吡那地尔对大鼠局灶性脑缺血再灌注后caspase-3及Bcl-2蛋白表达的影响

Effects of pinacidil on expression of caspase-3 and Bcl-2 proteins following cerebral ischemia-reperfusion in rats

目的探讨吡那地尔对大鼠局灶性脑缺血再灌注后Caspase-3及Bcl-2蛋白表达的影响。方法40只Wistar雄性大鼠随机分为假手术组、对照组、KATP开放剂治疗组(开放剂组)及KATP开放剂+阻断剂治疗组(阻断剂组)。应用线栓法制备大鼠大脑中动脉缺血模型(MCAO),应用TTC染色检测脑梗死体积,应用TUNEL法检测神经元凋亡,应用免疫组化方法检测caspase-3及Bcl-2蛋白表达。结果开放剂组脑梗死体积显著小于对照组和阻断剂组(P<0.01),对照组与阻断剂组之间差异无显著性(P>0.05);开放剂组神经元凋亡数较对照组和阻断剂组显著减少(P<0.01)。对照组与阻断剂组之间差异无显著性(P>0.05);开放剂组caspase-3蛋白表达显著少于对照组和阻断剂组(P<0.01),对照组与阻断剂组之间差异无显著性(P>0.05);开放剂组Bcl-2蛋白表达显著多于对照组和阻断剂组(P<0.01),对照组与阻断剂组之间差异无显著性(P>0.05)。结论KATP通道开放剂能显著减轻脑缺血再灌注后脑梗死体积、减少Caspase-3蛋白表达、增加Bcl-2蛋白表达、抑制神经元凋亡,对脑缺血再灌注损伤发挥保护作用。

[Objective] To study the effect of pinacidil on the expression of Caspase-3 and Bcl-2 proteins following focal cerebral ischemia-reperfusion. [Methods] 40 male Wistar rats were randomly divided into sham-operated group, control group, KATP opener treatment group （KATP opener group） and KATP opener and blocker treatment group（KATP blocker group）. The middle cerebral artery occlusion （MCAO） models were established by using the intraluminal suture occlusion method, the infarct volumes were studied by TTC staining, neuronal apoptosis was detected by TUNEL staining, the expression of caspase-3 and Bcl-2 proteins was detected by immunohistochemical staining. [Results] The infarct volumes of KATP opener group were significandy less than those of control group and KATP blocker group （P 〈0.01）. There were no differences between control group and KATP blocker group （P 〉0.05）; The number of apoptotic neurons in KATP opener group was significandy less than that in control group and KATP blocker group （P 〈0.01）, there were no differences between control group and KATP blocker group （P 〉0.05）. The expression of caspase-3 protein in KATP opener group was significandy less than that in control group and KATP blocker group （P 〈 0.01）, there were no differences between control group and KATP blocker group （P 〉0.05）. The expression of Bcl-2 protein in KATP opener group was significantly higher than that in control group and KATP blocker group （P 〈0.01）, there were no differences between control group and KATP blocker group （P 〉0.05）. [Conclusion] KATP opener has a protective effect on cerebral ischemia-reperfusion by significantly decreasing the infarct volumes, increasing the expression of Bcl-2 protein, decreasing the expression of caspase-3 protein and neuronal apoptosis.