目的 研究積雪草苷(AC)對(duì)在體大鼠心肌缺血再灌注損傷的保護(hù)作用, 初步探討其機(jī)制。方法 40只SPF級(jí)Wistar大鼠, 隨機(jī)分為假手術(shù)組、心肌缺血再灌注模型組及積雪草苷低、中、高劑量組, 每組8只。積雪草苷低、中、高劑量組分別以2.5、5.0、10.0 mL/kg體質(zhì)量的劑量連續(xù)ig藥液14 d, 藥液質(zhì)量濃度1.5 mg/mL。其他各組同時(shí)點(diǎn)ig 0.5%羧甲基纖維素鈉溶液。除假手術(shù)組外, 其他各組結(jié)扎左冠狀動(dòng)脈前降支, 使心肌缺血30 min, 再灌注60 min。用7020全自動(dòng)生化分析儀檢測(cè)血清中超氧化物歧化酶(SOD)、乳酸脫氫酶(LDH)、肌酸激酶同工酶(CK-MB)活性和丙二醛(MDA)水平;ELISA法測(cè)定血清中C反應(yīng)蛋白(CRP);TUNEL法檢測(cè)各組大鼠缺血心肌細(xì)胞凋亡;RT-PCR法檢測(cè)B細(xì)胞白血病/淋巴瘤-2基因(Bcl-2)和與Bcl-2相關(guān)的x蛋白(Bax)的mRNA表達(dá)。結(jié)果 與模型組比較, 積雪草苷各劑量組均能降低血清中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);降低心肌細(xì)胞凋亡指數(shù)(P<0.05);積雪草苷各組凋亡基因Bcl-2表達(dá)水平上升(P<0.05), Bax表達(dá)水平下降(P<0.05), Bcl-2/Bax比值升高(P<0.05)。結(jié)論 積雪草苷預(yù)處理能通過減少心肌細(xì)胞凋亡、抗脂質(zhì)過氧化物產(chǎn)生及抗炎癥反應(yīng)等機(jī)制, 對(duì)心肌缺血再灌注損傷產(chǎn)生保護(hù)作用。

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.

河南省南陽市2012年科技發(fā)展計(jì)劃(2012GG066)