ATRA对糖尿病大鼠心肌内iNOS表达的影响

目的:动态观察糖尿病(DM)大鼠心肌组织内诱生型一氧化氮合酶(iNOS)表达水平的变化及全反式维甲酸对其的干预作用。方法:链脲佐菌素(STZ)法复制SD大鼠实验性1型DM模型,并随机分为全反式维甲酸ATRA,20 mg/(kg.d)]处理组或非ATRA处理组。造模型后30 d及60 d测量空腹血糖、心重/体重比值,HE染色观察心肌结构的改变,并用RT-PCR技术和免疫组化技术检测心肌组织中iNOS表达水平。结果:30 d和60 d时,DM大鼠心肌内iNOS表达率增加(P<0.05);ATRA处理后可以使心肌内iNOS表达率下降(P<0.05),而DM组和ATRA组大鼠血糖无明显差异(P>0.05)。结论:DM大鼠心肌内iNOS表达率增加,可能与高糖状态下心肌病变有关。ATRA处理后可以使心肌内iNOS表达率下降,这与延缓高糖状态下心肌病变有关。同时说明糖尿病心肌病的发生发展与iNOS再表达密切相关。

Effects of All-Trans Retinoic Acid on the iNOS Expression in Myocardium of Diabetic Rats

Objective: To study the effect of all-trans retinoic acid(ATRA) on the expression of the nitricoxide synthase(iNOS) in the left ventricle of the diabetic rat.Methods: Diabetes models were induced by streptozotocin(STZ,60 mg per kg body weight intravenously).The levels of blood glucose were measured before STZ injection and at 48-72 h after STZ injection and at the end of experiment.Levels of blood glucose ≥16.7 mmol/L means success of the model,and all models were assigned to the ATRA treatment group(ATRA 20 mg/(kg·d)) and non-treatment group.Specimens were taken from left ventrcle of the rats at 30 or 60 d after the models were established for the observation of myocardium histomorphology and determining the expression of iNOS by RT-PCR.The heart weight and body weight was recorded as well.Results: Levels of blood glucose significantly increased in the diabetic rats and the ATRA treatment rats than the control rats.At 30 and 60 d,heart/body weight ratio significantly increased in diabetic rats than that of the control rat(P<0.05),but ATRA treatment decreased the ratio in diabetic rats(P<0.05).The myocardium histomorphology changed markedly in diabetic rats,but ATRA mitigated the change.Levels of iNOS in myocardium increased in diabetic rats than in control rats(P<0.05),but ATRA also decreased the levels of iNOS expression in diabetic rats(P<0.05),and the level of blood glucose is not different between ATRA group and non-ATRA treatment group.Conclusion: The expression of iNOS increases in diabetic rats and ATRA might inhibit the expression.This study shows a possible relatioship between iNOS and cardiomyopathy of diabetes mellitus.