积雪草苷对大鼠心肌缺血再灌注损伤的保护作用研究

目的 研究积雪草苷(AC)对在体大鼠心肌缺血再灌注损伤的保护作用, 初步探讨其机制。方法 40只SPF级Wistar大鼠, 随机分为假手术组、心肌缺血再灌注模型组及积雪草苷低、中、高剂量组, 每组8只。积雪草苷低、中、高剂量组分别以2.5、5.0、10.0 mL/kg体质量的剂量连续ig药液14 d, 药液质量浓度1.5 mg/mL。其他各组同时点ig 0.5%羧甲基纤维素钠溶液。除假手术组外, 其他各组结扎左冠状动脉前降支, 使心肌缺血30 min, 再灌注60 min。用7020全自动生化分析仪检测血清中超氧化物歧化酶(SOD)、乳酸脱氢酶(LDH)、肌酸激酶同工酶(CK-MB)活性和丙二醛(MDA)水平;ELISA法测定血清中C反应蛋白(CRP);TUNEL法检测各组大鼠缺血心肌细胞凋亡;RT-PCR法检测B细胞白血病/淋巴瘤-2基因(Bcl-2)和与Bcl-2相关的x蛋白(Bax)的mRNA表达。结果 与模型组比较, 积雪草苷各剂量组均能降低血清中LDH、CK-MB活性及MDA的量(P<0.05), 升高血清中SOD活性(P<0.05);降低血清中CRP水平(P<0.05);降低心肌细胞凋亡指数(P<0.05);积雪草苷各组凋亡基因Bcl-2表达水平上升(P<0.05), Bax表达水平下降(P<0.05), Bcl-2/Bax比值升高(P<0.05)。结论 积雪草苷预处理能通过减少心肌细胞凋亡、抗脂质过氧化物产生及抗炎症反应等机制, 对心肌缺血再灌注损伤产生保护作用。

Protective effect of asiaticoside on myocardial ischemia-reperfusion injury in rats

Objective To explore the protective effect of asiaticoside (AC) on myocardial ischemia-reperfusion (I/R) injury in rats and study the protective mechanisms. Methods Forty SPF Wistar rats were selected and randomly divided into Sham-operated group (SH group), myocardial I/R model group (I/R group), AC low-dose group (AC-L group), AC middle-dose group (AC-M group), and AC high-dose group (AC-H group), there were eight rats in each group. Rats in the AC-L, AC-M, and AC-H groups were administered with AC at the dose of 2.5, 5.0, and 10.0 mL/kg by ig for 14 d, repectively, with the drug concentration of 1.5 mg/mL. While the rats in the other groups were given 0.5% solution of sodium carboxymethyl cellulose by ig at the same time. Except the rats in the SH group, left anterior descending coronary arteries of rats in other groups were ligated, the time of myocardial ischemia was 30 min, and the time of reperfusion was 60 min. The serum superoxide dismutase (SOD), lactate dehydrogenase (LDH), creatine kinase (CK-MB) activity, and malondialdehyde (MDA) content were detected by 7020 Automatic Biochemical Analyzer; Serum C-reactive protein (CRP) content was measured by ELISA. The ischemic myocardium apoptosis was detected by TUNEL method. The mRNA expressions of B-cell leukemia /lymphoma 2 (Bcl-2) and Bcl-2 associated x protein (Bax) were detected by RT-PCR. Results Compared with the I/R group, AC in each dose group could significantly reduce the levels of LDH, CK, and MDA in serum (P<0.05), obviously elevate the activity of SOD in serum (P<0.05), markedly decrease the level of CRP in serum (P<0.05), and remarkably reduce the index of myocardial apoptosis (P<0.05); AC in each dose group could increase the expression level of Bcl-2, decrease the expression level of Bax, and increase the ratio of Bcl-2 /Bax. Conclusion AC by pretreatment has the protective effect on myocardial I/R injury in rats, the mechanisms may be related with reducing the myocardial apoptosis, anti-lipid peroxides, and anti-inflammatory.