has been shown to have protective effects against ischemia. Objective: The study investigates the potential nephro-protective effects of dapagliflozin on renal ischemia reperfusion injury, evaluating its antioxidant, anti-inflammatory, anti-apoptotic effects and activation of autophagy via biochemical parameters and histopathological changes in adult male rats. Material and method: In this study, twenty eight male rats weighing between 200-300g, were divided into 4 groups sham, RIRI, DMSO, Dapagliflozin pretreated groups. All groups subjected to 30 min. of ischemia then 24 h of reperfusion except sham undergo the same anesthesia and surgical procedures except for bilateral renal ischemia. Dapagliflozin 1mg/kg and DMSO was given 2 hours before the induction of ischemia. Results: The study found that blood urea and serum creatinine levels increased in RIRI and DMSO groups when compared with sham group. Renal tissue levels of IL-6, Kim-1, caspase-3, LC-3 and Akt were also elevated in RIRI while GSH levels decreased in the RIRI. Dapagliflozin group showed significant increases in GSH, LC-3 and Akt levels when compared to sham group. Dapagliflozin reduced serum urea and creatinine levels, and renal tissue levels of IL-6, Kim-1, and caspase-3 also reduced. Conclusion: Dapagliflozin significantly reduced renal damage in rat model due to its antioxidant, anti-inflammatory, anti-apoptotic, and activation autophagy.

Ineffectiveness of 6,2',4'-trimethoxyflavone in mitigating cerebral ischemia/reperfusion injury after post-reperfusion administration in rats.

Pharmacological inhibition of aryl hydrocarbon receptor (AhR) activation after ischemia alleviates cerebral ischemia/reperfusion (IR) injury. To investigate whether AhR antagonist administration after reperfusion was also effective in attenuating cerebral IR injury. A total of 24 Sprague-Dawley rats were divided into the sham-operated group (no IR), control group (IR), and 6,2',4'-trimethoxyflavone (TMF) group (IR + TMF administration), with 10 rats assigned to each group. Cerebral IR injury was induced by 60 min of middle cerebral artery occlusion followed by reperfusion. TMF (5 mg/kg) was used as the AhR antagonist and was administered intraperitoneally immediately after reperfusion. Cerebral IR injury was observed using magnetic resonance imaging (MRI) and neurobehavioral assessments at baseline, immediately after ischemia, and at 3 days after ischemia. On MRI, the TMF group showed no significant differences in relative apparent diffusion coefficient (ADC), T2, and fractional anisotropy (FA) values; midline shift value; and infarct volume. In terms of neurobehavioral function, factors such as grip strength, contralateral forelimb use, time to touch, and time to remove adhesive tape from the forepaw, were also not significantly different between the control and TMF groups. This study demonstrated that AhR treatment after reperfusion had no noticeable effect on reducing cerebral IR injury in rats.

Oleuropein Relieves Pancreatic Ischemia Reperfusion Injury in Rats by Suppressing Inflammation and Oxidative Stress through HMGB1/NF-κB Pathway.

Oleuropein (OLP) is a naturally occurring phenolic compound in olive plant with antioxidant and anti-inflammatory potential and can possibly be used in treating pancreatic injuries. This investigation aimed to follow the molecular mechanism behind the potential therapeutic effect of OLP against pancreatic injury persuaded by ischemia-reperfusion (I/R). Pancreatic I/R injury was induced by splenic artery occlusion for 60 min followed by reperfusion. Oral administration of OLP (10 and 20 mg/kg) for 2 days significantly alleviated I/R-persuaded oxidative damage and inflammatory responses in pancreatic tissue as indicated by the decreased malondialdehyde (MDA) content and increased glutathione peroxidase (GPx) activity, accompanied by the suppression of myeloperoxidase (MPO) activity and reduced levels of interleukin-1beta (IL-1β), nuclear factor kappa B (NF-κB), and tumor necrosis factor alpha (TNF-α) in pancreatic tissues. Furthermore, OLP treatment markedly restored the serum levels of amylase, trypsinogen-activated peptide (TAP), and lipase, with concurrent improvement in pancreatic histopathological alterations. Moreover, treatment with OLP regulated the pancreatic expression of inducible nitric oxide synthase (iNOS) and high-mobility group box 1 (HMGB1) relative to rats of the pancreatic IR group. Thus, OLP treatment significantly alleviates the I/R-induced pancreatic injury by inhibiting oxidative stress and inflammation in rats through downregulation of HMGB1 and its downstream NF-κB signaling pathway.

