Rat Tissues Research Articles

Determination of tissue distribution of VX and its metabolites EMPA and EA-2192 in various rat tissues by LC-ESI-MS/MS after phosphotriesterase treatment

Phosphotriesterases (PTE) are a new and promising approach for the treatment of organophosphate poisoning, since the current therapy of such intoxications shows some limitations. A previous rat in vivo study confirmed the therapeutic effect of PTE, which were specifically designed for VX breakdown, and demonstrated rapid degradation of VX in whole blood samples. The present study now focuses on the degradation of VX and its distribution in organ tissues of the animals used in the aforementioned study. In order to gain a broader overview, we have extended the investigations to the VX metabolites EA-2192 and EMPA by using methods developed for an LC-ESI-MS/MS system. Applying these methods, we were able to verify the effectiveness of the PTE treatment and gained an overview of VX tissue distribution in poisoned but untreated rats.

Enhancing anti-calcification efficacy in veterinary cardiovascular surgeries: evaluating short-term ethanol’s role in glutaraldehyde fixed pericardial tissues in rats

Enhancing anti-calcification efficacy in veterinary cardiovascular surgeries: evaluating short-term ethanol’s role in glutaraldehyde fixed pericardial tissues in rats

The effects of PPARγ agonists on long‑termpotentiation and apoptosis in the hippocampusarea of juvenile hypothyroid rats

The aim of the present study was to evaluate the effect of rosiglitazone (RSG) or pioglitazone (POG) on the synaptic plasticity, neuronal apoptosis, brain-derived neurotrophic factor (BDNF), and nitric oxide (NO) metabolites in the hippocampus of juvenile hypothyroid rats. The animals were divided into four groups: control; propylthiouracil (PTU), 0.05% dose in drinking water for 42 days; PTU–POG; and PTU–RSG. The POG (20 mg/kg) and the RSG (4 mg/kg) were administered by IP injection. We conducted long‑term potentiation (LTP) in the cornu ammonis 1 area of the hippocampus using high‑frequency stimulation of the Schaffer collateral pathway. Then, the hippocampal tissues were collected to determine BDNF and NO levels and the degree of apoptosis. PTU administration decreased the slope (10–90%) and amplitude of the fEPSPs compared to control. Injection of RSG or POG increased the slope, slope (10–90%), and amplitude of the fEPSP in the PTU‑POG or PTU‑RSG groups compared to the PTU group. TUNEL‑positive neurons and NO metabolites in the hippocampus of the PTU group were higher than those of the control group. RSG or POG increased BDNF content in PTU–POG or PTU–RSG groups. Treatment of the rats with POG or RSG decreased apoptotic neurons and NO metabolites in the hippocampus of PTU–POG or PTU–RSG groups, respectively, compared to the PTU group. This study’s results revealed that POG or RSG normalized LTP impairment, neuronal apoptosis, and improved BDNF content in the hippocampal tissue of juvenile hypothyroid rats.

Effect of moxibustion at "Xinshu" (BL15) and "Feishu" (BL13) on expression of TRPV1 and CGRP in the myocardial tissue of chronic heart failure rats.

