化痰散结法对ApoE-/-小鼠血脂及动脉粥样硬化的影响

Effect of the method of resolving phlegm and dispersing stasis on blood lipids and atherosclerosis in ApoE-/-mice

[目的]探讨化痰散结方剂内消软脉汤2号对ApoE-/-小鼠血脂及动脉粥样硬化的影响,并探讨其作用机制。[方法]随机将30只ApoE-/-小鼠平均分为3组,通过高脂饮食喂养16周以建立动脉粥样硬化模型,同步给予蒸馏水、内消软脉汤2号低剂量[2.1 g/(kg·d)]、高剂量[4.2 g/(kg·d)]灌胃处理16周,生化法检测血脂4项,苏木精-伊红(HE)染色观察主动脉斑块、肩胛脂肪组织及肝脏的形态学,蛋白免疫印迹法(Western Blot)检测肩胛脂肪组织解偶联蛋白1(UCP1)及肝脏低密度脂蛋白受体(LDLR)的表达情况,以评估内消软脉汤2号改善动脉粥样硬化及降脂的作用,并初步探讨其作用机制。[结果]与对照组比较,内消软脉汤2号低剂量及高剂量组主动脉斑块面积均减少,低剂量组血清低密度脂蛋白胆固醇(LDL-C)、总胆固醇(TC)下降,差异具有统计学意义(P<0.05);高密度脂蛋白胆固醇(HDL-C)呈升高趋势(P>0.05);高剂量组血清LDL-C及TC呈下降趋势(P>0.05)、HDL-C呈升高趋势(P>0.05)。油红O染色结果表明,低剂量与高剂量组的肝脂肪变性均明显改善。HE染色结果表明,低剂量与高剂量组的肩胛脂肪组织被活化。Western Blot结果显示,低剂量组及高剂量组均可使肝脏LDLR和肩胛脂肪组织的UCP1表达升高,差异具有统计学意义(P<0.05)。[结论]化痰散结法可改善ApoE-/-小鼠的动脉粥样硬化及高脂血症,其潜在作用机制可能为上调肝脏LDLR及肩胛脂肪组织UCP1的表达。

[Objective]To explore the effect of Neixiao Ruanmai Decoction No.2 of Huatan sanjie treatment,a prescription for resolving phlegm and dispersing stasis,on blood lipids and atherosclerosis in ApoE-/-mice,and explore its mechanism.[Methods]The 30 ApoE-/-mice were randomly divided into three groups on average.They were fed with high-fat diet for 16 weeks to establish atherosclerosis model.They were simultaneously given distilled water,low-dose[2.1 g/(kg·d)]and high-dose[4.2 g/(kg·d)]of Neixiao Ruanmai Decoction No.2 by gavage for 16 weeks.Four items of blood lipid were detected by biochemical method.The morphology of aortic plaque,scapular adipose tissue and liver were observed by HE staining,Western blot method was used to detect the expression of uncoupling protein1(UCP1)in scapular adipose tissue and low-density lipoprotein receptor(LDLR)in liver to evaluate the effect of Neixiao Ruanmai Decoction No.2 on improving atherosclerosis and lowering blood lipid,and to preliminarily explore the mechanism of action of the drug.[Results]Compared with the control group,the area of aortic plaque in the low-dose and high-dose groups of Neixiao Ruanmai Decoction No.2 decreased,while the serum LDL-C and TC in the low-dose group decreased(P<0.05)and HDL-C increased(P<0.05);In the high-dose group,serum LDL-C and TC decreased(P>0.05)and HDL-C increased(P<0.05).The results of oil red O staining showed that the liver steatosis in both low and high dose groups significantly improved.The results of HE staining showed that the scapular adipose tissue of low and high dose groups was activated.Western blot results showed that both low-dose and high-dose groups could increase the expression of UCP1 in liver LDLR and scapular adipose tissue(P<0.05).[Conclusion]Huatan Sanjie treatment can improve the atherosclerosis and hyperlipidemia of ApoE-/-mice,and up-regulate the expression of LDLR in liver and UCP1 in scapular adipose tissue may be its potential mechanism.