A novel framework for uncovering the coordinative spectrum-effect correlation of the effective components of Yangyin Tongnao Granules on cerebral ischemia-reperfusion injury in rats

Ethnopharmacological relevanceIschemic stroke is currently a major public health hazard.Yangyin Tongnao Granules (YYTN), a traditional Chinese medicinal prescription, exerts potential therapeutic effects on subsequent cerebral ischemia-reperfusion injury (CIRI) after ischemic stroke. However, further studies are required to comprehend the underlying mechanism of YYTN for treating CIRI and the associated spectrum-effect mechanisms. Aim of the studyTo investigate the coordinated correlation between the fingerprint and the pharmacodynamic indexes of the effective components (total flavonoids, total saponins, total alkaloids, and total phenolic acids) in YYTN for treating CIRI in rats. MethodsThe fingerprints of five specific components (ligustrazine, puerarin, ferulic acid, calycosin, and formononetin) of YYTN in rats with middle cerebral artery occlusion (MCAO) were established using high-performance liquid chromatography (HPLC), and their peak areas were quantified in plasma samples. The pharmacodynamic indexes of tumor necrosis factor-alpha (TNF-α), cytochrome c (Cyt-C), and total superoxide dismutase (T-SOD) were integrated using the Criteria Importance Through Intercriteria Correlation (CRITIC) method to create a comprehensive evaluation index. Spectrum-effect correlation was analyzed by performing gray relation analysis (GRA), correlation analysis (CA), and partial least squares regression (PLSR). The Borda method was then applied to integrate the obtained results. ResultsIn MCAO rats, the effective components of YYTN reduced TNF-α and Cyt-C and increased T-SOD, which indicates their anti-inflammatory, antiapoptotic, and antioxidant effects. Spectrum-effect CA revealed certain associations between the chromatographic peaks of the five main components and the comprehensive pharmacodynamic evaluation index. Of these components, formononetin displayed the highest correlation, whereas ferulic acid exhibited the lowest correlation. All components showed a positive correlation. Using the Borda method, the components were ranked as follows based on correlation: formononetin > calycosin > ligustrazine > puerarin > ferulic acid. ConclusionsThe effective components of YYTN exhibited synergistic effects in the treatment of MCAO rats, which could potentially be attributed to their multitarget and multipathway mechanisms. The Borda method-based spectrum-effect correlation analysis provides a coordinated approach to investigate the relationship between fingerprint and pharmacodynamics of traditional Chinese medicine (TCM).

Time varying characteristic in somatosensory evoked potentials as a biomarker of spinal cord ischemic-reperfusion injury in rat.

Spinal cord ischemic-reperfusion injury (SCIRI) could occurs during surgical procedures without detection, presenting a complex course and an unfavorable prognosis. This may lead to postoperative sensory or motor dysfunction in areas innervated by the spinal cord, and in some cases, permanent paralysis. Timely detection of SCIRI and immediate waring can help surgeons implement remedial intervention to prevent irreversible spinal cord injury. Therefore, it is crucial to develop a precise and effective method for early detection of SCIRI. This study utilized rat models to simulate intraoperative SCIRI and employed somatosensory evoked potentials (SEP) for continuous monitoring during surgery. In this study, SEP signal changes were examined in six groups with varying severities of SCIRI and one normal control group. SEP signal changes were examined during operations in different groups and correlated with postoperative behavioral and histopathological data. The result demonstrated specific changes in SEP signals during SCIRI, termed as time-varying characteristics, which are associated with the duration of ischemia and subsequent reperfusion. Time-varying characteristics in SEP could potentially serve as a new biomarker for the intraoperative detection of SCIRI. This finding is significant for clinical surgeons to identify and guide early intervention of SCIRI timely. Additionally, this measurement is easily translatable to clinical application.

