熊果酸对2型糖尿病大鼠心肌保护作用研究

Study of protective effect of ursolic acid on myocardial injury of type 2 diabetic rats

目的:观察熊果酸对2型糖尿病大鼠心肌保护作用。方法:构建2型糖尿病大鼠模型,成模大鼠随机分为正常对照组、模型对照组、熊果酸低剂量组、熊果酸中剂量组、熊果酸高剂量组和二甲双胍对照组,各组灌胃给予相应药物。给药期间观察各组SD大鼠精神状态、饮食量、尿量等。末次给药麻醉后腹主动脉采血后分离心脏并称质量,计算心质量指数;用全自动生化分析仪测定肌酸激酶(CK)和肌酸激酶同工酶(CK-MB)的活性;ELISA法检测血清和心肌组织中晚期糖基化终产物(AGEs)、肿瘤坏死因子(TNF)-α、超氧化物歧化酶(SOD)和丙二醛(MDA)的水平;心脏组织常规石蜡包埋,HE染色,光镜下观察组织形态学变化。结果:熊果酸高剂量组大鼠血清CK的活性低于模型对照组(P<0.05);熊果酸高剂量组降低2型糖尿病大鼠血清和心脏组织中TNF-α、MDA和AGEs水平以及提高SOD水平效果与二甲双胍组相当,差异无统计学意义(P>0.05)。结论:熊果酸对2型糖尿病大鼠心肌损伤具有保护作用,其机制可能与其降低大鼠血糖、降低AGEs和炎症因子TNF-α水平及改善其氧化应激有关。

Objective:To observe the effects of ursolic acid on cardiomyopathy of type 2 diabetic rats.Methods:The SD rat model with type 2 diabetes mellitus was randomly divided into the control group,model group,low dose of ursolic acid group,middle dose of ursolic acid group,high dose of ursolic acid group and metformin group.Each group was treated with intragastric administration using corresponding drugs,and the mental state,diet quantity and urine volume of SD rat in each group were observed during administration.The blood of abdominal aorta was collected after final administration and anesthesia,the heart was harvested and weighed,and the heart weight index was calculated.The activities of creatine kinase(CK)and creatine kinase isoenzyme(CK-MB)were determined by automatic biochemical analyzer.The serum levels of AGEs,TNF-α,SOD and MDA in myocardium tissue were detected using ELISA.The heart tissue was embedded in paraffin,stained using HE,and the change of issue morphology was observed under the light microscope.Results:The activity of serum CK in high dose of ursolic acid group was lower than that in control group(P<0.05).The high dose of ursolic acid could decrease the levels of TNF-α,MDA and AGEs,and increase the level of SOD in serum and heart tissues in type 2 diabetic rats,the effect of which was similar to that of metformin,and the difference of the effect between high dose of ursolic acid and metformin was not statistically significant(P>0.05).Conclusions:Ursolic acid has protective effect on myocardial injury in rats with type 2 diabetes mellitus,and the mechanism of which may be related to reduce the levels of AGEs and TNF-α,and improve the oxidative stress of rats.