栀子苷对大鼠心肌缺血再灌注损伤保护作用

蔡智慧; 任丽平

doi:10.11847/zgggws2015-31-12-28

栀子苷对大鼠心肌缺血再灌注损伤保护作用

Protective effect of geniposide on myocardial ischemic reperfusion injury in rats

摘要

摘要: 目的探讨栀子苷对大鼠心肌缺血再灌注损伤的保护作用及机制。方法采用结扎左冠状动脉方法制备心肌缺血再灌注损伤动物模型,实验设假手术组、缺血再灌注组、栀子苷(25、50、100 mg/kg)组和阳性对照组;采用试剂盒法检测大鼠血清中乳酸脱氢酶(LDH)、心肌组织超氧化物歧化酶(SOD)、丙二醛(MDA)、Ca²⁺-ATPase水平,TUNEL法检测心肌细胞凋亡率,Western blot法检测心肌细胞p53、Bcl-2和Bax蛋白表达。结果与缺血再灌注组比较,栀子苷50、100 mg/kg组大鼠血清LDH分别为(4598.6±638.7)、(4386.9±549.8)U/L及心肌组织MDA含量分别为(2.12±0.47)、(1.63±0.29)nmol/mgpro明显降低,心肌组织SOD活性分别为(41.48±3.86)、(43.47±3.88)NU/mgpro和Ca²⁺-ATPase水平分别为(0.71±0.11)、(0.72±0.130)mol/mg.h明显增加(P<0.05);TUNEL结果显示,栀子苷50、100 mg/kg组大鼠缺血区心肌细胞凋亡率分别为(12.3±1.8)%、(11.2±1.6)%明显降低(P<0.05);Western blot结果显示,栀子苷50、100 mg/kg组大鼠心肌组织p53蛋白表达分别为(1.71±0.35)、(1.62±0.5)、Bax蛋白表达分别为(0.95±0.24)、(0.89±0.19)明显降低,心肌组织Bcl-2蛋白表达分别为(0.71±0.11)、(0.78±0.170)明显增加(P<0.05)。结论栀子苷对大鼠心肌缺血再灌注损伤具有一定程度保护作用,其机制可能与栀子苷降低氧化应激反应,抑制P⁵³蛋白水平,上调Bcl-2/Bax比率,减少细胞凋亡有关。

Abstract: Objective To explore protective effect of geniposide on myocardial ischemic-reperfusion injury and its mechanism in rats.Methods The myocardial ischemic-reperfusion injury model was made by occluding left coronary artery in rats;then the rats were randomly divided into six groups:pseudo-operation group,ischemic reperfusion(I/R) group,geniposid groups with the dosage of 25,50,and 100mg/kg and a positive control group.The activity of lactate dehydrogenase(LDH) in serum,levels of superoxide dismutase(SOD),maleic dialdehyde(MDA),Ca²⁺-ATPase in myocardial tissues were measured.Myocardial cell apoptosis was marked with terminal-deoxynucleotidyl transferase mediated nick end labeling(TUNEL).The expressions of p53 protein,Bcl-2,and Bax in the myocardial tissues were detected with Western blot.Results Compared with those of the I/R group,significant decreases in LDH(4598.6±638.7 and 4386.9±549.8 U/L)in serum and MDA(2.12±0.47 and 1.63±0.29 nmol/mg.pro) in the myocardial tissues,and significant increases in the concentration of SOD(41.48±3.86 and 43.47±3.88NU/mg.pro) and Ca²⁺-ATPase(0.71±0.11 and 0.72±0.130 mol/mg.h) in the myocardial tissues were observed in the rats treated with geniposid at the dosages of 50 and 100 mg/kg,respectively(all P<0.05).Compared to I/R group,geniposid could promote apoptosis of myocardial cells,with the apoptosis rates of 12.3±1.8% and 11.2±1.6% for the rats treated at the dosages of 50 and 100 mg/kg(both P<0.05).The expressions of p53(1.71±0.35 and 1.62±0.5),Bax(0.95±0.24 and 0.89±0.19)were down-regulated for the rats of geniposid groups at the dosages of 50 and 100 mg/kg(all P<0.05)and the expression level of Bcl-2(0.71±0.11 and 0.78±0.17) was up-regulated for the rats of geniposid groups at the dosages of 50 and 100 mg/kg(all P<0.05).Conclusion Geniposide can reduce oxidative stress induced by myocardial ischemia and reperfusion;the mechanism of the effect maybe relate to the inhibition of p53 protein level,increase of Bcl-2/Bax ratio,and decrease of the occurrence of myocardial cell apoptosis.

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