Investigation of preconditioning and the protective effects of nicotinamide against cerebral ischemia-reperfusion injury in rats

This study investigated the antioxidant and neuroprotective effects of nicotinamide combined with ischemic preconditioning against cerebral ischemia reperfusion (CIR) injury. Thirty-five Wistar albino male rats were randomly divided into five groups: sham, preconditioned ischemia/reperfusion (IP+IR), ischemia/reperfusion (IR), preconditioned ischemia/reperfusion + nicotinamide (IP+IR+N), and ischemia/reperfusion + nicotinamide (IR+N). CIR was achieved with bilateral common carotid artery occlusion. IP+IR and IP+IR+N groups 30 min before ischemia; Three cycles of 10 sec ischemia/30 sec reperfusion followed by 20 min IR were applied. The IP+IR+N and IR+N groups received 500 mg/kg nicotinamide intraperitoneally. After 24 h of reperfusion, a neurological evaluation was performed and vertıcal pole test. Biochemically, malondialdehyde (MDA), glutathione (GSH) levels and catalase (CAT) activity were measured in blood and brain tissue samples. Rates of red neurons, sateliosis and spongiosis were determined histopathologically in the prefrontal cortex areas.After CIR, MDA levels increased significantly in serum and brain tissue in the IR group compared to the sham group, while GSH and CAT activity decreased in the brain tissue (p < 0.05). MDA levels in the tissues were found significantly decreased in the IR+N group compared to the IR group (p < 0.05). Administration of nicotinamide together with IP significantly decreased MDA levels in brain tissue and increased GSH and CAT activity (p < 0.05). Compared to the IR group, the morphological and neurological damage in the prefrontal cortex areas decreased in the IP+IR, IP+IR+N, and IR+N groups (p < 0.05). In addition, red neuron, sateliosis and spongiosis rates increased significantly in the IR group compared to the Sham, IP+IR+N, IR+N groups (p < 0.001 for all). In neurological evaluation, while the neurological score increased and the time on the vertical pole decreased significantly in the IR group, preconditioning, and nicotinamide groups reversed (p < 0.05). The study’s results show that nicotinamide administration with ischemic preconditioning alleviates cerebral ischemia/reperfusion injury.

Protective effect of irbesartan against hepatic ischemia-reperfusion injury in rats: role of ERK, STAT3, and PPAR-γ inflammatory pathways in rats.

This study aimed to elucidate the possible hepatocellular protective role of irbesartan during hepatic ischemia-reperfusion injury (HIRI) and the probable underlying mechanisms. Wistar rats were allocated into four groups: sham; HIRI (control); irbesartan (50 mg/kg) + HIRI; irbesartan (100 mg/kg) + HIRI; irbesartan + GW9662 (1 mg/kg, i.p.) + HIRI. Rats pretreated orally with irbesartan or vehicle for 14 days underwent 45-min hepatic ischemia followed by 60-min reperfusion. Irbesartan preconditioning diminished alanine transaminase (ALT) and aspartate transaminase (AST) serum levels, and reduced extracellular signal-regulated kinase (ERK) and signal transducer and activator of transcription 3 (STAT3). Irbesartan decreased proapoptotic BAX (bcl-2-like protein 4), increased anti-apoptotic B-cell lymphoma 2 (BCL2) hepatic content, and thereby reduced BAX/BCL2 ratio. Moreover, irbesartan preconditioning reduced autophagy-related proteins Beclin1 and LC3 II, and elevated p62 (protein responsible for autophagosome degradation). It elevated proliferator-activated receptor γ (PPAR-γ), and reduced tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) hepatic gene expression. Also, hepatic protein expressions of nuclear factor kappa-B p65 (NF-κB p65) and caspase-3 were lessoned by irbesartan pretreatment in HIRI rats. However, GW9662 abrogated irbesartan's effect on HIRI. The protective effect of irbesartan on HIRI may be mediated by alleviation of ERK, STAT3, and PPAR-γ inflammatory pathways, exerting anti-apoptotic and anti-autophagic effects in HIRI in rats.

