1.Role of JAK2-STAT3 pathway in reduction of myocardial ischemia-reperfusion injury by sufentanil postconditioning in dogs
Lixia NIE ; Shouyuan TIAN ; Yujie MENG ; Yan GAO ; Chensheng DUAN ; Baojiang LIU
Chinese Journal of Anesthesiology 2012;32(3):367-370
Objective To investigate the role of Janus kinese 2-signal transducer and activator of transcription 3 (JAK2-STAT3) pathway in reduction of myocardial ischemia-reperfusion (I/R) injury by sufentanil postconditioning in dogs.Methods Twenty-four healthy dogs of either sex,weighing 10-15 kg,were randomly divided into 4 groups (n =6 each):sham operation group (group S); I/R group; sufentanil postconditioning group (group PO) and sufentanil postconditioning + specific JAK2 inhibitor AG490 group (group AG).In groups I/R,PO and AG,myocardial I/R was produced by occlusion of left anterior descending coronary artery for 30 min followed by 120 min reperfusion.In groups PO and AG,sufentanil 0.6 μg/kg was infused intravenously over 5 min before reperfusion and in addition in group AG,AG490 1 mg/kg was injected intravenously before sufentanil infusion.Myocardial specimens were taken at the end of 120 min reperfusion for microscopic examination and determination of the expression of caspase-3 and p-STAT3 by immuno-histochemistry and myocardial cell apoptosis index (AI) by TUNEL.Results AI and the expression of caspase-3 and p-STAT3 were significantly higher in groups I/R,PO and AG than in group S ( P < 0.05).Compared with group I/R,AI and the expression of caspase-3 were significantly decreased in groups PO and AG,the expression of p-STAT3 was significantly increased in group PO,and the expression of p-STAT3 was significantly decreased in group AG ( P < 0.05).AI and the expression of caspase-3 were significantly higher and the expression of p-STAT3 was significantly lower in group AG than in group PO (P < 0.05).The pathologic changes were significantly attenuated in group PO compared with groups I/R and AG.Conclusion JAK2-STAT3 pathway is involved in reduction of myocardial I/R injury by sufentanil postconditioning in dogs.
2.Role of HMGB1-TLR4-mediated NF-κB signaling in adenosine pretreatment in protection against cerebral ischemia-reperfusion injury
Zhenxiang ZHANG ; Shouyuan GAO ; Yanwei LI ; He JI ; Jun TAN
Chinese Journal of Immunology 2024;40(3):491-496
Objective:To investigate the role of HMGB1-TLR4-NF-κB signaling pathway in cerebral ischemia-reperfusion in-jury and the effect of adenosine preconditioning on the signaling pathway.Methods:Total 80 adult male Sprague-Dawley rats weighing 220~270 g were selected from the Animal Center of Xinxiang Medical University.The rats were randomly divided into F group(sham operation group),I/R group(ischemia reperfusion group)and AP group(adenosine preconditioning group).The MCAO model of rats was established by wire embolization.Quantitative analysis of neural function in successfully modeled rats using animal behavior scor-ing method,the morphological changes of brain cells were observed by HE staining,TTC staining was used to observe cerebral infarc-tion and cerebral infarction volume was calculated;Immunohistochemical staining was used to detect HMGB1,TLR4 and NF-κB pro-tein expression levels in brain tissues of each group.The data were statistically analyzed by one-way ANOVA in SPSS26.0 software.Results:After ischemia reperfusion,the neurological function of I/R group and AP group showed different degrees of impairment,and the neurological function scores of the two groups were significantly higher than that of F group,the difference was statistically signifi-cant(P<0.05),and the neurological function of the AP group was significantly less than that of I/R group,the difference was also sta-tistically significant(P<0.05).TTC staining showed that AP group,I/R group rat cerebral infarction volume was significantly more than F group[(93.670±4.509)mm3,(123.670±7.234)mm3 vs(0.000±0.000)mm3],and AP group rats infarction volume was signifi-cantly reduced than that in I/R group,the difference had statistical significance(P<0.05).Immunohistochemistry showed that HMGB1,TLR4,NF-κB protein in F group with a small amount of expressions in rats,while significantly expressed in AP group and I/R group relatively,and the AP group of each subgroup rat HMGB1,TLR4,NF-κB protein expressions significantly lower than the amount of I/R group,the difference had statistical significance(P<0.05).Conclusion:Adenosine preconditioning can reduce the expressions of HMGB1,TLR4 and NF-κB protein,and then protect the rats with cerebral ischemia-reperfusion injury.