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目的研究积雪草苷(asiaticoside,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(SH组)、心肌缺血再灌注模型组(IR组)、积雪草苷低剂量组(ACL组)、积雪草苷中剂量组(AC-M组)及积雪草苷高剂量组(AC-H组),各8只。积雪草苷低、中、高剂量组分别以0.25、0.50、1.00 ml/100g体重的剂量连续灌胃14 d,药液浓度1.5 mg/ml。其它各组以0.5%羧甲基纤维素钠溶液灌胃。除SH组外,其它各组结扎左冠状动脉前降支,使心肌缺血30 min,再灌注60 min。检测血清中超氧化物歧化酶(superoxide dismutase,SOD)、乳酸脱氢酶(lactic acid dehydrogenase,LDH)、肌酸激酶(creatine kinase,CK)活性和丙二醛(malondialdehyde,MDA)含量;ELISA法测定血清中C反应蛋白(C-reactive protein,CRP)含量;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(B-cell leukemia/lymphoma 2,Bcl-2)和与Bcl-2相关的x蛋白(Bcl-2 associated x protein,Bax)的m RNA表达。计量资料两组间比较采用t检验,多组间比较采用单因素方差分析,P<0.05为差异有统计学意义。结果与IR组比,积雪草苷各剂量组均能降低血清中LDH、CK-MB活性及MDA含量,升高血清中SOD活性,降低血清中CRP含量,降低心肌细胞凋亡指数,差异均有统计学意义(均P<0.05)。积雪草苷各组凋亡基因Bcl-2表达水平上升,Bax表达水平下降,Bcl-2/Bax比值升高,差异均有统计学意义(均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。
Objective To study the protective effect of asiaticoside (AC) on myocardial ischemia-reperfusion injury in vivo and its mechanism. Methods Forty SPF Wistar rats were randomly divided into sham operation group (SH group), ischemia reperfusion model group (IR group), asiaticoside low dose group (ACL group), asiaticoside medium dose (AC-M group) and asiaticoside high-dose group (AC-H group), each with 8 rats. Centella asiatica low, medium and high dose groups were 0.25, 0.50,1.00 ml / 100g body weight of continuous gavage 14 d, liquid concentration 1.5 mg / ml. The other groups were orally gavaged with 0.5% sodium carboxymethylcellulose solution. Except SH group, the other groups were ligated left anterior descending coronary artery, myocardial ischemia 30 min, reperfusion 60 min. Serum levels of superoxide dismutase (SOD), lactate dehydrogenase (LDH), creatine kinase (CK) and malondialdehyde (MDA) Serum levels of C-reactive protein (CRP) were measured. TUNEL method was used to detect the apoptosis of ischemic myocardium in each group. The levels of B-cell leukemia / lymphoma 2, Bcl-2) and Bcl-2 associated x protein (Bax). Measurement data between the two groups using t test, multiple groups were compared using one-way analysis of variance, P <0.05 for the difference was statistically significant. Results Compared with the IR group, all the asiaticoside groups could reduce the activity of LDH, CK-MB and the content of MDA in the serum, increase the activity of SOD in serum, decrease the content of CRP in serum and decrease the index of apoptosis of cardiomyocytes There was statistical significance (all P <0.05). Asiaticoside could up-regulate the expression of Bcl-2, Bax and Bcl-2 / Bax, all of which were significantly different (all P <0.05). Conclusion Asiaticoside preconditioning can protect myocardium against ischemia-reperfusion injury by decreasing myocardial apoptosis, anti-lipid peroxidation and anti-inflammation mechanisms.