The effects and significance of Dicyclopentadiene on the expression of Intersectin-1 after cerebral ischemia-reperfusion in rats

ObjectiveThis study mainly observed the changes in Intersectin-1 (ITSN-1) expression in rat brain tissue after ischemia-reperfusion intervened by Dicyclopentadiene. MethodsSD rats were randomly divided into non-middle Cerebral Artery Occlusion model group (normal group, sham operation group) and Middle Cerebral Artery Occlusion (MCAO) model group [Ischemia reperfusion (cerebral ischemia reperfusion)] reperfusion,IR) (6h, 24h, 72h, 1w, 2w) group, butylphthalein intervention group], First of all, Use Western The expression of ITSN-1 in the cerebral tissue of infarction side after ischemia-reperfusion injury in each group was measured by blotting, and then the loss and degree of nerve function after ischemia-reperfusion injury in each group was evaluated by Zea-Longa scoring method. The morphological changes of cells in the ischemic penumbra region in the normal group and the MCAO model group for 24h were observed by HE staining. Next, 24h was selected as the reperfusion point for intervention with butylphthalein sodium chloride injection. Finally, Zea-Longa scoring method was used to evaluate whether the rats had neurological impairment and its degree, TTC (Triphenyltetrazolium chloride) staining was used to determine whether the rats had cerebral infarction and its extent, and Western The expression of ITSN-1 in the cerebral tissue of infarcted rats after ischemia-reperfusion injury was measured by blotting. Results1. Zea-Longa scoring: Scores, except for the normal group and sham operation group (which scored 0), ranged between 2.75 ± 0.46 in the ischemia-reperfusion 24h group and 1.88 ± 0.35 in the Dicyclopentadiene intervention group, showing statistically significant decreases (P<0.05). 2. HE staining results: The cell structures in the brain tissues of normal group rats were normal with regular nuclear shapes and sizes. There were no obvious abnormal changes. Rats in the ischemia-reperfusion 24h group showed obviously swollen cells, reduced and aggregated nucleus, and cell necrosis in the ischemic penumbra. 3. TTC staining results: Except for the normal group and the sham operation group, which had no infarcts, the ischemia-reperfusion 24h group had the largest volume ratio of cerebral infarction. The volume ratio of cerebral infarction in the Dicyclopentadiene intervention group relatively reduced, making a difference with statistical significance (P<0.05). 4. Western blotting results: After cerebral ischemia-reperfusion in rats, ITSN-1 expression in the infarction-side brain tissue dynamically changed. ITSN-1 expression in the ischemia-reperfusion 24h group was significantly lower among other groups compared to the normal group (P<0.05). After 24 hours, the expression gradually increased after using Dicyclopentadiene intervention, the difference was statistically significant (P<0.05). ConclusionAfter cerebral ischemia-reperfusion in rats, ITSN-1 expression dynamically changed in the infarction-side brain tissue. Dicyclopentadiene can alleviate ischemia-reperfusion injuries in rats, which might be related to the regulation of ITSN-1 expression.

Exploring the therapeutic potential of Modafinil in mitigating renal ischemia-reperfusion injury in rats.