To observe the effect of moxibustion at "Xinshu" (BL15) and "Feishu" (BL13) on transient receptor potential vanilloid type 1(TRPV1), calcitonin gene-related peptide (CGRP), and serum interleukin-10 (IL-10) in the myocardial tissue of rats with chronic heart failure (CHF), so as to explore its underlying mechanisms in improvement of CHF. Male SD rats were randomly divided into the normal, model, moxibustion, capsaicin, moxibustion + capsaicin, and moxibustion + solvent groups, with 10 rats in each group. The CHF model was established by permanent ligation of the anterior descending branch of the left coronary artery. Mild moxibustion was applied to bilateral BL13 and BL15 for 30 min once daily for 4 weeks. Rats in the capsaicin group were smeared with capsaicin in the acupoint area once a day for 4 weeks. For rats of the moxibustion + capsaicin and moxibustion + solvent groups, capsaicin and solvent were applied to the acupoint area before moxibustion for 4 weeks, respectively. The ejection fraction (EF) and left ventricular fractional shortening rate (FS) were examined by echocardiography. HE staining was used to observe the myecardial morphological structure. The mRNA and protein expression levels of TRPV1, CGRP and galectin-3 (Gal-3) in myocardial tissue were detected by real-time quantitative PCR and Western blot, respectively. The content of IL-10 in serum was detected by ELISA. After modeling, the pathological changes of myocardium (as cardiac muscle fiber disorder, inflammatory cell infiltration, etc.) were obvious, and the EF, FS, serum IL-10, protein and mRNA exspression of TRPV1 and CGRP were significantly decreased (P<0.01) in the model group compared with the normal group, while the protein and mRNA exspression of Gal-3 were significantly up-regulated (P<0.01). Following the interventions, the above-mentioned indexes were all reversed in moxibustion, capsaicin, and moxibustion + capsaicin groups (P<0.01), and the effect of moxibustion + capsaicin was the best (P<0.05, P<0.01). Moxibustion can reduce myocardial injury and improve cardiac function in CHF rats, which may be related to its effects in up-regulating the expression of TRPV1 and CGRP, and down-regulating the expression of Gal-3 to alleviate myocardial fibrosis.

Effect of ß- Caryophyllene on Urocortin-3 expression in adipose tissue of high fat diet and fructose-induced type-2 diabetic rats

Effect of ß- Caryophyllene on Urocortin-3 expression in adipose tissue of high fat diet and fructose-induced type-2 diabetic rats

PLK-3-mediated phosphorylation of BAP1 prevents diabetic retinopathy

Diabetic retinopathy (DR) is a microvascular complication of diabetes mellitus, and its main clinical manifestation is retinal vascular dysfunction. DR causes blindness and is a problem with significant global health implications. However, treating DR is still challenging. In this study, we aimed to explore the role of polo-like kinase-3 (PLK-3) and the potential regulatory mechanism in DR. Sprague-Dawley rats were injected intraperitoneally with streptozotocin (STZ, 60 mg/kg) to induce a rat model of DR, and rat retinal microvascular endothelial cells (RRMECs) were treated with high glucose (HG, 25 mmol/L glucose) to develop a cell model of DR. We found that PLK-3 was significantly downregulated in the retinal tissues of STZ-induced diabetic rats and HG-induced RRMECs. Lentivirus-mediated PLK-3 overexpression alleviated the histological damages in DR rats. After HG stimulation, cell proliferation, migration, and angiogenesis in RRMECs were inhibited after PLK-3 upregulation. By using label-free proteomics, we identified 82 differentially expressed proteins downstream of PLK-3, including BRCA1-associated protein 1 (BAP1), which was significantly upregulated in PLK-3-overexpressed RRMECs compared to control cells under the HG condition. In vivo and in vitro assays indicated that the forced expression of PLK-3 increased the phosphorylation of BAP1 at serine 592 and caspase-8 expression. Detailed evidence showed that BAP1-shRNA-mediated knockdown restored the cell function in HG-treated RRMECs when PLK-3 was overexpressed. Collectively, this study shows that PLK-3 alleviates retinal vascular dysfunction in DR by inhibiting the phosphorylation of BAP1. Thus, PLK-3 may develop as a promising target for the therapy of DR.

Improved Preservation of Rat Small Intestine Transplantation Graft by Introduction of Mesenchymal Stem Cell-Secreted Fractions.

