氯沙坦对在体实验性大鼠心肌缺血再灌注诱导的心肌细胞凋亡及基因表达影响的研究

A study on losartan′s influence on cardiomyocyte apoptosis induced by in vivo experimental rats′ischemia-reperfusion and their gene expression

目的 研究氯沙坦对大鼠在体心肌缺血再灌注后细胞凋亡的影响及bcl 2和bax基因表达。方法 采用末端标记、原位杂交、免疫组织化学 3种方法分别检测细胞凋亡、基因表达产物的mRNA和蛋白质 ,通过图像分析系统测量阳性染色区域的平均吸光度对原位杂交和免疫组织化学检测物质进行量化处理。结果 细胞凋亡数目手术对照组为 (38± 9)个 /HP ,假手术组为 (0～ 1 )个 /HP ,药物治疗组为 (9± 4)个 /HP ,各组间差异有非常显著性 (P <0 0 0 1 ) ;原位杂交bcl 2手术对照组为 0 0 75± 0 0 2 0 ,假手术组为 0 0 60± 0 0 1 0 ,治疗组为 0 0 76±0 0 1 4 ,免疫组织化学bcl 2手术对照组为 0 1 37± 0 0 1 4 ,假手术组为 0 0 85± 0 0 1 9,治疗组为 0 1 2 5± 0 0 2 1 ,对照组、治疗组的升高与假手术组之间差异有显著性 (P <0 0 5) ,治疗组和对照组之间差异无显著性 (P >0 1 ) ;免疫组织化学bax手术对照组为 0 0 97± 0 0 2 2、假手术组为 0 0 62± 0 0 1 4、治疗组为 0 0 62± 0 0 1 4 ,对照组的升高与治疗组、假手术组间差异有非常显著性 (P <0 0 0 1 ) ,治疗组和假手术组之间差异无显著性 (P >0 9) ;bcl 2 /bax比值手术对照组为 1 41 3 ,假手术组为 1 376 ,治疗组为 2 0 1 6。结论 氯?

Objective To study the changes of cardiomyocyte apoptosis and bcl 2 and bax gene expression after the rats of ischemia and reperfusion are treated by losartan.Methods The apoptotic cells are assessed by transferase mediated dUTP nick end labeling (TUNEL) staining means.The mRNA and protein of gene expression are measured by immunohistochemistry and in situ hybridization histochemistry (ISHH).In order to quantitatively process the positive tested substance in both immunohistochemistry and ISHH through the average absorbancy ( A ) value,image processing system is used.Results The number of the apoptotic cells is 38±9 (operative control group) and 0～1 (sham operating group) and 9±4 (therapeutic group) in each visual field respectively.Imparity between per two groups in three groups is all significant ( P <0 001). A value of bcl 2 (ISHH) is 0 075±0 020 (operative control group) and 0 060±0 010 (sham operating group) and 0 076±0 014 (therapeutic group) respectively, A value of bcl 2 (immunohistochemistry) is 0 137±0 014 (operative control group) and 0 085±0 019 (sham operating group) and 0 125±0 021 (therapeutic group), bcl 2 gene expression increases significantly in operative control group and therapeutic group compared with sham operating group ( P <0 05),there isn′t significantly variant between therapeutic group and operative control group ( P >0 1). A value of bax (immunohistochemistry) is 0 097±0 022 (operative control group) and 0 062±0 014 (sham operating group) and 0 062±0 014 (therapeutic group),bax gene expression decreases very significantly in therapeutic group and sham operating group compared with operative control group ( P <0 001),there isn′t significantly variant between therapeutic group and sham operating group ( P >0 9). Bcl 2/bax ratio is 1 413 (operative control group) and 1 376 (sham operating group) and 2 016 (therapeutic group).Conclusion Losartan may restrain cardiomyocyte apoptosis after ischemia and reperfusion.The action mechanism may be decreasing the bax gene expression resulting in increasing the bcl 2/bax ratio.