Protective Effects of Apigenin against Radiation-Induced Esophageal Injury: An Experimental Study in Rats

Effects of DMSO on a rabbit ear hypertrophic scar model: A controlled randomized experimental study

Influences of abaR gene on biofilm formation of Acinetobacter baumannii

Objective To investigate the effect and mechanism of necrostatin-1(Hec-1) on the level of HMGB-1 protein in liver of rats with hemorrhagic-traumatic shock. Methods A number of 96 male SD rats were divided into sham-operated group, dimethyl sulfoxide(DMSO) group and Nec-1 group (n=32 in each) by randomized number method. Rat model of hemorrhagic-traumatic shock was made by fracture of femoral bone and tibia bone and exsanguination from femoral vein until 30 mmHg and maintained at 30-40 mmHg for 90 min, then the shed blood was transfused back with Ringer's solution. The rats in sham-operated group were only under anesthesia for separating and ligating blood vessels, without exsanguination to induce hemorrhagic shock and without replenishment with blood. Rats in Nec-1 group were given 1 mg/kg Nec-1 through femoral vein 5 min before replenishment with blood and Ringer's solution, while the rats in DMSO group were given equal volume of DMSO solution instead. Eight rats in each group were sacrificed separately at 2 h, 8 h, 16 h and 24 h after replenishment. The serum and liver tissues of rats in each group were collected to detect serum alanine aminotransferase(ALT) and aspartate aminotransferase(AST), and to observe the pathological changes in liver with hematoxylin-eosin(HE) staining. The level of HMGB-1 in serum was detected by using ELISA. The cytoplasm protein and total protein expressions of HMGB-1 were assessed by using western blot analysis. Results Compared with DMSO group, levels of serum ALT at 8 h(P<0.05), 16 h(P<0.01) and 24 h(P<0.01) in Nec-1 group were significantly lower. Level of serum AST in Nec-1 group were lower compared with DMSO group at 8 h(P<0.01), 16 h(P<0.01) and 24 h(P<0.01). Compared with DMSO group, levels of serum HMGB-1 at 8 h(P<0.05), 16 h(P<0.01) and 24 h(P<0.01) in Nec-1 group were significantly lower. Under light microscopy and transmission electron microscope, hepatic lobule destroyed, the blood extravasated, the immunocyte infiltrated and cellular organelle destroyed were found. Compared with DMSO group, the level of HMGB-1 protein in cytoplasm protein in Nec-1 group were significantly decreased at 8 h(P<0.01), 16 h(P<0.01) and 24 h(P<0.01). The level of HMGB-1 protein in total protein in Nec-1 group were significantly decreased 8 h(P<0.05) and 24 h(P<0.05). Conclusions Nec-1 can remarkably protect the liver of rats with hemorrhagic-traumatic shock, decrease the level of HMGB-1, and protect the hepatocyte effectively. Key words: High mobility group protein B1; Trauma; Shock, Hemorrhagic; Necrostatin-1; Necroptosis

To evaluate the effect of sorafenib in murine high risk keratoplasty model. Graft survival, corneal neovascularization, and corneal lymphangiogenesis were compared among the sorafenib, dexamethasone, dimethyl sulfoxide (DMSO), and phosphate buffered saline (PBS) groups following subconjunctival injection in mice that underwent high risk penetrating keratoplasty (HRPK). Real-time polymerase chain reaction was performed to quantify the expression of inflammatory cytokines and vascular endothelial growth factor (VEGF)-A, VEGF-C, vascular endothelial growth factor receptor (VEGFR)-2, VEGFR-3. The two-month graft survival rate for HRPK was 42.86% in sorafenib group, 37.50% in dexamethasone group, 0 in DMSO group, and 0 in PBS group. Sorafenib significantly increased graft survival compared to the DMSO and PBS group (P<0.05). The sorafenib didn't show significant effect in decreasing neovascularization compared with dexamethsone, DMSO, and PBS group. The sorafenib showed less total lymphangiogenesis than the dexamethasone, DMSO, and PBS group (P=0.011, P<0.001, P<0.001, respectively). The sorafenib group showed reduced expression of VEGF-C, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, VEGFR-2 and VEGFR-3 compared with DMSO group and PBS group (all P<0.05). The sorafenib group didn't show difference in the expression of VEGF-A compared with DMSO, neither with PBS. The sorafenib group showed reduced expression of VEGFR-3 compared with dexamethasone (P=0.051). The subconjunctivally administered sorafenib shows significant anti-lymphangiogenic effect, resulting in increased transplant survival in a murine high risk keratoplasty model. We suggest that a close linkage between decreased VEGF-C/VEGFR-2 and -3 signaling and increased corneal graft survival by sorafenib seems to exist.