Segmental grafts from living donors have advantages over grafts from deceased donors when used for small intestine transplantation. However, storage time for small intestine grafts can be extremely short and optimal graft preservation conditions for short-term storage remain undetermined. Secreted factors from mesenchymal stem cells (MSCs) that allow direct activation of preserved small intestine grafts. Freshly excised Luc-Tg LEW rat tissues were incubated in preservation solutions containing MSC-conditioned medium (MSC-CM). Preserved Luc-Tg rat-derived grafts were then transplanted to wild-type recipients, after which survival, injury score, and tight junction protein expression were examined. Luminance for each graft was determined using in vivo imaging. The findings indicated that 30-100 and 3-10kDa fractions of MSC-CM have superior activating effects for small intestine preservation. Expression of the tight-junction proteins claudin-3, and zonula occludens-1 preserved for 24h in University of Wisconsin (UW) solution containing MSC-CM with 50-100kDa, as shown by immunostaining, also indicated effectiveness. Reflecting the improved graft preservation, MSC-CM preloading of grafts increased survival rate from 0% to 87%. This is the first report of successful transplantation of small intestine grafts preserved for more than 24h using a rodent model to evaluate graft preservation conditions that mimic clinical conditions.

Transcriptomic profiling highlights cell proliferation in the progression of experimental pulmonary hypertension in rats

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by pulmonary vascular remolding and occlusion, leading to the elevated pulmonary arterial pressures, right ventricular hypertrophy, and eventual heart failure if left untreated. Understanding the molecular mechanisms underlying the development and progression of pulmonary hypertension (PH) is crucial for devising efficient therapeutic approaches for the disease. Lung homogenates were collected weekly and underwent RNA-sequencing in the monocrotaline (MCT)-induced PH rat model to explore genes associated with PH progression. Statistical analyses revealed 1038, 1244, and 3125 significantly altered genes (P < 0.05, abs (log2fold change) > log21.5) between control and MCT-exposed rats during the first, second, and third week, respectively. Pathway enrichment analyses revealed involvement of cell cycle and innate immune system for the upregulated genes, GPCR and VEGF signaling for the downregulated genes. Furthermore, qRT-PCR validated upregulation of representative genes associated with cell cycle including Cdc25c (cell division cycle 25C), Cdc45, Top2a (topoisomerase IIα), Ccna2 (cyclin A2) and Ccnb1 (cyclin B1). Western blot and immunofluorescence analysis confirmed increases in PCNA, Ccna2, Top2a, along with other proliferation markers in the lung tissue of MCT-treated rats. In summary, RNA sequencing data highlights the significance of cell proliferation in progression of rodent PH.

Histological and biochemical evaluation of &lt;i&gt;Juglans regia&lt;/i&gt; L (Walnut) as potential remedial properties on the lungs and liver tissues of albino rats pre-treated with methotrexate

Histological and biochemical evaluation of &lt;i&gt;Juglans regia&lt;/i&gt; L (Walnut) as potential remedial properties on the lungs and liver tissues of albino rats pre-treated with methotrexate

Histopathological evaluation of ulcerative colitis induced by white vinegar in albino rats

The ulcerative colitis (UC) is an inflammatory bowel illness which causes persistent inflammation of the colon's innermost layers. A prominent characteristic of ulcerative colitis (UC) is the stool's blood and mucous contents. This study determined to investigate the effects of white vinegar (WV) on colon tissues in rats. Two groups of twenty rats were created; the primary group was a control, healthy group, and the WV was administered to the second group at a dose of [1 ml/kg (5%)] via orally gavage for two weeks. Findings revealed the emergence of histopathological alterations like mucosal erosions, ulceration, loss of normal architecture, mucosal atrophy, and hemorrhage; numerous crypts have inflammatory cells that entered them, blood vessels are dilated and oedema, the serosa is destroyed, which demonstrates the devastation of the mucosal lining destruction with goblet cell hyperplasia, focal necrosis of epithelium with demolished connective tissues, accumulation of inflammatory cells in the mucosa, lamina propria, and muscularis mucosa, as well as submucosal oedema when compared with the control rats. The PAS-reaction histochemical analysis showed that the treated rats had lower levels of carbohydrates than the control animals. The findings of the study demonstrated that white vinegar was a dangerous substance linked to histological alterations that resulted in acute ulcerative colitis when used daily for two weeks.

