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目的探讨蛋白酶激活受体-2(PAR-2)活化对缺血再灌注(I/R)大鼠心肌细胞凋亡的影响及细胞外信号调节激酶(ERK)1/2在此过程中的作用。方法40只雄性SD大鼠随机均分为5组(n=8):假手术组,I/R组,PD组(0.3mg/kgERK1/2通路制剂PD98059),PAR-2AP组(3mg/kgPAR-2激活肽SLIGRL-NH2),PD+PAR-2AP组。建立大鼠在体心肌I/R模型。采用末端标记法(TUNEL)检测心肌细胞凋亡,免疫组织化学法检测各组凋亡相关蛋白Bcl-2、Bax的表达,Western blotting检测各组大鼠心肌组织中磷酸化ERK1/2(p-ERK1/2)的表达水平。结果与假手术组相比,I/R组、PD组、PAR-2AP组、PD+PAR-2AP组的凋亡指数,Bcl-2、Bax蛋白表达及p-ERK1/2水平均明显增高(P<0.01)。与I/R组比较,PAR-2AP可使凋亡指数和Bax蛋白表达降低,而使Bcl-2的表达和p-ERK1/2水平增加;与PAR-2AP组比较,PD+PAR-2AP组凋亡指数和Bax蛋白表达增加,Bcl-2的表达和p-ERK1/2水平降低。PAR-2AP抑制凋亡的效应可被PD98059部分阻断。结论PAR-2活化后可增加Bcl-2蛋白的表达,降低Bax的表达,从而部分抑制大鼠I/R心肌细胞的凋亡,发挥心肌保护效应,其机制可能涉及ERK路径。
Objective To investigate the effects of activation of PAR-2 on cardiomyocyte apoptosis in rats with ischemia / reperfusion (I / R) and the role of extracellular signal-regulated kinase (ERK) 1/2 in this process . Methods Forty male Sprague-Dawley rats were randomly divided into 5 groups (n = 8): sham operation group, I / R group, PD group (PD98059 0.3 mg / kg ERK1 / 2 pathway), PAR-2 AP group -2 activating peptide SLIGRL-NH2), PD + PAR-2AP group. Establishment of Rat Myocardial I / R Model in. The apoptosis of myocardial cells was detected by TUNEL, the expressions of Bcl-2 and Bax were detected by immunohistochemical method. The expressions of phosphorylated ERK1 / 2 (p- ERK1 / 2) expression levels. Results Compared with sham operation group, apoptosis index, Bcl-2, Bax protein expression and p-ERK1 / 2 level in I / R group, PD group, PAR-2AP group and PD + PAR-2AP group were significantly increased P <0.01). Compared with I / R group, PAR-2AP could decrease the expression of Bax and apoptosis index, and increase the expression of Bcl-2 and the level of p-ERK1 / 2. Compared with PAR-2AP group, PD + PAR-2AP group Apoptosis index and Bax protein expression increased, Bcl-2 expression and p-ERK1 / 2 levels decreased. The inhibitory effect of PAR-2AP on apoptosis can be partially blocked by PD98059. Conclusions Activation of PAR-2 may increase the expression of Bcl-2 protein and decrease the expression of Bax, thereby partially inhibiting the apoptosis of rat I / R cardiomyocytes and exerting the cardioprotective effect. The mechanism may involve the ERK pathway.