Objective To investigate the antioxidative effects of all-trans retinoic acid (ATRA) on the intestinal ischemia reperfusion.Methods Thirty-two male SD rats were randomly divided into the sham operation group,occlusion group,dimethyl sulfoxide (DMSO) group and the ATRA group according to the random number table.There were 8 rats in each group.Rat models of intestinal ischemia reperfusion were established by clamping the superior mesenteric arteries for 60 minutes,and then restore the blood flow for 120 minutes.Superior mesenteric arteries were only separated without clamping in the sham operation group.Rats in the ATRA group received ATRA pretreatment through intragastric infusion at the dosage of 15 μg/g for 5 days,and then ATRA pretreatment at 6 hours before operation.Rats in the DMSO group received intragastric infusion of DMSO at the same dosage.The concentration of ATRA at 5 hours before operation was detected by high performance liquid chromatography.The pathomorphological changes of the ileal mucosa were detected by hematoxylin-eosin staining,and the Chiu's scores on the ileal mucosa were evaluated.The serum content of diamine oxidase (DAO),tissue level of malonaldehyde (MDA) and activity of superoxide dismutase (SOD) were detected by colorimetry.Protein expression of manganese superoxide dismutase (MnSOD) in the ileal tissues was detected by Western blot.All data were analyzed using the analysis of variance or LSD-t test.Results The concentrations of ATRA in the ATRA group was (827 ±276) μg/L,which was significantly higher than (48 ± 12) μg/L of the sham operation group,(55 ± 15) μg/L of the occlusion group and (63 ± 20) μg/L of the DMSO group (t =11.242,11.138,11.013,P ＜ 0.05).The morphology of the ileal mucosa was normal in the sham operation group,while the ileal mucosa was severely damaged in the occlusion group and the DMSO group.The injury of the ileal mucosa in the ATRA group was slight.The Chiu's scores of the occlusion group,DMSO group and the ATRA group were 3.83 ±0.77,3.92 ± 0.87 and 2.42 ± 0.75,which were significantly higher than 0.37 ± 0.28 of the sham operation group (t =9.803,10.040,5.793,P ＜0.05).The Chiu's scores of the ATRA group was significantly lower than that of the occlusion group and the DMSO group (t =4.009,4.247,P ＜ 0.05).The DAO levels of the occlusion group,DMSO group and the ATRA group were (26.3 ±4.4)U/L,(25.1 ± 4.3)U/L and (20.8 ±3.8)U/L,which were significantly higher than (14.2 ± 1.9) U/L of the sham operation group (t =6.493,5.835,3.534,P ＜ 0.05).The level of DAO of the ATRA group was significantly lower than that of the occlusion group and the DMSO group (t =2.959,2.301,P ＜0.05).The levels of MDA of the occlusion group,DMSO group and the ATRA group were (16.9 ± 4.0) μmol/g,(16.0 ± 3.5) μmol/g and (11.3 ± 3.1) μmol/g,which were significantly higher than (5.4 ± 1.0) μmol/g of the sham operation group (t =7.397,6.821,3.821,P ＜ 0.05).The level of MDA of the ATRA group was signifcantly lower than that of the occlusion group and the DMSO group (t =3.575,3.000,P ＜ 0.05).The SOD activity of the occlusion group,DMSO group and the ATRA group were (108 ±22) U/mg,(98 ± 19) U/mg and (181 ± 38)U/mg,which were significantly lower than (243 ± 37)U/mg of the sham operation group (t =8.939,9.647,4.106,P ＜ 0.05).The SOD activity of the ATRA group was significantly higher than that of the occlusion group and the DMSO group (t =4.833,5.541,P ＜ 0.05).The relative protein expressions of the MnSOD of the occlusion group and the DMSO group were 0.36 ± 0.08 and 0.28 ± 0.07,which were significantly lower than 0.93 ± 0.13 of the sham operation group (t =8.972,10.101,P ＜ 0.05).The relative protein expression of the MnSOD of the ATRA group was 0.80 ± 0.19,which was significantly higher than that of the occlusion group and the DMSO group (t =6.948,8.077,P ＜ 0.05),while it was not significantly different from that of the sham operation group (t =2.024,P ＞ 0.05).Conclusion Through up-regulating the expression of MnSOD and improving the antioxidative capacity of tissue,ATRA pretreatment can attenuate intestinal ischemia and reperfusion injury. Key words: Ischemia reperfusion injury, intestinal; Antioxidants; All-trans retinoic acid

