消瘀泄浊饮对慢性肾衰竭动脉粥样硬化大鼠主动脉泛素-蛋白酶体通路组分表达的影响

Effects of Xiaoyu Xiezhuo Decoction(消瘀泄浊饮)on Expressions of Ubiquitin-Proteasome Pathway Components in Aorta of Rats with Chronic Renal Failure Complicated with Atherosclerosis

目的:观察消瘀泄浊饮对慢性肾衰竭(CRF)动脉粥样硬化大鼠主动脉泛素-蛋白酶体通路(ubiquitin-proteasome pathway,UPP)组分的影响。方法:40只SD大鼠随机选取正常对照组10只,其余大鼠采用5/6肾切除同时予高脂饮食制作CRF动脉粥样硬化大鼠模型,造模10周后检测血肌酐(SCr)、尿素氮(BUN),造模成功的大鼠随机分为3组:模型组、阿托伐他汀(立普妥)组、消瘀泄浊饮组,每组10只;给药8周后再分别检测血SCr、BUN水平,免疫组化法检测主动脉基质金属蛋白酶-9(MMP-9)、泛素C(Ubc)、泛素接酶E2B(Ube2b)、蛋白酶体亚基A1蛋白(PsmA1)的表达,实时荧光定量PCR法检测主动脉Ubc、Ube2b、PsmA1mRNA表达量。结果:与模型组比较,消瘀泄浊饮组SCr、BUN显著降低(P<0.01),消瘀泄浊饮组主动脉MMP-9、Ubc、Ube2b、PsmA1蛋白以及Ubc、Ube2b、PsmA1mRNA的表达明显下降(P<0.05或P<0.01)。结论:消瘀泄浊饮可通过抑制活化的泛素-蛋白酶体通路而起到防治CRF大鼠动脉粥样硬化作用。

Objective:To investigate the effects of Xiaoyu Xiezhuo Decoction on Expressions of ubiquitin-proteasome pathway components in the aorta of rats with chronic renal failure complicated with atherosclerosis.Methods:10 rats were randomly selected from the 40 male SD rats as normal control group,the rest rats were established into CRF-MN by 5/6 nephrectomy and high fat diet.After 10 weeks,serum SCr,blood BUN were detected,rats successfully modeled were randomly divided into 3 groups:model group,Atorvastatin(Lipitor)and Xiaoyu Xiezhuo Decoction groups,each group contained 10 rats.After being treated for 8 weeks,SCr、BUN were detected,Immunohistochemistry was applied to determine the expressions of MMP-9,Ubc,Ube2b,PsmA1 in aorta tissue,Real-time fluorescence quantitative PCR method was applied to determine the mRNA of Ubc,Ube2b,PsmA1 in aorta.Results:Compared with model group,the levels of SCr,BUM in Xiaoyu Xiezhuo Decoction group decreased significantly(P<0.01),and the expressions of MMP-9,Ubc,Ube2b,PsmA1 protein and Ubc,Ube2b,PsmA1mRNA in aorta tissue also decreased significantly(P<0.05 or P<0.01).Conclusion:Xiaoyu Xiezhuo Decoction can prevent and treat atherosclerosis by inhibiting the activation of ubiquitin-proteasome pathway in CRF rats.