Biochemical and Histological Effects of Moringa oleifera Extract against Valproate-Induced Kidney Damage.

Valproic acid is an effective treatment for generalized seizure and related neurological defects. Despite its efficacy and acceptability, its use is associated with adverse drug effects. Moringa oleifera leaves are rich in phytochemical and nutritional components. It has excellent antioxidant and ethnobotanical benefits, thus popular among folk medicines and nutraceuticals. In the present study, 70% ethanol extract of moringa leaves was assessed for its invivo biochemical and histological effects against valproate-induced kidney damage. Female Sprague-Dawley rats were randomly divided into four groups: Group I: control animals given physiological saline (n = 8); Group II: Moringa extract-administered group (0.3 g/kg b.w./day, n = 8); Group III: valproate-administered animals (0.5 g/kg b.w./day, n = 15); and Group IV: valproate + moringa extract (given similar doses of both valproate and moringa extract, n = 12) administered group. Treatments were administered orally for 15 days, the animals were fasted overnight, anesthetized, and then tissue samples harvested. In the valproate-administered experimental group, serum urea and uric acid were elevated. In the kidney tissue of the valproate rats, glutathione was depleted, antioxidant enzyme activities (superoxide dismutase, catalase, glutathione reductase, glutathione S-transferase, and glutathione peroxidase) disrupted, while oxidative stress biomarker, inflammatory proteins (Tumor necrosis factor-alpha and interleukin-6), histological damage scores, and the number of PCNA-positive cells were elevated. M. oleifera attenuated all these biochemical defects through its plethora of diverse antioxidant and therapeutic properties.

ARRB1 inhibits extracellular matrix degradation and apoptosis of nucleus pulposus cells by promoting autophagy and attenuates intervertebral disc degeneration

ObjectiveIntervertebral disc degeneration (IVDD) is the leading cause of lower back pain (LBP). β-arrestin 1 (ARRB1) is a multifunctional protein that regulates numerous pathological processes. The aim of this study was to investigate the role of ARRB1 in IVDD. MethodsThe expression of ARRB1 in nucleus pulposus (NP) of rats with IVDD was assayed. Next, rat nucleus pulposus cells (NPCs) were infected with lentiviruses containing shArrb1 (LV-shArrb1) and overexpressing Arrb1 (LV-oeArrb1). The roles of Arrb1 in serum-deprived NPCs were investigated by measuring apoptosis, extracellular matrix degradation, and autophagic flux. For experiments in vivo, LV-oeArrb1 lentivirus was injected into the NP tissues of IVDD rats to evaluate the effects of Arrb1 overexpression on NP. ResultsIn the NP tissues of IVDD rats, ARRB1 and cleaved caspase-3 expression increased, and the ratio of LC3II/LC3I protein expression was upregulated. Arrb1 knockdown aggravated extracellular matrix degradation, cellular apoptosis, and impairment of autophagic flux in rat NPCs under serum-deprived conditions, whereas Arrb1 overexpression significantly reversed these effects. ARRB1 interacted with Beclin 1, and Arrb1 knockdown suppressed the formation of the Beclin1-PIK3C3 core complex. The autophagy inhibitor 3-methyladenine (3-MA) offset the protective effects of Arrb1 overexpression in serum-deprived NPCs. Furthermore, Arrb1 overexpression inhibited apoptosis and extracellular matrix degradation, promoted autophagy in NP, and delayed the development of IVDD in rats. ConclusionARRB1 prevents extracellular matrix degradation and apoptosis of NPCs by upregulating autophagy and ameliorating IVDD progression, presenting an innovative strategy for the treatment of IVDD.

Involvement of oxidative stress-AMPK-Cx43-NLRP3 pathway in extracellular matrix remodeling of gastric smooth muscle cells in rats with diabetic gastroparesis.