Objectives — Pretreatment with diazoxide, a mitochondrial ATP-sensitive potassium channel (mito KATP) opener, was found to protect the rat heart against ischaemia-reperfusion (I/R) injury by mimicking ischaemic preconditioning (IPC). However, the protection mechanisms have not been fully clarified yet. We hypothesize that molecular regulation of mitochondrial energetics is integral to this cardioprotective programme. We explored the involvement of peroxisome proliferator-activated receptor g coactivator-1-1α (PGC-1α) in the effect of IPC and diazoxide preconditioning (DPC) with regard to its role in protection against I/R injury.Methods — 30 Wistar rats were used to establish the Langendorff isolated perfused heart model. Rats were randomly divided into 5 groups, 6 in each group: (1) the I/R group: after 30 min of equilibration perfusion, the heart was subjected to 30 min of ischaemia and 1h of reperfusion; (2) the IPC group: after 10 min of equilibration perfusion, the heart was subjected to two times 5 min ischaemia and 5 min of reperfusion, followed by 30 min of ischaemia and 1h of reperfusion; (3) the DPC group: after 10 min of equilibration perfusion, the heart was given two times a K-H perfusion solution containing diazoxide (100 mmol/l) for 5 min then a non-diazoxide K-H perfusion solution for 5 min, followed by 30 min of ischaemia and 1h of reperfusion; (4) a blank control group: an equal amount of saline was used instead of diazoxide. The perfusion procedure was the same as in the DPC group; (5) the dimethyl sulfoxide (DMSO) group: DMSO was applied instead of diazoxide, and the perfusion procedure was the same as in the DPC group. Cardiac apex muscle was cut for frozen section. Immunohistochemistry staining of PGC-1α was performed and average absorbance was calculated. An electron microscope was used for Flameng scoring of the myocardial mitochondria.Results — The average absorbance values of PGC-1α were: I/R group (3.88 ± 1.72), IPC group (10.94 ± 5.23), DPC group (8.40 ± 3.64), blank control group (3.55 ± 1.56) and DMSO group (4.16 ± 0.52), respectively. The expression of PGC-1α was significantly increased in the IPC and DPC groups and the differences were statistically significant compared to the I/R, blank control and DMSO groups, i.e., P < 0.01 for IPC group and P < 0.05 for DPC group. However, there was no significant difference between the IPC and DPC groups (P > 0.05). Flameng score: IPC group (0.44 ± 0.13), DPC group (0.47 ± 0.10), I/R group (1.78 ± 0.14), blank control group (1.70 ± 0.03) and DMSO group (1.68 ± 0.06). The Flameng score of the IPC and DPC groups was statistically significantly different as compared to the I/R group, blank control group and DMSO group (P < 0.01), but no significant difference was detected between the IPC and DPC groups (P > 0.05).Conclusion — IPC and DPC have a protective effect on myocardial mitochondria, and their mechanism of action may be related to activation and over-expression of PGC-1α.