Renal ischemia reperfusion injury (IRI) is a post-ischemic event, which can lead to subsequent acute kidney injury (AKI), transplant failure, renal dysfunction and fibrosis via heightened oxidative stress and production of inflammatory cytokines and chemokines. This study aims to assess the effect of Modafinil, a wake-promoting agent with previously proven anti-inflammatory and anti-oxidative properties, on ameliorating renal IRI. A total of 30 male Wistar rats were divided into five groups: Sham-operated group, ischemia reperfusion (I/R) control group and Modafinil pre-treated groups (at different doses of 50, 100 and 150 mg/kg). IRI was induced by means of bilaterally clamping the renal arteries for 45 min, followed by 24 h of reperfusion. Tissue pathological assessments demonstrated a reduction of glomerular, vascular and interstitial injury at doses of 50 and 100 mg/kg of Modafinil. The biochemical studies showed a significant decrease in tissue pro-inflammatory factors, including tumor necrosis factor alpha (TNF-α), Interleukin-18 (IL-18) and lactate dehydrogenase (LDH). Moreover, an elevation was observed in levels of super oxide dismutase (SOD) and catalase, indicating the reduction of oxidative stress. Furthermore, the levels of creatinine (Cr), urea and neutrophil gelatinase-associated lipocalin (NGAL) were declined, indicating the improvement in renal function at effective doses of Modafinil (50 and 100 mg/kg) compared to the I/R control group without Modafinil pre-treatment. Our findings suggest that Modafinil holds promise as an effective therapeutic agent to address the clinical challenges associated with kidney IRI reducing the need for hospitalization and potentially alleviating related morbidities.

Buyang Huanwu Decoction attenuates cerebral ischemia-reperfusion injury in rats via miR-26a-5p mediated PTEN/PI3K/Akt signaling pathway

This study aims to investigate the mechanism of Buyang Huanwu Decoction in treatment of cerebral ischemia-reperfusion injury in rats. A total of 180 SD rats were randomly divided into 5 different groups: sham group, model group, Buyang Huanwu Decoction group, Buyang Huanwu Decoction + miR-26a-5p agomir(agomir) group, Buyang Huanwu Decoction + miR-26a-5p agomir negative control(agomir NC) group. There were 36 rats in each group. Each group was then subdivided into three subgroups for the duration of reperfusion(3, 7, 14 d). A ligature-induced middle cerebral artery occlusion(MCAO) model was carried out on all groups other than sham group. Reperfusion was performed following ischemia for 90 min. Buyang Huanwu Decoction group, agomir group, and agomir NC group were given Buyang Huanwu Decoction twice daily by gavage 24 h after the formation of the model. Sham group and model group were given an equal amount of physiological saline by gavage until the day before sacrifice. At 24 h after ischemia induction, miR-26a-5p agomir was injected into the lateral ventricle in agomir group, miR-26a-5p NC in agomir NC group, and equal amounts of physiological saline in the other groups. 24 h after ischemia induction, BrdU was intraperitoneally injected once daily until the day before sacrifice. Modified neurological severity score(mNSS) was used to evaluate neurological deficits, 2,3,5-triphenyltetrazolium chloride(TTC) staining was used to determine the cerebral infarct volume, TUNEL staining was used to assess the apoptosis of parenchymal ischemic brain tissue, and double immunofluorescence staining was used to examine BrdU/NeuN double positive neurons in the parenchymal ischemic brain tissue to evaluate the neuronal regeneration. We employed a luciferase reporter assay to identify and validate that the target gene of miR-26a-5p is PTEN. Real-time quantitative polymerase chain reaction(RT-qPCR) was used to assess gene expression levels of PTEN and miR-26a-5p and Western blot to assess the protein levels of PTEN, PI3K, p-PI3K, Akt, and p-Akt. The results revealed that compared with model group, Buyang Huanwu Decoction treatment promoted neural function recovery, reduced the cerebral infarct volume, increased the number of BrdU~+/NeuN~+ neurons, upregulated the expression of miR-26a-5p, regulated the PTEN/PI3K/Akt signaling pathway, and promoted neuronal regeneration in the cerebral ischemia-reperfusion rats. These effects were significantly enhanced after lateral ventricle injection of miR-26a-5p agomir. The findings prove that Buyang Huanwu Decoction treatment can promote neural function recovery, reduce the cerebral infarct volume, and promote neuronal regeneration in a cerebral ischemia-reperfusion rat model, which is likely to be achieved via miR-26a-5p mediated PTEN/PI3K/Akt signaling pathway.

