水飞蓟宾对离体心脏组织缺血再灌注损伤保护作用及机制研究

目的]探讨水飞蓟宾(SIL)对Langendorff灌流大鼠离体心脏缺血再灌注损伤的保护作用及其作用机制。方法] 100只SD大鼠随机分为正常对照组、模型组、SIL低100 mg/(kg·d)]、中200 mg/(kg·d)]、高400 mg/(kg·d)]剂量组,各20只;手术前2h灌胃给药,采用Langendorff灌流系统制备大鼠离体心脏灌注模型,模型组与SIL各组灌注K-H液20 min后停灌30 min、然后再灌注60 min后行各指标检测,而正常对照组持续灌注K-H液。测定冠脉流出液心肌酶活性;通过四氮唑(TTC)染色计算心脏组织梗死面积,采用苏木精-伊红(HE)染色对心脏组织进行病理学检查;测定血流动力学指标;测定抗氧化酶活性和丙二醛(MDA)含量;测定心肌组织Na~+-ATPase、Ca~(2+)-ATPase酶活力。结果 ]与模型组比较,SIL中、高剂量组心肌酶:谷草转氨酶(AST)、乳酸脱氢酶(LDH)、肌酸激酶MB同工酶(CK-MB)活性显著降低,梗死面积显著降低;病理学检查结果显示:经SIL干预能够明显改善心脏组织病变;血流动力学指标明显改善心率(HR)、左室收缩压(LVSP)、左室收缩压最大上升速率(+dP/dtmax)、左室舒张压最大下降速率(-dP/dtmin)显著升高,左室舒张压(LVEDP)显著降低];抗氧化酶:超氧化物歧化酶(SOD)、过氧化氢酶(CAT)活性显著升高且MDA含量显著降低;Na~+-ATPase、Ca~(2+)-ATPase酶活力显著升高,上述结果差异具有统计学意义(P0.05或P0.01)。结论] SIL对离体心脏缺血再灌注损伤具有一定的抑制作用,其作用机制可能与SIL能够改善血液流变学指标、抑制氧化应激、提高ATP酶活力有关。

Protective effect and mechanism of Silibinin on isolated heart tissue ischemia-reperfusion injury

Objective] To study the protective effect of Silybin (SIL) on Langendorff perfusion rat isolated from ischemia-reperfusion injury and study its mechanism.Methods] 100 SD rats were randomly divided into normal control group, model group and SIL low-dose, medium-dose, high-dose100, 200, 400 mg/(kg·d)], n=20. Two hours before surgery, the drugs were given by intragastric administration. The heart perfusion model was established by Langendorff perfusion system, the normal control group continued infusion of K-H solution, model group and salvia miltiorrhiza polyphenolic acid group were perfused 20 min, and then subjected ischemia for 30 min, followed by a 60 min reperfusion period. The myocardial enzyme activity in coronary effluent were determined; TTC staining was used to measure the myocardial infarct size, the cardiac tissue lesions were observed by HE staining; the hemodynamic parameters were determined; the activities of antioxidant enzymes and malondialdehyde (MDA) in myocardium were measured; the activity of Na⁺-ATPase and Ca²⁺-ATPase in myocardium was measured.Results] Compared with model group, the activity of AST, LDH and CK-MB of SIL medium-dose, high-dose were significantly increased; the cardiac tissue infarct size were significantly reduced, cardiac lesions were significantly improved; the hemodynamic parameters were significant improved:the HR, LVSP, +dP/dtmax, -dP/dtmin were significantly increased and LVEDP was significantly decreased; the activity of SOD, CAT in myocardium were significantly increased and the content of MDA were significantly decreased; the activity of Na⁺-ATPase, Ca²⁺-ATPase were significantly increased; all of the difference above were significant (P<0.05 or P<0.01).Conclusion] The SIL has a certain inhibitory effect on isolated heart ischemia-reperfusion injury, which perhaps related to its effects of improving hemorheology, reducing oxidative stress injury and improving ATPase activity.