右美托咪定对缺血-再灌注损伤大鼠肾组织Bax/Bcl-2表达的影响

Effects of dexmedetomidine on expressions of Bax and Bcl-2 in renal tissues of rats with ischemia-reperfusion injury

目的探讨右美托咪定对缺血-再灌注(I-R)损伤大鼠肾组织Bax/Bcl-2表达的影响。方法 40只Wistar大鼠随机均分为五组:假手术组(S组),I-R组,右美托咪定组(D1、D2和D3组)。肾缺血45min、再灌注24h制备I-R损伤模型。D1、D2和D3组分别于缺血前30min腹腔注射右美托咪定25、50和75μg/kg,S组及I-R组给予等容量生理盐水。再灌注结束时取肾组织,观察组织病理学变化,TUNEL法测定细胞凋亡并计算凋亡指数(AI);免疫组化测定肾组织Bax和Bcl-2蛋白含量,计算Bax/Bcl-2比值。结果 S组肾组织形态学结构未见明显改变,I-R组的组织损伤程度较S组加重,D1、D2和D3组的损伤程度较I-R组减轻。与S组相比,I-R组、D1、D2和D3组的AI升高,Bax和Bcl-2蛋白表达均上调,Bax/Bcl-2比值增高(P<0.05)。与I-R组相比,D1、D2和D3组的AI下降,Bax表达下调,Bcl-2表达上调,Bax/Bcl-2比值降低(P<0.05)。结论右美托咪定可以减轻大鼠肾I-R损伤引起的细胞凋亡;其机制可能与调节Bax和Bcl-2的表达有关。

Objective To investigate the effects of dexmedetomidine on the expressions of Bax and Bcl-2 in renal tissues of rats with induced ischemia-reperfusion（I-R） injury. Methods Forty Wistar rats were equally randomized into five groups of S（sham operated）, I-R, D1, D2 and I）3. The models of rat renal I-R injury were produced by occlusion of both renal pedicles for 45 rain, which was followed by reperfusion for 24 hours. The rats in groups of D1, D2 and D3 were intraperitoneally injected with dexmedetomidine 25,50,and 75 btg/kg, respectively, at 30 rain before renal ischemia and those in groups of S and I-R were given equal volume of normal saline. The renal tissues were obtained for histopathological examination, apoptosis assay by TUNEL method and determination of the expressions of Bax and Bcl-2 proteins at the end of reperfusion. Results Renal tissues in group S had no significant histopathological changes. The degree of renal tissues injury was more serious in group I-R than that in group S, which was less in groups of D1, D2 and D3 than that in group I-tL Compared with group S, the apoptosis index, Bax and Bcl-2 expressions, and Bax/Bcl-1 ratio were increased in groups of I-R, D1, D2 and D3 （P〈0. 05）. Compared with group I-R, the apoptosis index, Bax expression and Bax/Bcl-2 ratio were decreased and Bcl-2 expression was increased in groups of D1 ,D2 and D3 （P〈0. 05）. Conclusion Dexmedetomidine can reduce cell apoptosis induced by renal I-R injury via adjusting the expressions of Bax and Bcl-2 in rats.