miRNAs appear to play an important role in controlling the expression of several genes, and they are a potential biomarker and prognostic tool in gastric diseases. We analyzed 53 controls, 86 patients with gastritis, and 19 patients with gastric cancer. Real-time-PCR was used to determine the expression levels of miRNA-146a, miRNA-155, IL-2, and TNF-α. The subsequent analysis of the target genes was performed using the bioinformatics approach. There was no difference in IL-2 expression between the groups. However, there was a significant increase in TNF-α expression in the gastritis group relative to the control and a significant decrease in the gastric cancer group relative to the control. There was also a statistically significant increase in miRNA-146a and miRNA-155 expression in the gastritis group relative to the control, but not in the gastric cancer group. Similar results were found when the presence of H. pylori was considered. The data revealed an increase in miRNA-146a and miRNA-155 expression but not enough to control the expression of TNF-α. The presence of H. pylori was found to affect increases in TNF-α and microRNA expression, and miRNA-146a and miRNA-155 alone were not able to eliminate bacteria or restore tissue homeostasis.

Objective: To explore the expression pattern of aryl hydrocarbon receptor (AhR) in mice peritoneal macrophages (PMs) after major trauma and analyze the effects of enhanced AhR expression on the inflammatory cytokine level and bactericidal ability after trauma. Methods: The experimental study method was used. Forty 6-8-week-old male C57BL/6J mice (the same mouse age, sex, and strain below) were divided into control group, post trauma hour (PTH) 2 group, PTH 6 group, and PTH 12 group according to the random number table (the same grouping method below), with 10 mice in each group. Mice in the latter 3 groups were constructed as severe trauma model with fracture+blood loss, while mice in control group were left untreated. The primary PMs (the same cells below) were extracted from the mice in control group, PTH 2 group, PTH 6 group, and PTH 12 group when uninjured or at PTH 2, 6, and 12, respectively. Then the protein and mRNA expressions of AhR were detected by Western blotting and real-time fluorescence quantitative reverse transcription polymerase chain reaction, respectively, and the gene expressions of AhR signaling pathway related molecules were analyzed by transcriptome sequencing. Twenty mice were divided into control group and PTH 6 group, with 10 mice in each group, and the PMs were extracted. The level of ubiquitin of AhR was detected by immunoprecipitation. Twelve mice were divided into dimethyl sulfoxide (DMSO) alone group, PTH 6+DMSO group, MG-132 alone group, and PTH 6+MG-132 group, with 3 mice in each group. After the corresponding treatment, PMs were extracted, and the protein expression of AhR was detected by Western blotting. Twenty mice were constructed as PTH 6 model. Then, the PMs were extracted and divided into empty negative control adenovirus (Ad-NC) group and AhR overexpression adenovirus (Ad-AhR) group. The protein expression of AhR was detected by Western blotting at 36 h after some PMs were transfected with the corresponding adenovirus. The rest cells in Ad-NC group were divided into Ad-NC alone group and Ad-NC+endotoxin/lipopolysaccharide (LPS) group, and the rest cells in Ad-AhR group were divided into Ad-AhR alone group and Ad-AhR+LPS group. The expressions of interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) in the cell supernatant were detected by enzyme-linked immunosorbent assay at 12 h after the corresponding treatment (n=6). Twenty mice were obtained to extract PMs. The cells were divided into control+Ad-NC group, PTH 6+Ad-NC group, control+Ad-AhR group, and PTH 6+Ad-AhR group, and the intracellular bacterial load was detected by plate spread method after the corresponding treatment (n=6). Data were statistically analyzed with one-way analysis of variance, least significant difference test, analysis of variance for factorial design, and independent sample t test. Results: Compared with 1.16±0.28 of control group, the protein expressions of AhR in PMs in PTH 2 group (0.59±0.14), PTH 6 group (0.72±0.16), and PTH 12 group (0.71±0.17) were all significantly decreased (P<0.05). The overall comparison of the difference of AhR mRNA expression in PMs among control group, PTH 2 group, PTH 6 group, and PTH 12 group showed no statistical significance (P>0.05). The AhR signaling pathway related molecules included AhR, AhR inhibitor, cytochrome P450 family member 1b1, cytochrome P450 family member 11a1, heat shock protein 90, aryl hydrocarbon receptor-interaction protein, and heat shock protein 70 interaction protein. The heat shock protein 90 expression of PMs in PTH 2 group was higher than that in control group, while the expressions of other molecules did not change significantly after trauma. Compared with that in control group, the level of ubiquitin of AhR in PMs in PTH 6 group was increased. Compared with that in DMSO alone group, the protein expression of AhR in PMs in PTH 6+DMSO group was decreased, while that in PMs in MG-132 alone group had no significant change. Compared with that in PTH 6+DMSO group, the protein expression of AhR in PMs in PTH 6+MG-132 group was up-regulated. At transfection hour 36, compared with that in Ad-NC group, the protein expression of AhR in PMs in Ad-AhR group was increased. At treatment hour 12, compared with those in Ad-NC+LPS group, the expressions of IL-6 and TNF-α in PM supernatant of Ad-AhR+LPS group were significantly decreased (with t values of 4.80 and 3.82, respectively, P<0.05). The number of intracellular bacteria of 1×106 PMs in control+Ad-NC group, PTH 6+Ad-NC group, control+Ad-AhR group, and PTH 6+Ad-AhR group was (3.0±1.8), (41.8±10.2), (1.8±1.2), and (24.2±6.3) colony forming unit, respectively. Compared with that in PTH 6+Ad-NC group, the number of intracellular bacteria of PMs in PTH 6+Ad-AhR group was significantly decreased (t=3.61, P<0.05). Conclusions: Ubiquitin degradation of AhR in PMs of mice after major trauma results in decreased protein expression of AhR. Increasing the expression of AhR in post-traumatic macrophages can reduce the expressions of LPS-induced inflammatory cytokines IL-6 and TNF-α, and improve the bactericidal ability of macrophages after trauma.

