参元丹优化方对动脉粥样硬化小鼠胰岛素抵抗及血清血栓素A2/前列环素比值和DNA甲基化水平的影响

Effects of Optimum Shenyuandan Decoction on Insulin Resistance,Serum TXA_2/PGI_2 Ratio and DNA Methylation Level of Mice with Atherosclerosis

目的观察参元丹优化方对高脂喂养Apo E基因敲除(Apo E-/-)小鼠动脉粥样硬化(AS)胰岛素抵抗及血清血栓素A2(TXA2)/前列环素(PGI2)比值和DNA甲基化(5-m C)水平的影响,探讨其相关作用机制。方法 40只8周龄雄性Apo E-/-小鼠高脂饲料喂养6周,随机分为模型组、立普妥组、参元丹原方组和参元丹优化方组,各给药组给予相应药物干预6周。检测小鼠血清总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、胰岛素、TXA2、PGI2、DNA甲基化转移酶(DNMT1)和5-m C水平。HE染色,图像分析测量小鼠主动脉AS斑块面积。结果与模型组比较,参元丹原方组和参元丹优化方组小鼠血清TC和TG水平明显降低,HDL-C水平明显升高(P<0.01),AS指数明显降低,校正后主动脉AS斑块面积显著降低(P<0.05),参元丹优化方组小鼠血清5-m C、DNMT1、胰岛素水平及TXA2/PGI2比值显著降低(P<0.05),参元丹优化方组优于参元丹原方组(P<0.01)。结论参元丹优化方降低血清胰岛素、5-m C水平和TXA2/PGI2比值均优于原方,改善血脂和AS效果与原方相当。

Objective To investigate the effects of optimum Shenyuandan Decoction on insulin resistance,serum TXA2/PGI2 ratio and 5-mC level of ApoE-/-mice with atherosclerosis(AS)fed with high fat diet;To discuss the related mechanism of action.Methods Totally forty 8 week-old male ApoE-/-mice were fed with high fat diet for 6 weeks.They were randomly divided into model group,Lipitor group,Shenyuandan Decoction group and optimum Shenyuandan Decoction group.Each group was given relevant medicine for intervention for 6 weeks.Serum TC,TG,LDL-C,HDL-C,insulin,TXA2,PGI2,DNMT1 and 5-mC level were measured.HE staining and image analysis were used to measure the AS plaque area of the mouse aorta.Results Compared with the model group,the serum levels of TC and TG in Shenyuandan Decoction group and optimum Shenyuandan Decoction group decreased significantly,the level of HDL-C increased significantly(P<0.01);the AS index decreased significantly and the area of the AS plaque in the aorta decreased significantly(P<0.05).The serum levels of 5-mC,DNMT1,insulin and the ratio of TXA2/PGI2 in optimum Shenyuandan Decoction group decreased significantly(P<0.05),and optimum Shenyuandan Decoction group was better than Shenyuandan Decoction group(P<0.01).Conclusion Optimum Shenyuandan Decoction is superior to Shenyuandan Decoction in reducing the serum insulin,5-mC level,and the ratio of TXA2/PGI2,and the effect is equivalent to Shenyuandan Decoction in improving blood lipid and AS.