This study aimed to investigate the changes in oxidative stress, adenosine monophosphate-activated protein kinase (AMPK), connexin43 (Cx43), nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) expression, and extracellular matrix (ECM) in the gastric smooth muscle tissues of rats with diabetic gastroparesis (DGP) and high glucose-cultured gastric smooth muscle cells, determine the existence of oxidative stress-AMPK-Cx43-NLRP3 pathway under high glucose condition, and the involvement of this pathway in ECM remodeling in DGP rats. The results showed that with increasing duration of diabetes, oxidation stress levels gradually increased, the AMPK activity decreased first and then increased, NLRP3, CX43 expression, and membrane/cytoplasmratio of Cx43 expression were increased in the gastric smooth muscle tissues of diabetic rats. Changes in ECM of gastric smooth muscle cells wereobserved in DGP rats. The DGP group showed higher collagen type I content, increased expression of Caspase-1, transforming growth factor-beta 3 (TGF-β3), and matrix metalloproteinase-2 (MMP-2), decreased tissue inhibitor of metalloproteinase-1 (TIMP-1) expression, and higher interleukin-1betacontent when compared with the control group. For gastric smooth muscle cells cultured under higher glucose, the MMP-2 and TGF-β3 expression wasdecreased, TGF-β1 and TIMP-1 expression was increased, the interleukin-1betacontent was decreased in cells after inhibition of NLRP3 expression; the NLRP3 and Caspase-1expression was decreased, and adenosine triphosphate content was lower after inhibition of Cx43; the expression of NLRP3, Caspase-1, P2X7, and the membrane/cytoplasm ratio of CX43 expression was decreased in cells after inhibition of AMPK and oxidative stress, the phospho-AMPK expression was also decreased after suppressing oxidative stress. Our findings suggest that high glucose induced the activation of the AMPK-Cx43-NLRP3 pathway through oxidative stress, and this pathway was involved in the ECM remodeling of gastric smooth muscles in DGP rats by regulating the biological functions of TGF-β3, TGF-β1, MMP-2, and TIMP-1.

Detection of miR-203 expression using a nanofluorescent probe to study the neuroprotective effect of sevoflurane in a neuroinflammatory injury rat model

Ischemic cerebrovascular disease has high disability and mortality rates that can result in related sequelae if not treated promptly and properly. Nanofluorescent probes are useful in the early diagnosis of the disease due to their high sensitivity and specificity, thus facilitating early therapeutic measures and observation of disease progression. Here, a novel nanostructure probe was designed to detect the expression of miR-203 in a cerebral ischemia-reperfusion injury (CIRI) model after sevoflurane treatment, and the effects of sevoflurane and neuroinflammatory injury were discussed. A CIRI rat model was established to study miR-203 expression, nerve injury, oxidative stress, and inflammatory factors in the brain tissue of rats treated with sevoflurane. The nanofluorescent probe showed high specificity and sensitivity for miR-203 detection. miR-203 was over-expressed in CIRI rats, which was decreased by sevoflurane treatment. In addition, sevoflurane treatment significantly improved neurological function, learning, and memory in CIRI rats; decreased malondialdehyde, lactate dehydrogenase, and superoxide dismutase levels; and inhibited the expression of tumor necrosis factor α and interleukins 1 and 6. Moreover, an inverse correlation was determined between miR-203 expression and the degree of neuroinflammation. This study demonstrated that miR-203 may be a useful diagnostic and prognostic index for neuroinflammatory injury.