This study aimed to determine the effect of Alpha Lipoic Acid (ALA) supplementation on in vitro maturation media of goat oocytes on Tumor Necrosis Factor Alpha (TNF-α) expression and Malondialdehyde (MDA) levels. This laboratory experimental study consisted of three treatment groups: control group (G0), 25 μmol/L ALA supplementation (G1), and 50 μmol/L ALA supplementation (G2). A total of 366 goats Cumulus Oocyte Complex (COCs) were collected, then selected into 216 COCs, and matured in vitro for 22 hours in a 5% CO2 incubator, 98% humidity, 38.50C temperature. After that, TNF-α expression was identified using Immunocytochemistry staining with the addition of TNF-α antibody and calculated using the Remmele Scale Index. Measurement of MDA levels using the ELISA method. The data obtained were analyzed using Kruskal-Wallis, One Way ANOVA, and Duncan’s in the SPSS 24 software program (p&lt;0.05). The expression value of TNF-α G0 was 0.75±1.39, G1 was 5.56±3.05, and G2 was 2.00±1.80. MDA levels of G0 were 26.52 ±2.92, G1 was 46.44 ±4.87, and G2 was 30.41±5.67. TNF-α expression data and MDA levels G0 and G2 didn’t show a significant difference, while G0 and G2 compared to G1 showed a significant difference (p&lt;0.05). ALA supplementation of 25 µmol/L increased TNF-α expression or MDA levels and 50 µmol/L on in vitro maturation media of goat oocytes could reduce TNF-α expression or MDA levels than 25 µmol/L.

