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目的探讨磷酸肌酸钠及丹参酮ⅡA磺酸钠对阿霉素心肌病大鼠心肌细胞内质网应激凋亡作用。方法 40只wister雄性大鼠分为磷酸肌酸钠+阿霉素组干预组(n=10),丹参酮ⅡA磺酸钠+阿霉素干预组(n=10),阿霉素组(n=10)和正常对照组(n=10)。观察大鼠的一般情况,14d处死取心脏标本,用TUNEL法检测各组大鼠心肌细胞凋亡,RT-PCR检测各组大鼠心肌细胞内质网伴侣蛋白GRP78和GRP94的m RNA表达水平。结果 1 TUNEL染色显示与正常对照组相比,阿霉素组大鼠心肌细胞凋亡明显增多(P<0.01);与阿霉素组大鼠相比,磷酸肌酸钠组大鼠心肌细胞凋亡显著减少(P<0.01);与阿霉素组大鼠相比,丹参酮ⅡA磺酸钠组大鼠心肌细胞凋亡减少有统计学意义(P<0.05).2与正常对照组相比,阿霉素组大鼠内质网伴侣蛋白GRP78和GRP94的m RNA表达水平均明显增高(P<0.01),并且其变化趋势与心肌细胞凋亡数相似;与阿霉素组大鼠相比,磷酸肌酸钠组及丹参酮ⅡA磺酸钠组大鼠内质网伴侣蛋白GRP78表达水平明显下降(P<0.01);与阿霉素组大鼠相比,磷酸肌酸钠组大鼠内质网伴侣蛋白GRP94的m RNA表达水平显著下降(P<0.01),而丹参酮ⅡA磺酸钠组大鼠内质网伴侣蛋白GRP94的m RNA表达水平下降有统计学意义(P<0.05)。结论磷酸肌酸钠及丹参酮ⅡA磺酸钠均对阿霉素心肌病大鼠内质网应激介导的心肌细胞凋亡有保护作用。
Objective To investigate the effects of sodium creatine phosphate and sodium tanshinone ⅡA on endoplasmic reticulum stress-induced apoptosis in cardiomyocytes of adriamycin-induced cardiomyopathy rats. Methods Forty wister male rats were randomly divided into sodium phosphate + doxorubicin group (n = 10), tanshinone Ⅱ A sulfonate + doxorubicin group (n = 10), doxorubicin group (n = 10) and normal control group (n = 10). The rats were sacrificed and hearts were sacrificed on day 14. Cardiomyocyte apoptosis was detected by TUNEL method. The m RNA expression of endoplasmic reticulum chaperones GRP78 and GRP94 was detected by RT-PCR. Results 1 TUNEL staining showed that compared with the normal control group, the cardiomyocyte apoptosis in adriamycin group was significantly increased (P <0.01); compared with the doxorubicin group, the myocardial cell apoptosis (P <0.01). Compared with Doxorubicin group, the apoptosis of cardiomyocytes in Tanshinone Ⅱ A sodium sulfonate group was significantly decreased (P <0.05) .2 Compared with the normal control group, Compared with adriamycin group, m RNA expression level of endoplasmic reticulum chaperones GRP78 and GRP94 in adriamycin group was significantly increased (P <0.01), and the change trend was similar to that of myocardial cells; The expression of GRP78, a protein of endoplasmic reticulum, was significantly decreased in sodium creatine phosphate group and sodium tanshinone sodium sulfonate group (P <0.01). Compared with rats in doxorubicin group, endoplasmic reticulum The m RNA expression level of chaperone GRP94 was significantly decreased (P <0.01), while the m RNA expression level of endoplasmic reticulum chaperone GRP94 was significantly decreased in tanshinone Ⅱ A sodium sulfonate group (P <0.05). Conclusion Both sodium creatine phosphate and sodium tanshinone Ⅱ A have a protective effect on endoplasmic reticulum stress-induced cardiomyocyte apoptosis in adriamycin-induced cardiomyopathy rats.