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目的:探讨α-硫辛酸(α-lipoic acid)抗氧化作用及抗心肌细胞凋亡对慢性心力衰竭大鼠心功能的影响。方法:用急性心肌梗死(acute myocardial infarction,AMI)后大鼠心功能异常的方法构建慢性心力衰竭(chronic heart failure,CHF)模型,6周龄的雄性SD大鼠随机分为α-硫辛酸处理组(AMI+α-硫辛酸,n=15)、对照组(AMI+NS,n=14)和假手术组(sham-operated+NS,n=10)。术后2周后α-硫辛酸处理组给予硫辛酸[60 mg/(kg·d)]腹腔注射,其余组大鼠等量生理盐水(normal saline,NS)腹腔注射。4周后,采用超声心动图分析各组大鼠的心功能、ELISA法检测血浆脑钠尿肽(brain natriuretic peptide,BNP)含量、超氧化物歧化酶(superoxide dismutase,SOD)、总抗氧化能力(total antioxidant capacity,TAC)、丙二醛(malondialdehyde,MDA)含量、HE染色观察心肌细胞形态、免疫组化法分析心肌诱导型氧化亚氮合酶(induciblenitric oxidesynthase,i NOS)的表达、Western blot法测大鼠心肌组织c-Jun氨基末端激酶(c-Jun N-terminal kinase,JNK)及Caspase-12蛋白含量。结果:对照组与假手术组大鼠相比,大鼠心功能明显降低(射血分数由90.16%降至66.84%),血清BNP、MDA水平明显升高(P<0.05),SOD、TAC水平降低(P<0.05);HE染色显示心肌组织明显水肿、排列紊乱,i NOS表达升高(P<0.05),证明CHF建模成功;α-硫辛酸处理组与对照组相比,大鼠的心功能明显改善(射血分数由66.84%升至80.15%),BNP、MDA含量、i NOS、JNK、Caspase-12蛋白表达均下降(P<0.05),TAC、ROS水平升高(P<0.05)。结论:CHF建模成功,α-硫辛酸可通过抗氧化和减少细胞凋亡的方式改善CHF大鼠的心功能。
Objective: To investigate the effects of α-lipoic acid on cardiomyocyte apoptosis and cardiomyocyte apoptosis in rats with chronic heart failure. Methods: The model of chronic heart failure (CHF) was established by abnormal cardiac function in rats after acute myocardial infarction (AMI). Six-week-old male Sprague-Dawley rats were randomly divided into α-lipoic acid Groups (AMI + α-lipoic acid, n = 15), control group (AMI + NS, n = 14) and sham-operated + NS (n = 10). After 2 weeks, α-lipoic acid was given intraperitoneally to 60 mg / (kg · d) of lipoic acid, and the other rats were injected intraperitoneally with normal saline (NS). After 4 weeks, the cardiac function of rats in each group was analyzed by echocardiography. The levels of plasma BNP, superoxide dismutase (SOD), total antioxidant capacity The total antioxidant capacity (TAC) and malondialdehyde (MDA) contents were observed. The morphology of myocardial cells was observed by HE staining. The expression of inducible nitric oxide synthase (iNOS) was detected by immunohistochemistry. Western blot The content of c-Jun N-terminal kinase (JNK) and Caspase-12 protein in myocardium of rats were measured by the method. Results: Compared with sham operation group, the heart function of rats in control group was significantly decreased (ejection fraction decreased from 90.16% to 66.84%), serum BNP and MDA levels were significantly increased (P <0.05), while SOD and TAC levels (P <0.05). HE staining showed significant edema, disorganized myocardial i NOS expression (P <0.05), indicating that CHF modeling was successful; α-lipoic acid treatment group compared with the control group, the rat (P <0.05), and the levels of TAC and ROS increased (P <0.05), and the heart function improved markedly (ejection fraction rose from 66.84% to 80.15%), BNP and MDA contents, iNOS, JNK and Caspase- ). CONCLUSIONS: CHF was modeled successfully and α-lipoic acid may improve cardiac function in CHF rats by means of antioxidation and reduction of apoptosis.