Objective To investigate the effect of Genistein, a tyrosinase inhibitor, on retinal neovascularization in mice. Methods Thirty-six 7-day-old C57BL/6J mice were randomly assigned into hyperoxia-induced group, Genistein group, DMSO group and normal control group.The mice in the hyperoxia-induced group, Genistein group and DMSO group were fed in a static chamber with the oxygen volume fraction (75±2)% for 5 days and then sent back to natural environment for 5 days to establish retinal neovascular models, and 1 μl Genistein diluted by 5% dimethyl sulfoxide (DMSO) (400 mg/L) and 1 μl DMSO were intravitreally injected in the 12-day-old mice of Genistein group and DMSO group, respectively.The mice in the normal control group were bred in natural environment.The fluorescence angiography was carried out in 17-day-old mice (2 mice in each group) to prepare the whole retinal flatmounts, and the morphology of retinal vessels was observed under the fluorescence microscope.The other mice in various groups were sacrificed and the retinas were collected.The expressions of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in mRNA and protein levels were detected by real-time fluorescence quantitative PCR and Western blot, respectively.The use and care of the mice complied with regulations for the management of laboratory animals. Results Retinal vessels were normal in the mice of normal control group.In the mice of the hyperoxia-induced group and DMSO group, retinal vessels were tortuous, and neovacularization and non-perfusion areas were visible.In the Genistein group, retinal vessels were clearly visible, but non-perfusion areas were exhibited.The relative expression levels of VEGF mRNA in retinas were 0.64±0.25, 0.37±0.23, 0.03±0.02 and 0.04±0.02, and the relative expression levels of bFGF mRNA in retinas were 21.40±3.07, 17.22±2.63, 0.52±0.25 and 0.67±0.23, in the hyperoxia-induced group, DMSO group, Genistein group and normal control group, and the expressions of VEGF and bFGF in mRNA level in the hyperoxia-induced group and DMSO group were significantly higher than those in the Genistein group and normal control group (all at P<0.05). The protein expression levels of VEGF and bFGF were 1.01±0.05 and 0.97±0.06 in the hyperoxia-induced group, 1.06±0.07 and 1.03±0.08 in the DMSO group, 0.73±0.05 and 0.76±0.07 in the Genistein group, 0.52±0.05 and 0.56±0.05 in the normal control group.The expressions of VEGF and bFGF in protein level in the hyperoxia-induced group and DMSO group were significantly higher than those in the Genistein group and normal control group (all at P<0.05). Conclusions Genistein can inhibit hyperoxia-induced retinal neovascularization may be by down-regulating the expressions of VEGF and bFGF in retinas. Key words: Angiogenesis inhibitors/pharmacology; Neovascularization, retinal; hyperoxia; Vascular endothelial growth factor; Fibroblast growth factor

Effects of P311 on the angiogenesis ability of human microvascular endothelial cell 1 in vitro and its molecular mechanism

We used the local lymph node assay to evaluate the abilities of chromated copper arsenate (CCA), a commonly used wood preservative, and its components to cause sensitizing reactions after their dilution in acetone-olive oil (AOO) and dimethyl sulfoxide (DMSO). After CBA/J mice were treated topically with 0.3 to 10% CCA, 0.3–3% chromium oxide, 0.3–3% arsenic oxide, or 0.3–3% copper oxide, their auricular lymph nodes (LN) were weighed and used in lymphocyte proliferation assays. In addition, total levels of chromium and arsenic in blood samples were measured. In all groups treated with CCA in AOO or DMSO, all parameters, including LN weight and lymphocyte proliferation, increased in a dose-dependent manner. The stimulation index (SI; the mean [3H]-TdR incorporation of the treatment group divided by that of the control group) showed a positive response (SI > 3) in all treatment groups; the EC3 values (estimated concentration to yield SI of 3) of CCA in AOO and DMSO were 1.86% and < 0.3%, respectively. In addition, we confirmed that the three components of CCA - chromium oxide, arsenic oxide and copper oxide—each individually exerted sensitizing ability. Mice treated with arsenic oxide in AOO or DMSO yielded nearly equal positive responses; however, the LLNA responses in mice treated with chromium oxide and copper oxide was much higher in the DMSO groups than in the AOO groups. The total chromium level in blood was higher in DMSO groups than AOO groups, whereas arsenic levels were comparable between the DMSO and AOO groups. Our findings suggest that CCA has sensitizing activity and that the type of solvent used can influence the results of sensitization assays evaluating metals.

