熊果酸对急性心肌梗死小鼠氧化应激和脂质代谢的影响

The effect of ursolic acid on oxidative stress and lipid metabolism in mice with acute myocardial infarction

目的 观察熊果酸对急性心肌梗死小鼠心肌的保护作用机制。 方法 30只C57小鼠随机均分为假手术组、急性心肌梗死模型组和熊果酸组。熊果酸组和急性心肌梗死模型组结扎冠状动脉左前降支6 h,收集各组小鼠心脏和血清。硝基四氮唑（NBT）染色检测心肌梗死面积,HE染色检测心肌病理形态,全自动生化分析仪检测血清乳酸脱氢酶（LDH）、磷酸肌酸激酶（CPK）、心肌肌钙蛋白I（cTnI）、甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDLC）、高密度脂蛋白胆固醇（HDLC）水平,硫代巴比妥酸（TBA）法检测心肌丙二醛（MDA）、脂质过氧化物（LPO）和游离脂肪酸（FFA）含量,黄嘌呤氧化酶法检测心肌过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GPx）和超氧化物歧化酶（SOD）活性,放射免疫法检测血浆6-酮-前列腺素F1α（6-Keto-PGF1α）及血栓素A2（TXA2）含量。 结果 与假手术组相比,急性心肌梗死模型组心肌梗死面积、血清LDH、cTnI、CPK、TC、TG及LDLC水平、心肌LPO和MDA含量、血浆TXA2、心肌梗死区和非梗死区FFA含量以及心肌病理形态改变均明显增加,但血清CAT、GPx和SOD活性以及HDLC和6-Keto-PGF1α含量均明显减少。与急性心肌梗死模型组相比,熊果酸组心肌梗死面积、血清LDH、cTnI、CPK、TC、TG和LDLC水平、心肌LPO和MDA含量、血浆中TXA2、心肌梗死区和非梗死区FFA含量以及心肌病理形态改变均明显减少,而血清CAT、GPx和SOD活性以及HDLC和6-Keto-PGF1α含量均明显增加。 结论 熊果酸对急性心肌梗死有明显的保护作用,其作用机制与抑制氧化应激损伤和改善脂质代谢紊乱相关。

Aim To explore the protective effect and potential mechanism of ursolic acid （UA） on acute myocardial infarction （AMI） in mice. Methods 30 C57 mice were randomly divided into sham group, AMI model group and ursolic acid group. AMI model group and ursolic acid group were ligating left anterior descending artery for 30 min. The myocardial and serum in the three groups were collected after reperfusion for 4 h. NBT and HE were used to evluate the myocardial infarct size and myocardial pathological changes, respectively; automatic biochemical analyzer test was used to detect the expression of creatine phosphokinase （CPK）, cardiac troponin I （cTnI）, triglyceride （TG）, total cholesterol （TC）, low density lipoprotein cholesterol （LDLC） and high density lipoprotein cholesterol （HDLC） in the serum; thiobarbituric acid （TBA） method was used to examine myocardial malondialdehyde （MDA）, lipid peroxide （LPO） and free fatty acid （FFA）; enzyme xanthine oxidase method was used to detect the activity of catalase （CAT）, glutathione peroxidase （GPx） and superoxide dismutase （SOD） in the heart; the activity of plasma 6-Keto prostaglandin F1α（6-Keto-PGF1α） and the content of thromboxane A2 （TXA2） was detected by radiation immunoassay in plasma. Results Compared with sham group, AMI model group had higher myocardial infarct size, more myocardial pathological changes and higher expression of LDH, cTnI, CPK, TC, TG, LDLC, MDA, LPO, TXA2 and the content of FFA in myocardial infarction area and non infarct area with lower activity of CAT, GPx, SOD and the expression of 6-Keto-PGF1α and HDLC. Compared with AMI model group, ursolic acid group had lower myocardial infarct size, less myocardial pathological changes and lower expression of LDH, cTnI, CPK, TC, TG, LDLC, MDA, LPO, TXA2 and the decreased content of FFA in myocardial infarction area and non infarct area with higher activity of CAT, GPx, SOD and expression of 6-Keto-PGF1α and HDLC. Conclusion Ursolic acid had an obvious protective effect on acute myocardial infarction, and its mechanism was related to the inhibition of oxidative stress and the improvement of lipid metabolism disorder.