护心康对TLR4基因敲除小鼠动脉粥样硬化模型Wnt1的影响

Effect of Huxinkang (护心康) on Wnt1 in TLR4^(-/-) Mice Atherosclerosis Model

目的:探讨TLR4基因敲除小鼠动脉粥样硬化时Wnt1的变化及护心康的干预作用。方法:SPF级TLR4基因敲除小鼠共70只,随机取12只为正常组,予以普通饲料喂养;其余58只予以高脂饲料造模,喂养13周后从造模动物中随机选取5只,观察胸主动脉,光镜下发现粥样斑块为造模成功。造模成功动物随机分为模型组、护心康组、Wnt抑制剂WIF组、阿托伐他汀组,每组12只,分别予以相应处理。干预8周后处死小鼠取胸主动脉,光镜下观察动脉粥样硬化形成情况;免疫组化法检测斑块中Wnt1蛋白的表达。结果:(1)光镜观察:正常组未见动脉粥样硬化;模型组可见动脉内膜增厚,粥样斑块形成,血管腔减小;各药物干预组斑块病变相对较轻。(2)Wnt1蛋白表达:高脂造模后,模型组中Wnt1蛋白表达明显高于正常组(P<0.01);治疗后Wnt1表达明显下降,与模型组比较,WIF组降低显著(P<0.01),护心康组和阿托伐他汀组的Wnt1表达均降低(P<0.05);WIF治疗后,Wnt1降低较其他治疗组明显(P<0.05),护心康组和阿托伐他汀组Wnt1表达比较,差异无统计学意义(P>0.05)。结论:Wnt1在TLR4基因敲除小鼠动脉粥样硬化斑块中表达升高,护心康能降低Wnt1的表达,从而可以减轻动脉粥样硬化的形成。

Objective:To investigate the changes of Wnt1 in TLR4-/-mice of atherosclerosis and the intervention of Huxinkang.Methods:A total of 70 SPF TLR4-/-mice were fed,and 12 mice of them were randomly selected as control group and fed with normal diet.The remaining 58 mice were modeled with high-fat diet.After 13 weeks of feeding,5 mice were randomly selected from them to observe the thoracic aorta,and atheroma plaque was found under light microscopy indicating successful modeling.The successful model animals were randomly divided into model group,HuxinKang group,Wnt inhibitor WIF group and atorvastatin group,10 mice in each group,which were treated accordingly.Eight weeks after the treatment,the mice were sacrificed and the thoracic aorta was taken.The formation of atherosclerosis was observed under light microscope.The expression of Wnt1 proteins in plaques was detected by immunohistochemistry.Results:(1)Light microscopy:no atherosclerotic plaques were formed in the control group.A large number of plaques were formed in the model group,and the intima thickened,so the vascular lumen was significantly reduced;The plaque lesions in each drug intervention group were relatively light.(2)Wnt1 protein expression:After being fed with high-fat,the model group showed higer expression of Wnt1 than the control groups(P<0.01).The expression of Wnt1 was significantly decreased after treatment.The Wnt inhibitor WIF group showed lower expression of Wnt1 than the model group(P<0.01),and the Wnt1 expression in the Xinxinkang group and the atorvastatin group was also significantly decreased(P<0.05).Wnt inhibitor Wnt1 decreased significantly compared with other treatment groups(P<0.05),and there was no significant difference between the expression of Huxinkang group and atorvastatin(P>0.05).Conclusion:The expression of Wnt1 is increased in atherosclerotic plaques in TLR4-/-mice atherosclerosis model;Huxinkang can reduce the expression of Wnt1,thereby reducing the formation of atherosclerosis.