消瘀泄浊饮对慢性肾衰竭营养不良大鼠骨骼肌组织UPP组分表达的影响

Effects of Xiaoyu Xiezhuo Decoction on Expression of Ubiquitin-Proteasome Components in Skeletal Muscle of Rats with Chronic Renal Failure and Malnutrition

目的:观察消瘀泄浊饮对慢性肾衰竭(chronic renal failure,CRF)营养不良大鼠骨骼肌组织泛素-蛋白酶体相关组分的影响。方法:46只SD雄性大鼠,随机选取正常组10只,其余大鼠采用5/6肾切除同时予以低蛋白饮食制作CRF营养不良大鼠模型,观察营养不良发生时间,随机分成模型组、复方ɑ-酮酸(开同)组、消瘀泄浊饮组,每组12只,治疗四周后检测血肌酐、尿素氮、白蛋白水平,用免疫组化法检测骨骼肌组织泛素C、泛素连接酶E2B、蛋白酶体亚基A1蛋白的表达,用实时荧光定量PCR法检测骨骼肌组织泛素C、泛素连接酶E2B、蛋白酶体亚基A1m RNA表达量。结果:CRF大鼠在术后10周出现营养不良,与模型组相比,消瘀泄浊饮治疗组大鼠血清白蛋白明显增加(P<0.01),营养状况和肾功能明显改善(P<0.01),消瘀泄浊饮组骨骼肌组织泛素C、泛素连接酶E2B、蛋白酶亚基A1蛋白以及m RNA的表达明显下降(P<0.05或P<0.01)。结论:消瘀泄浊饮可能通过下调骨骼肌组织泛素-蛋白酶体通路相关组分的表达,减少肌肉组织的降解,从而改善CRF营养不良。

Objective ： To observe the effect of Xiaoyu Xiezhuo Decoction on ubiquitin - proteasome components in skel- etal muscle of rats with chronic renal failure （CRF） and malnutrition（MN）. Methods：Ten rats were randomly selected out of 46 male SD rats as the normal group. The rest rats were established CRF - MN by 5/6 nephrectomy and low protein diet. The happening time of MN in them was recorded. Successful model rats were randomly divided into 3 groups： 12 rats in model group, 12 rats in control group treated with composite n -keto acid and 12 rats in Xiaoyu Xiezhuo Decoction group. After being treated for 4 weeks, serum creatinine（ Ser）, blood urea nitrogen （BUN） and albumin were detected. The immunohistoehemistry was applied to measure the expressions of ubiquitin C （ Ube ） , ubiquitin - conjugating enzyme （Ube2b） and proteasome subunit A1 （PsmA1） in skeletal muscle tissue. Real -time fluorescence quantitative PCR method was applied to measure the mRNA of Ubc, Ube2b and PsmAl in skeletal muscle tissue. Results： CRF rats re- vealed MN at the end of lOth week after modeling. Compared with the model group, the condition of MN and renal func- tion of Xiaoyu Xiezhuo Decoction group was significantly improved （ P 〈 0. 01 ）. Expressions of protein and mRNA of Ube ,Ube2b and PsmA1 in skeletal muscle tissue decreased significantly （P 〈 0. 01 or P 〈 0.05 ）. Conclusion： Xiaoyu Xiezhuo Decoction can improve the malnutrion condition of CRF rats, which is possible by way of inhibiting expressions of ubiquitin - proteasome pathway components so as 1o reduce the degradation of muscle tissue.