目的 观察人参三醇皂苷(PTS)对大鼠心肌缺血再灌注损伤(MIRI)的保护作用及其机制。方法 Wistar大鼠,随机分为6组:假手术组、模型组、阳性药组、PTS(22.5、45、90 mg/kg)组。采用结扎冠状动脉左前降支(LAD)的方法制备大鼠MIRI模型,缺血30 min再灌24 h;手术前ip给药,连续7 d;观察给予PTS后MIRI大鼠心电图ST段和血清肌酸激酶同工酶(CK-MB)、心肌肌钙蛋白I(cTnI)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)水平及心肌梗死面积、心肌组织病理、心肌细胞超微结构的改变。实时定量PCR检测心肌组织Nrf2和血红素氧合酶(HO-1)基因表达水平。结果 与模型组比较,45、90 mg/kg PTS能显著降低MIRI模型大鼠ST段和血清CK-MB、cTnI、IL-6、TNF-α水平,改善心肌形态结构的损伤程度,增加心肌组织Nrf2和HO-1基因表达水平。结论 PTS对MIRI大鼠心肌具有保护作用,其作用机制可能是通过上调Nrf2及其下游靶基因HO-1表达,抑制缺血再灌注所致的心肌炎性反应。

Objective To observe the effects of panaxtriol saponin (PTS) on CK-MB, cTnI, IL-6, TNF-α, and ultrastructure against myocardial ischemia-reperfusion injury (MIRI) in rats. Methods Wistar rats were randomly divided into six groups: Sham, MIRI model, positive control, and 22.5, 45, and 90 mg/kg PTS groups. Animal MIRI model was made by ligating the left anterior descending coronary artery. Drug was given for seven consecutive days before the operation by ip injection. Rats were sacrificed after 30 min ischemia and 24 h reperfusion. CK-MB, cTnI, IL-6, and TNF-α in serum were measured and the changes of myocardial ultrastructure were observed. Real time PCR was used to evaluate change of NRF2 and HO-1 mRNA level in myocardial tissue. Results Compared with model, PTS 45 and 90 mg/kg reduced the CK-MB, cTnI, IL-6, and TNF-α in serum and improve the myocardium ultrastructure. Nrf2 and HO-1 mRNA levels in PTS treatment group were higher than those in MIRI model group. Conclusion PTS plays a crucial role in cardioprotection against the ischemia and reperfusion injury in rats. The protective mechanism suggests that PTS could stimulate NRF2/HO-1 expression in myocardial tissue and then inhibit myocardial inflammation.

国家“十一五”科技支撑计划项目(2007BAI38B04)