奥拉西坦对心肌缺血/再灌注损伤的保护作用

、Protective role of oxiracetam in rats after myocardial ischemia reperfusion injury

摘要:

目的 研究奥拉西坦对心肌缺血/再灌注损伤(MI/RI)的保护作用及其机制。方法 32只大鼠依据随机数表法分为4组,每组8只:(1)假手术组；(2)MI/RI组；(3)低剂量组(奥拉西坦30mg/kg)；(4)高剂量组(奥拉西坦50mg/kg)。低剂量组和高剂量组的16只大鼠手术前除正常饲养外,通过灌胃方式给予对应剂量的奥拉西坦,1次/d,连续7d。结扎大鼠冠状动脉前降支,建立MI/RI模型。酶联免疫吸附测定大鼠血清中肌酸激酶同工酶MB(CK-MB)、乳酸脱氢酶(LDH)、超氧化物歧化酶(SOD)、白细胞介素-6(IL-6)和丙二醛(MDA)。测定心肌梗死面积百分比、心肌细胞凋亡率和Bcl-2/Bax比值。采用SPSS 21.0软件进行统计分析。组间比较采用单因素方差分析。结果 与MI/RI组比较,低剂量组和高剂量组大鼠的心肌梗死面积百分比(36.2%和13.6%和22.3%)、心肌细胞凋亡率(45.4%和30.6%和21.3%)、血清中CK-MB[(97.50±8.54)和(75.24±5.62)和(63.10±7.23)U/L]、LDH[(900.02±57.74)和(660.62±49.84)和(577.37±54.09)U/L]、MDA[(88.84±3.26)和(66.47±6.25)和(57.08±4.99)U/L]和IL-6[(186.39±10.18)和(153.34±6.81)和(143.31±9.08)pg/ml]含量均显著降低(P<0.05),而SOD[(15.22±1.24)和(24.80±3.32)和(34.82±3.66)U/ml]和Bcl-2/Bax比值(0.19和0.47和1.16)显著增加(P<0.05)。结论 奥拉西坦可能通过减轻氧化应激反应来抑制线粒体途径的细胞凋亡来保护MI/RI的心肌。

Abstract:

Objective To investigate the protective role of oxiracetam in rats after myocardial ischemia-reperfusion injury (MI/RI) and its underlying mechanism. Methods A total of 32 Sprague-Dawley (SD) rats were randomly divided into 4 groups, with 8 rats in each group, that is, sham operation group (Sham group), MI/RI group, and low- and high-dose groups (30 and 50 mg/kg oxiracetam respectively). In addition to normal feeding before surgery, the rats from the two treatment groups were given the corresponding dose of oxiracetam by gavage for once per day for 7 consecutive days. Then the anterior descending coronary artery was ligated in the rats of the latter 3 groups to establish the MI/RI model. Serum contents of lactate creatine kinase isoenzyme MB (CK-MB), lactate dehydrogenase (LDH), interleukin-6 (IL-6), superoxide dismutase (SOD) and malondialldehyde (MDA) were measured with enzyme linked immunosorbent assay (ELISA). The percentage of myocardial infarction area, apoptosis rate of myocytes and the ratio of Bcl-2/Bax in myocardial tissue were measured and calculated. SPSS statistics 21.0 was used for statistical analysis. One-way ANOVA was employed for inter-group comparisons. Results The low- and high-dose groups had significantly lower percentage of myocardial infarction area (13.6% vs 22.3% vs 36.2%), apoptosis rate of myocytes (30.6% vs 21.3% vs 45.4%), and serum contents of CK-MB [(75.24±5.62) vs (63.10±7.23) vs (97.50±8.54)U/L], LDH [(660.62±49.84) vs (577.37±54.09) vs (900.02±57.74)U/L], MDA [(66.47±6.25) vs (57.08±4.99) vs (88.84±3.26)U/L] and IL-6 [(153.34±6.81) vs (143.31±9.08) vs (186.39±10.18)pg/ml], but obviously elevated serum SOD content [(24.80±3.32) vs (34.82±3.66) vs (15.22±1.24)U/ml] and Bcl-2/Bax ratio (0.47 vs 1.16 vs 0.19) when compared with the MI/RI group (all P<0.05). Conclusion Oxiracetam can protect MI/RI by attenuating oxidant stress response and suppressing mitochondrial pathway of apoptosis.