ISL1-overexpressing BMSCs attenuate renal ischemia-reperfusion injury by suppressing apoptosis and oxidative stress through the paracrine action

Ischemia-reperfusion injury (IRI) is a major event in renal transplantation, leading to adverse outcomes. Bone marrow mesenchymal stem cells (BMSCs) are novel promising therapeutics for repairing kidney injuries. The therapeutic efficacy of BMSCs with ISL1 overexpression in renal IRI and its underlying mechanism need to be investigated. The unilateral renal IRI rat model was established to mimic clinical acute kidney injury. Rats were injected with PBS, BMSCs-Scrambled or BMSCs-ISL1 via the tail vein at the timepoint of reperfusion, and then sacrificed after 24 h of reperfusion. The administration of BMSCs-ISL1 significantly improved renal function, inhibited tubular cells apoptosis, inflammation, oxidative stress in rats. In vitro, HKC cells subjected to H2O2 stimulation were pretreated with the conditioned medium (CM) of BMSCs-Scrambled or BMSCs-ISL1. The pretreatment of ISL1-CM attenuated apoptosis and oxidative stress induced by H2O2 in HKC cells. Our proteomic data suggested that haptoglobin (Hp) was one of the secretory proteins in ISL1-CM. Subsequent experiments confirmed that Hp was the important paracrine factor from BMSCs-ISL1 that exerted anti-apoptotic and antioxidant functions. Mechanistically, Hp played a cytoprotective role via the inhibition of ERK signaling pathway, which could be abrogated by Ro 67-7476, the ERK phosphorylation agonist. The results suggested that paracrine action may be the main mechanism for BMSCs-ISL1 to exert protective effects. As an important anti-apoptotic and antioxidant factor in ISL1-CM, Hp may serve as a new therapeutic agent for treating IRI, providing new insights for overcoming the long-term adverse effects of stem cell therapy.

Outcomes of oxytocin treatment on intestinal ischemia-reperfusion injury in rats

Ischemia-reperfusion injury is a clinical condition that poses life-threatening risks and can be caused by diseases or operations such as trauma, shock, and gastric dilatation volvulus. The objective of this study was to examine the effect of oxytocin on intestinal damage in rats induced by experimental ischemia-reperfusion injury. Three groups of Wistar albino rats were established: a control group (CTR, n=6), an intestinal ischemia-reperfusion group (I-IR, n=6), and an intestinal ischemia-reperfusion with oxytocin group (I-IR+Oxt, n=6). The I-IR+Oxt group received an intraperitoneal injection of 1 mg/kg oxytocin 30 minutes before anesthesia. In the I-IR and I-IR+Oxt groups, the superior mesenteric artery was ligated for 1 hour to induce ischemia-reperfusion injury, followed by one hour of reperfusion by opening the ligatures. At the end of the reperfusion period, the rats were euthanized, and blood and intestinal tissue samples were collected. From the blood samples, ALT, ALP, AST, LDH, BUN, creatinine, IL-1β, and TNF-α concentrations were evaluated. Tissue samples were analyzed for IL-1β, TNF-α, and MDA activity. Serum and tissue IL-1β and TNF-α concentrations were higher in both the I-IR and I-IR+Oxt groups compared to the CTR group. However, these levels were found to be lower in the I-IR+Oxt group compared to the I-IR group. The histopathological analysis showed that the I-IR+Oxt group had better epithelial regeneration and less inflammatory cell infiltration compared to the I-I/R group. In conclusion, oxytocin inhibited the release of IL-1β and TNF-α and the harmful effect of I/R on intestinal cells.

Syringic acid loaded silver nanoparticles protects ovarian ischemia-reperfusion injury in rats by inhibiting endoplasmic reticulum stress-mediated apoptosis

