新疆医科大学学报

目的 探讨α_2AR/PI3K/Akt通路在大鼠肾缺血再灌注后心肌细胞凋亡中的作用以及右美托咪定器官保护作用的机制。方法 选取40只雄性、10周龄，体重250～300 g, Wistar大鼠按随机数字表法分为5组：假手术组(Sham组)、缺血再灌注组(I/R组)、右美托咪定组(Dex组)、右美托咪定+I/R组(Dex+I/R组)、阿替哌唑+右美托咪定+I/R组(Atip+Dex+I/R组),各8只，分别按相应处理方式。对大鼠采取肾缺血45 min再灌注4 h处理，留取心肌组织，采用HE染色、TUNEL染色观察各组大鼠心肌组织损伤及凋亡情况；Western Blot法检测PI3K、Akt、p-Akt、Bcl-2、Bax蛋白表达分析α_2AR/PI3K/Akt通路在心肌凋亡中的作用。结果 与Sham组比较，右美托咪定预处理组大鼠心肌纤维排列较整齐，心肌纤维间散在部分慢性炎细胞浸润；部分心肌细胞可见空泡变性；可观察到小部分心肌纤维溶解坏死；心肌的凋亡率明显降低。与Sham组比较，Akt蛋白表达水平在各组差异无统计学意义(P>0.05);I/R组PI3K、p-Akt、Bcl-2蛋白表达水平均呈现明显降低(P<0.05),Bax蛋白明显升高(P<0.05);与I/R组比较，Dex+I/R组PI3K、p-Akt、Bcl-2水平均显著上升(P<0.05),Bax水平显著降低(P<0.05);与Dex+I/R组比较，Atip+Dex+I/R组PI3K、p-Akt蛋白表达水平均呈现明显降低(P<0.05),Bax蛋白表达水平呈现明显增加(P<0.05)。结论 右美托咪定可能通过α₂肾上腺素受体激活PI3K而使其下游的直接靶点Akt磷酸化，抑制心肌细胞凋亡，对肾缺血再灌注后心肌细胞凋亡起到保护作用。

Objective To investigate the role of α_2AR/PI3K/Akt pathway in cardiomyocyte apoptosis after renal ischemia-reperfusion in rats and the mechanism of organ protection of dexmedetomidine.Methods 40 male Wistar rats,aged 10 weeks,weighing 250～300g,were selected and fed in strict accordance with the requirements of theclean grade rats.Randomized numerical table method was used to divide the rats into 5 groups:sham operation group(Sham group),ischemia reperfusion group (I/R group),dexmedetomidine group (Dex group),dexmedetomidine+I/R group (Dex+I/R group),and atepiprazole+dexmedetomidine+I/R group (Atip+Dex+I/R group),8 rats in each group.The rats were treated with renal ischemia for 45 min and reperfusion for 4 hours,and the myocardial tissue was taken.HE staining and TUNEL staining were used to observe the myocardial tissue damage and apoptosis of the rats in each group;The Western Blot Assay were used to check PI3K,Akt,p-Akt,Bcl-2 and Bax protein expression and analysis the role of α_2AR/PI3K/Akt pathway in myocardial apoptosis.Results Compared with Sham group,the myocardial fibers of rats pretreated with dexmedetomidine were arranged orderly,and the chronic inflammatory cells infiltrated between myocardial fibers;the myocardial cells showed vacuolar degeneration;dissolution and necrosis of a small part of myocardial fibers were observed.The apoptosis rate of myocardium was significantly decreased.Compared with Sham group,there was no significant difference in Akt protein expression among the groups(P>0.05);In I/R group,the expression levels of PI3K,p-Akt and Bcl-2 protein were significantly decreased (P<0.05),while Bax protein was significantly increased (P<0.05);Compared with I/R group,the levels of PI3K,pAkt and Bcl-2 in Dex+I/R group were increased significantly (P<0.05),while the levels of Bax were decreased significantly (P<0.05);Compared with Dex+I/R group,the expression level of PI3K and p-Akt protein in Atip+Dex+I/R group were decreased significantly (P<0.05),while the expression level of Bax protein was increased significantly (P<0.05);The rest had no significant difference (P>0.05).Conclusion Dextrmedetomidine may pass α_2adrenaline receptor activates PI3K and phosphorylates its downstream direct target Akt,which inhibits cardiomyocyte apoptosis and protects cardiomyocyte apoptosis after renal ischemia/reperfusion.