Staphylococcal enterotoxin B exposed to pregnant rats inhibits the hedgehog signaling pathway in thymic T lymphocytes of the offspring

The Hedgehog (Hh) signaling pathway is involved in T cell differentiation and development and plays a major regulatory part in different stages of T cell development. A previous study by us suggested that prenatal exposure to staphylococcal enterotoxin B (SEB) changed the percentages of T cell subpopulation in the offspring thymus. However, it is unclear whether prenatal SEB exposure impacts the Hh signaling pathway in thymic T cells. In the present study, pregnant rats at gestational day 16 were intravenously injected once with 15 μg SEB, and the thymi of both neonatal and adult offspring rats were aseptically acquired to scrutinize the effects of SEB on the Hh signaling pathway. It firstly found that prenatal SEB exposure clearly caused the increased expression of Shh and Dhh ligands of the Hh signaling pathway in thymus tissue of both neonatal and adult offspring rats, but significantly decreased the expression levels of membrane receptors of Ptch1 and Smo, transcription factor Gli1, as well as target genes of CyclinD1, C-myc, and N-myc in Hh signaling pathway of thymic T cells. These data suggest that prenatal SEB exposure inhibits the Hh signaling pathway in thymic T lymphocytes of the neonatal offspring, and this effect can be maintained in adult offspring via the imprinting effect.

Changes of m6A Regulatory Proteins and Nrf2 Signaling Molecules in Liver Tissue of Type 2 Diabetes Mellitus Rats.

Both dysregulation of N6-methyladenosine (m6A) regulatory proteins and Nrf2 signaling molecules are involved in the process of injury to multiple tissues. However, changes of m6A regulatory proteins and Nrf2 signaling molecules in liver tissue of T2DM remain unclear. In present study, changes of m6A regulatory proteins (Mettl3, Mettl16, Fto, Alkbh5 and Ythdc2) and Nrf2 signaling molecules (Nrf2, Sod1, Ho-1, Gclc) were detected in the liver tissues of T2DM rats, which constructed by high fat-diet feeding and intraperitoneal injection of streptozotocin. Our results indicated that the morphology of liver tissues from T2DM rats showed obvious abnormalities, as well as levels of liver function indicators and expressions of Nrf2 signaling molecules Nrf2, Sod1, Ho-1 were significantly increased in T2DM rats when compared with those in corresponding control rats. More importantly, m6A regulatory proteins such as Mettl3, Mettl16, Fto, Alkbh5 and Ythdc2 were dramatically higher than those in control rat. In a word, m6A regulatory proteins and Nrf2 signaling molecules may significantly change in liver tissue of T2DM rats. And This provides clues and ideas for the study of liver injury in T2DM from the perspective of RNA epigenetics in the future.

Effect of Resveratrol and Curcumin on Changes in Fatty Acid Composition and Oxidative Stress in Liver and Kidney Tissues of Rats Exposed to 7,12-Dimethylbenz[a]anthracene (DMBA)

Effect of Resveratrol and Curcumin on Changes in Fatty Acid Composition and Oxidative Stress in Liver and Kidney Tissues of Rats Exposed to 7,12-Dimethylbenz[a]anthracene (DMBA)

High-Throughput Proteomics and Phosphoproteomics of Rat Tissues Using Microflow Zeno SWATH.

High-throughput tissue proteomics has great potential in the advancement of precision medicine. Here, we investigated the combined sensitivity of trap-elute microflow liquid chromatography with a ZenoTOF for DIA proteomics and phosphoproteomics. Method optimization was conducted on HEK293T cell lines to determine the optimal variable window size, MS2 accumulation time and gradient length. The ZenoTOF 7600 was then compared to the previous generation TripleTOF 6600 using eight rat organs, finding up to 23% more proteins using a fifth of the sample load and a third of the instrument time. Spectral reference libraries generated from Zeno SWATH data in FragPipe (MSFragger-DIA/DIA-NN) contained 4 times more fragment ions than the DIA-NN only library and quantified more proteins. Replicate single-shot phosphopeptide enrichments of 50-100 μg of rat tryptic peptide were analyzed by microflow HPLC using Zeno SWATH without fractionation. Using Spectronaut we quantified a shallow phosphoproteome containing 1000-3000 phosphoprecursors per organ. Promisingly, clear hierarchical clustering of organs was observed with high Pearson correlation coefficients >0.95 between replicate enrichments and median CV of 20%. The combined sensitivity of microflow HPLC with Zeno SWATH allows for the high-throughput quantitation of an extensive proteome and shallow phosphoproteome from small tissue samples.