In the present study, we investigated the protective effect of syringic acid (SA) loaded silver nanoparticles (AgNPs) on endoplasmic reticulum stress-mediated apoptosis during ovarian ischemia-reperfusion injury (IR) in rats. Initial UV–Vis and FT-IR analysis revealed the presence of the Ag and SA in the SA-AgNPs, respectively. TEM analysis demonstrated the spherical morphology with 10–50 nm of nanoparticle size. Next, we evaluated the protective effect of SA-AgNPs against IR. 15-weeks-old rats were divided into seven groups, as follows: control, AgNPs, SA, IR, AgNPs + IR, SA + IR, and SA + AgNPs + IR. Induction of IR led to a significant increase in apoptotic markers (caspase-3), pro-inflammatory markers (IL-1β, TNF-α, ATF-6, NF- κB-p65, and P2X7R), and endoplasmic reticulum stress marker (IRE1) in ovary tissue. Additionally, a remarkable increase in serum IL-1β and TNF-α were found. Moreover, an increase in serum MDA and decreased endogenous anti-oxidant enzymes, including GSH and SOD were observed. Interestingly, treatment with either AgNPs or SA significantly reduced apoptosis, inflammation, and ER stress markers in IR-induced rats. Nevertheless, discernible effects were detected in rats upon treatment with SA + AgNPs. These findings strongly suggest that syringic acid-loaded silver nanoparticles have a promising therapeutic application in ovarian ischemia-reperfusion (IR) injury.

RNA sequencing reveals the potential mechanism of exercise preconditioning for cerebral ischemia reperfusion injury in rats.

Cerebral ischemia reperfusion injury (CIRI) often leads to deleterious complications after stroke patients receive reperfusion therapy. Exercise preconditioning (EP) has been reported to facilitate brain function recovery. We aim to explore the specific mechanism of EP in CIRI. Sprague-Dawley rats were randomized into Sham, middle cerebral artery occlusion (MCAO), and EP groups (n=11). The rats in the EP group received adaptive training for 3 days (10m/min, 20min/day, with a 0° incline) and formal training for 3 weeks (6 days/week, 25m/min, 30min/day, with a 0° incline). Then, rats underwent MCAO surgery to establish CIRI models. After 48h, neurological deficits and cerebral infarction of the rats were measured. Neuronal death and apoptosis in the cerebral cortices were detected. Furthermore, RNA sequencing was conducted to investigate the specific mechanism of EP on CIRI, and qPCR and Western blotting were further applied to confirm RNA sequencing results. EP improved neurological deficit scores and reduced cerebral infarction in MCAO rats. Additionally, pre-ischemic exercise also alleviated neuronal death and apoptosis of the cerebral cortices in MCAO rats. Importantly, 17 differentially expressed genes (DEGs) were identified through RNA sequencing, and these DEGs were mainly enriched in the HIF-1 pathway, cellular senescence, proteoglycans in cancer, and so on. qPCR and Western blotting further confirmed that EP could suppress TIMP1, SOCS3, ANGPTL4, CDO1, and SERPINE1 expressions in MCAO rats. EP can improve CIRI in vivo, the mechanism may relate to TIMP1 expression and HIF-1 pathway, which provided novel targets for CIRI treatment.

The use of ultrasound for noninvasive monitoring of anesthetic effects in renal ischemia-reperfusion injury.

Compared with the use of ultrasound for noninvasive monitoring of the anesthetic sodium pentobarbital versus tribromoethanol in an animal model of renal ischemia-reperfusion injury in rats. Adult rats were randomly assigned to a renal ischemia-reperfusion injury model, and preoperative anesthetics were administered as either sodium pentobarbital or tribromoethanol. Color Doppler ultrasound and spectral Doppler ultrasound were used to detect changes in respiratory rate and heart rate during and after the surgery, as well as measure renal hemodynamic parameters including peak systolic velocity, end-diastolic velocity, and resistance index. The frequency of changes in respiration and heart rate was significantly higher in the sodium pentobarbital anesthesia group compared to the tribromoethanol anesthesia group. The peak systolic velocity and end-diastolic velocity values in the sodium pentobarbital anesthesia group were significantly lower than those in the tribromoethanol group. However, the resistance index in the sodium pentobarbital group was higher than that in the tribromoethanol group. Ultrasound can be used to dynamically monitor the effects of anesthesia during the experiment, including changes in respiratory rate and heart rate, as well as semi-quantitatively monitor hemodynamic changes in the kidneys, which indirectly reflects whole-body hemodynamic changes in rats.

