rhBNP通过抑制细胞凋亡减轻大鼠心肌缺血再灌注损伤

rh BNP Reduces Myocardial Ischemia-reperfusion Injury in Rats by Inhibiting Apoptosis

为了研究重组人B型钠尿肽(recombinant human B-type natriuretic peptide, rhBNP)对减轻大鼠心肌缺血再灌注损伤的机制,本研究采用尾部静脉注射的方法对I/R大鼠成功建模,并设计注射生理盐水(I/R组)、rhBNP (I/R+rhBNP组)和假手术组CK组3个处理组,通过TUNEL法检测各处理组大鼠心肌细胞的凋亡情况。本实验还用生理和生化方法检测了心肌细胞中超氧化物歧化酶(superoxidedismutase, SOD)和丙二醛(malondialdehyde, MDA)活性和含量的变化情况,用RT-PCR和免疫印迹方法检测了Bax/Bcl-2信号通路中基因和蛋白表达水平变化。结果表明,rhBNP可以提高I/R大鼠心肌细胞中SOD酶活性,同时使MDA含量降低,表明rhBNP能够保护心肌细胞,使细胞受损程度减小。与此同时本研究发现rhBNP处理后大鼠心肌细胞中Bax基因和蛋白的表达量显著下调,且Bcl-2基因和蛋白的表达显著上调,从而使I/R大鼠心肌细胞的凋亡数目减少,缩小心肌坏死的面积。本研究表明rhBNP可以通过调节Bax/Bcl-2信号通路、提高SOD酶活性使I/R大鼠心肌细胞内MDA含量减少,以及心肌细胞凋亡数目减少,从而有效地减轻大鼠心肌缺血再灌注损伤,以达到保护心肌细胞的目的。

To study the mechanism of recombinant human B-type natriuretic peptide(rhBNP) in alleviating myocardial ischemia-reperfusion injury in rats, I/R rats modeling were successfully by tail vein injection. Three treatment groups were designed: Injection of normal saline(I/R group), rhBNP(I/R+rhBNP group) and sham operation group CK group. The apoptosis of cardiomyocytes in each treatment group was detected by TUNEL method.The apoptosis of cardiomyocytes in the treated group was observed. The activity and content of superoxidedismutase(SOD) and malondialdehyde(MDA) in cardiomyocytes were also detected by physiological and biochemical methods. The expression levels of genes and proteins in Bax/Bcl-2 signaling pathway were detected by RT-PCR and Western blotting. The results of this experiment showed that rhBNP could increase SOD activity in I/R rat cardiomyocytes and decrease MDA content, indicating that rhBNP could protect cardiomyocytes and reduce cell damage. At the same time, the expression of Bax gene and protein was down-regulated in rat cardiomyocytes, and the expression of Bcl-2 gene and protein was up-regulated, which reduced the number of apoptosis of cardiomyocytes in I/R rats to protect cardiomyocytes. The results of this study indicated that rhBNP could effectively reduce the MDA content in cardiomyocytes of I/R rats and decrease the number of cardiomyocyte apoptosis by regulating Bax/Bcl-2 signaling pathway and increasing SOD activity. Effectively reduce myocardial ischemia-reperfusion injury in rats and achieve the purpose of protecting myocardial cells.