AIMTo investigate the effects of herb-partitioned moxibustion (HPM) on phosphorylation of mitogen-activated extracellular signal-regulated kinase (MEK)1, extracellular signal-regulated kinase (ERK)1/2 and cAMP response element binding protein (CREB) in spinal cord of rats with chronic inflammatory visceral pain (CIVP), and to explore the central mechanism of HPM in treating CIVP.METHODSMale Sprague-Dawley rats were randomized into normal, model, HPM, sham-HPM, MEK-inhibitor and dimethyl sulfoxide (DMSO) groups. The CIVP model was established using an enema mixture of trinitrobenzene sulfonic acid and ethanol. HPM was applied at bilateral Tianshu (ST25) and Qihai (CV6) acupoints in the HPM group, while in the sham-HPM group, moxa cones and herb cakes were only placed on the same points but not ignited. The MEK-inhibitor and DMSO groups received L5-L6 intrathecal injection of U0126 and 30% DMSO, respectively. Abdominal withdrawal reflex (AWR), mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were applied for the assessment of pain behavior. The colonic tissue was observed under an optical microscope after hematoxylin-eosin staining. Expression of phosphor (p)MEK1, pERK1/2 and pCREB in rat spinal cord was detected using Western blotting. The levels of MEK, ERK and CREB mRNA in rat spinal cord were detected using real-time polymerase chain reaction.RESULTSCompared with the normal group, the AWR scores were increased significantly (P < 0.01) and the MWT and TWL scores were decreased significantly (P < 0.05) in the model, sham-HPM and DMSO groups. Compared with the model group, the AWR scores were decreased significantly (P < 0.01) and the MWT and TWL scores were increased significantly in the HPM and MEK-inhibitor groups (P < 0.05). Compared with the sham-HPM and DMSO groups, the AWR scores were decreased significantly (P < 0.01) and the MWT and TWL scores were increased significantly (P < 0.05) in the HPM and MEK-inhibitor groups. Compared with the normal group, the expression of pMEK1, pERK1/2 and pCREB proteins and the levels of MEK, ERK and CREB mRNA in rat spinal cord were increased significantly in the model, sham-HPM and DMSO groups (P < 0.01 or < 0.05). Compared with the model group, the expression of pMEK1, pERK1/2 and pCREB proteins and the levels of MEK, ERK and CREB mRNA in rat spinal cord were reduced significantly in the HPM and MEK-inhibitor groups (P < 0.01 or < 0.05). Compared with the sham-HPM and DMSO groups, expression of pMEK1, pERK1/2 and pCREB proteins and the levels of MEK, ERK and CREB mRNA in rat spinal cord were reduced significantly in the HPM and MEK-inhibitor groups (P < 0.01 or < 0.05).CONCLUSIONHPM down-regulates protein phosphorylation of MEK1, ERK1/2 and CREB, and mRNA expression of MEK, ERK and CREB, inhibiting activation of the MEK/ERK/CREB signaling pathway in the spinal cord of CIVP rats, which is possibly a critical central mechanism of the analgesic effect of HPM.

ObjectiveIschemic preconditioning (IPC) is an important endogenous protective mechanism for ischaemia-reperfusion (I/R) injury. Currently, it is believed that opening of the mitochondrial ATP-sensitive potassium channel (mitoKATP channel) plays an important...

Effects and molecular mechanism of exogenous L-carnitine on excessive endoplasmic reticulum stress-mediated hepatic pyroptosis in severely scald rats