Effects of ultrashort wave on neuronal damage and heat shock protein 70 expression after cerebral ischemia-reperfusion injury in rats

BackgroundUltrashort wave (USW) therapy has been reported to alleviate cerebral ischemia/reperfusion (IR) injury, however the underlying mechanisms remain elusive. The aim of this study was to observe the effect of non-thermal USW therapy on neuronal damage and expression of heat shock protein 70 (HSP70) after cerebral IR in rats. MethodsFocal ischemia-reperfusion (IR) was induced in Sprague–Dawley rats by middle cerebral artery occlusion/reperfusion (MCAO/R). The Ninety-two rats (both male and female) were screened using the Zea-Longa 5 grade evaluation. Included rats were then randomly divided into blank, sham, model 1-day, model 3-day, model 7-day, USW 1-day, USW 3-day, or USW 7-day groups. All rats in the model groups received sham USW treatment, while rats in the USW groups received USW treatment, for 1, 3, or 7 days. We assessed the National Institutes of Health Stroke Scale, brain infarction volumes, ultrastructural damage scores using electron microscopy, and HSP70 expression by western blotting between the different groups. ResultsUSW treatment reduced the National Institutes of Health Stroke Scale, infarction volume, and ultrastructural neuronal damage, and increased expression of HSP70, in the hippocampal CA1 region. ConclusionsNon-thermal USW therapy may improve neurological function, decrease infarction volume, and reduce neuronal damage by increasing HSP70 expression following cerebral IR injury.

Anti-oxidative and anti-inflammatory effects of Ginkgo biloba extract (EGb761) on hindlimb skeletal muscle ischemia-reperfusion injury in rats.

In posterior spine surgery, retractors exert pressure on paraspinal muscles, elevating intramuscular pressure and compromising blood flow, potentially causing muscle injury during ischemia-reperfusion. Ginkgo biloba extract (EGb 761), known for its antioxidant and free radical scavenging properties and its role in treating cerebrovascular diseases, is investigated for its protective effects against muscle ischemia-reperfusion injury invitro and invivo. Animals were randomly divided into the control group, receiving normal saline, and experimental groups, receiving varying doses of EGb761 (25/50/100/200 mg/kg). A 2-h hind limb tourniquet-induced ischemia was followed by reperfusion. Blood samples collected pre-ischemia and 24 h post-reperfusion, along with muscle tissue samples after 24 h, demonstrated that EGb761 at 1000 μg/mL effectively inhibited IL-6 and TNF-α secretion in RAW 264.7 cells without cytotoxicity. EGb761 significantly reduced nitric oxide (NO) and malondialdehyde (MDA) levels, myeloperoxidase (MPO) activity, and increased glutathione (GSH) levels compared to the control after 24 h. Muscle tissue sections revealed more severe damage in the control group, indicating EGb761's potential in mitigating inflammatory responses and oxidative stress during ischemia-reperfusion injury, effectively protecting against muscle damage.

Synergistic effect of chrysin and kaempferol in ameliorating Cerebral Ischemic Reperfusion injury in rat by controlling expression of proinflammatory mediators NF-κB and STAT3

ABSTRACT Objectives The two flavonoids kaempferol and chrysin are known to possess anti-inflammatory and antioxidant activities. In addition, these two flavonoids were reported to display synergistic effects against inflammation. The present study aims to provide an analysis of the combined effects of kaempferol and chrysin on ischemic rat brain induced by endothelin-1. Methods The neurological deficit score and infarct area of the brain were determined post drug treatment. Histopathological sections displayed the morphological changes in the brain tissue. The brain tissues were processed for assessing the antioxidant and anti-inflammatory activity by measuring superoxide dismutase activity, catalase activity, level of reduced glutathione, brain malondialdehyde, and amount of calcium. The expression level of inflammatory molecules was analyzed by western blotting and immunohistochemistry. Results The infarct area, neurological score and NF-κB and STAT3 expression levels were significantly reduced. Discussion The analysis of neuroprotective synergistic activity of kaempferol and chrysin indicated the therapeutic potential of the combination in alleviating cerebral ischemia by controlling expression of proinflammatory mediators.