Cedrol alleviates postmenopausal osteoporosis in rats through inhibiting the activation of the NF-κB signaling pathway.

Pharmacological studies have shown that Cedrol (CE) exhibits extensive biological activities, including anti-inflammatory and analgesic. Moreover, it can inhibit the NF-κB pathway and the expression of various associated proteins. This study aimed to investigate the role of CE in postmenopausal osteoporosis. The results showed that intragastric administration of CE (10 and 20mg/kg) significantly improved the bone microstructure damage and increased bone mineral density, trabecular bone volume, and bone trabecular thickness in ovariectomized (OVX) rats (p < 0.05). CE treatment additionally made a well-organized arrangement of bone trabeculae and improved its thickness and density. Compared with the OVX group, the levels of tartrate-resistant acid phosphatase from 5b and C-terminal telopeptide of type I collagen were significantly reduced by 42.75% and 49.27% in the OVX + CE rats (p < 0.05). TRAP staining visually showed that the number of osteoclasts in the femur tissue of CE-treated rats was less than that of the OVX group. The expressions of nuclear factor of activated T-cells, cytoplasmic 1, acid phosphatase 5, and cathepsin K in OVX + CE rats were significantly decreased by 51.61%, 46.07%, and 50.34% compared to the OVX group (p < 0.01). In addition, CE intervention effectively reduced the phosphorylation levels of P65 and IκBα and inhibited the NF-κB signaling pathway. Meanwhile, CE diminished the number of multinucleated osteoclasts induced by receptor activator for nuclear factor-κB ligand and hindered cell fusion as well as nuclear translocation of osteoclast precursor cells P65. In conclusion, CE inhibits osteoclastogenesis by suppressing the activation of the NF-κB signaling pathway, thereby alleviating postmenopausal osteoporosis.

Bone marrow mesenchymal stem cells-derived exosomal lncRNA GAS5 mitigates heart failure by inhibiting UL3/Hippo pathway-mediated ferroptosis

BackgroundExosomes (Exos) are involved in the therapeutic effects of bone marrow mesenchymal stem cells (BMSCs) on heart failure (HF). We investigated the molecular mechanisms underlying the involvement of BMSC-Exos in ferroptosis on HF.MethodsA rat model of HF and cellular model of hypoxia were established. BMSC-Exos were injected into model rats or co-cultured with model cells. In model rats, the cardiac function (echocardiography), oxidative stress (commercial kits), pathological damage (HE staining), fibrosis (MASSON staining), iron deposition (Prussian blue staining), and cell apoptosis (TUNEL staining) were examined. Viability (cell counting kit-8; CCK-8), cell cycle (flow cytometry), oxidative stress, and Fe2+ levels were detected in the model cells. GAS5, UL3, YAP, and TAZ expression were detected using qRT-PCR, western blotting, and immunohistochemistry analyses.ResultsBMSC-Exos restored cardiac function and inhibited oxidative stress, apoptosis, pathological damage, fibrosis, and iron deposition in myocardial tissues of HF rats. In hypoxic cells, BMSC-Exos increased cell viability, decreased the number of G1 phase cells, decreased Fe2+ levels, and inhibited oxidative stress. Ferrostatin-1 (a ferroptosis inhibitor) exhibited a synergistic effect with BMSC-Exos. Additionally, GAS5 was upregulated in BMSC-Exos, further upregulating its target UL3 and Hippo pathway effectors (YAP and TAZ). The relieving effects of BMSC-Exos on HF or hypoxia-induced injury were enhanced by GAS5 overexpression, but weakened by UL3 silencing or verteporfin (a YAP inhibitor).ConclusionsGAS5-harbouring BMSC-Exos inhibited ferroptosis by regulating the UL3/Hippo pathway, contributing to HF remission in vivo and in vitro.