JAK/STAT信号通路在大鼠缺血再灌注心肌损伤中的表达

Expression of JAK/STAT Signal Pathway in Myocardial Injury of Ischemia Reperfusion in Rats

目的观察抑制Janus激酶-信号转导子与转录激活子(janus kinases-singnal transducers and activatorsof transcription,JAK/STAT)信号通路对大鼠心肌缺血再灌注(I/R)损伤的影响。方法选择健康Wistar大鼠24只,随机分为假手术组、I/R组、JAK抑制剂组、STAT抑制剂组,每组各6只。JAK抑制剂组、STAT抑制剂组于I/R前30 min腹腔内分别注射AG490(8 mg/kg)、西罗莫司(0.4 mg/kg)。I/R组、JAK抑制组、STATR抑制组以穿线法结扎左冠状动脉前降支制备心肌I/R大鼠模型,假手术组仅穿线不结扎。采用免疫印迹法检测大鼠心肌p-JAK2、p-STAT1及p-STAT3的表达情况。结果假手术组p-JAK2、p-STAT1、p-STAT3均有少量表达。与假手术组比较,I/R组p-JAK2、p-STAT1、p-STAT3和STAT抑制剂组p-JAK2、p-STAT1表达明显增加,差异均有统计学意义(P<0.01)。与I/R组比较,JAK抑制剂组p-JAK2、p-STAT1、p-STAT3表达均减少,STAT抑制剂组p-STAT3表达减少,差异均有统计学意义(P<0.05)。I/R组和STAT抑制剂组p-STAT1的表达均高于同组p-STAT3的表达,差异有统计学意义(P<0.05)。结论 JAK/STAT信号通路参与心肌I/R,应用AG490抑制JAK/STAT后信号通路激活可减轻心肌损伤,但STAT抑制剂在心肌I/R中的作用有待进一步探讨。

Objective To observe the effect on myocardial injury of ischemia reperfusion （I/R） in rats about restrai- ning signal pathway of janus kinases, singnal transducers and activators of transcription （ JAK-STAT）. Methods We choosed 24 healthy Wistar rats and divided them into sham operation group, I/R group, JAK inhibitor group and STAT inhibi- tor group. Each group had 6 rats. At 30 rain before I/R, JAK inhibitor group was injected with AG490 （8 mg/kg） while STAT inhibitor group was injected with Sirolimus （0.4 mg/kg）. At the rats＇ramus descendens anterior arteriae coronariae sin- istrae we used braid deligation to prepare the heart muscle in I/R group, JAK inhibitor group and STAT inhibitor group. We only used braid in sham operation group to explore the expression in examining the P-JAK2, P-STAT1, P-STAT3 of rats＇heart muscle in immunoblotting. Results The p-JAK2, P-STATI and p-STAT3 of sham operated group had small expression. The P-JAK2, P-STAT1 and P-STAT3 of I/R group and the P-JAK2, P-STAT1 of STAT inhibitor group were raised to compare with that of sham operated group, and the results had statistical significance（P 〈0.01 ）. The p-JAK2, p-STATI and p-STAT3 of JAK inhibitor group and the P-STAT3 of STAT inhibitor group were decreased to compare with that of I/R group, and the re- suits had statistical significance （ P 〈 0.05）. The p-STAT1 of I/R group and STAT inhibitor group were higher than that of p- STAT3 in expression of the same group, and the results had statistical significance （P 〈 0.05）. Conclusion The JAK/STAT signal pathway is involved in the myocardial injury of I/R. The JAK/STAT signal pathway is activated by using AG490 inhibi- ted JAK/STAT signal pathway, and myocardial damage can be reduced. The role STAT inhibitor in heart muscle I/R needs further research.