化痰活血法对ApoE(-/-)小鼠主动脉胆固醇逆向转运相关蛋白表达的影响

Effects of methods of elimating phlegm and activating blood circulation on reverse cholesterol transport in apolipoprotein E gene knocked-out mice

目的:观察化痰活血法对ApoE基因敲除[ApoE(-/-)]小鼠主动脉胆固醇逆转运(RCT)主要相关蛋白小凹蛋白-1(caveolin-1)、清道夫受体BI(SR-BI)的影响。方法:4～6周龄ApoE(-/-)小鼠高脂饲料喂养16周后,分为化痰组、活血组、化痰活血组、普伐他汀组和模型对照组;另5周龄正常C57BL/6J家系小鼠10只,高脂饲料喂养16周,设为正常对照组。化痰组灌服小陷胸汤加枳壳水提液2.5 mL/100 g体质量,活血组灌服芎芍胶囊0.05 g/100 g体质量,化痰活血组灌服小陷胸汤加枳壳水提液2.5 mL/100 g体质量+芎芍胶囊0.05 g/100 g体质量,普伐他汀组灌服普伐他汀0.3 mg/100 g体质量;模型对照组及正常对照组均灌服生理盐水1 mL/100 g体质量,连续给药16周。取主动脉常规石蜡切片光镜下观察,测量动脉面积及斑块面积;免疫组化观察caveolin-1、SR-BI表达。结果:在高脂刺激下,ApoE(-/-)小鼠主动脉caveolin-1及SR-BI表达均有所增加(P<0.01);普伐他汀组、化痰组、活血组及化痰活血组均可显著提高ApoE(-/-)小鼠主动脉caveolin-1及SR-BI的表达,组间比较显示化痰活血组caveolin-1及SR-BI表达显著高于单纯化痰组和活血组(P<0.05,P<0.01)。活血、化痰以及活血化痰三种治法均可显著减缓ApoE(-/-)小鼠主动脉粥样硬化病变程度,效果与普伐他汀相当。结论:活血、化痰或活血化痰法均可提高caveolin-1和SR-BI的表达,促进RCT过程,减少ApoE(-/-)小鼠主动脉粥样硬化斑块形成,其中活血化痰组在促进胆固醇逆向转运方面优于单纯活血组或化痰组。

Objective：To explore the effect of methods of elimating phlegm and activating blood circulation on expression of caveolin-1 and scavenge receptor class B type I（SR-BI） about reverse cholesterol transport（RCT） in apolipoprotein E gene knocked-out[ApoE（-/-）] mice. Methods：ApoE（-/-） mice at the age of 4-6 weeks old were fed with hypcrlipidemic diet,while 10 C57BL/6J mice were fed normally. After 16 weeks,ApoE（-/-） mice were classified into elimating phlegm group,activating blood circulation group,elimating phlegm and activating blood circulation group ,pravachol group,and model group. C57BL/6J mice were also used as normal control group. Elimating phlegm group was given modified Xiaoxianxiong formula 2.5 mL/100 g weight,activating blood circulation group was given Xiongshao capsule 0.05 g/100 g weight,elimating phlegm and activating blood circulation group was given modified Xiaoxianxiong formula 2.5 mL/100 g weight and Xiongshao capsule 0.05 g/100 g weight,pravachol group was given pravachol 0.3 mg/100g weight,model group and the normal control group were given normal saline. After 16 weeks, The paraffin sections of aortas from mice were observed under optical microscope. Arterial size and plaque area were detected. Cavolin-1 and SR-BI expression were detected by immunohistoehemstry. Results：Compared with the C57 sharing with the same genetic background,the positive rate of ApoE（-/-） mice aorta eaveolin-1 and SR-BI in- creased（P〈0.01）. In different group of elimating phlegm,activating blood circulation and pravachol group compared with model group,the level of caveolin-1 and SR-BI increased（P〈0.05）. Compared with elimating phlegm group and activating blood circulation group,the level of caveolin-1 and SR-BI increased in elimating phlegm and activating blood circulation group（P〈0.05,P〈0.01）. Chinese herbal compound groups can alleviate the ApoE（-/-） mice atherosclerotic plaque,in which effect as same as that of pravachol group. Conclusion：Methods of elimatingphlegm or/and activating blood circulation can obviously promote the expression of ApoE（-/-） mice aorta caveolin-1 and SR-BI,to promote the RCT in ceils of aorta,and obviously reduce the formation of aorta atherosclerotic plaque of ApoE（-/-） mice. Methods of elimating phlegm and activating blood circulation is better than methods of elimating phlegm or methods of activating blood circulation.