人参养荣汤对慢性肾衰竭大鼠骨骼肌萎缩的影响

Effect of Renshen Yangrong Decoction on Skeletal Muscle Atrophy in Chronic Renal Failure Malnutrition Rats

目的观察人参养荣汤对慢性肾衰竭(CRF)大鼠骨骼肌萎缩的作用及机制。方法采用5/6肾切除方法制作CRF大鼠模型,术后8周测血肌酐(SCr)、尿素氮(BUN)以判断模型成败。造模成功的大鼠随机分为模型组,人参养荣汤组和复方α酮酸片(KA)组,每组9只;另设对照组(n=10)。治疗12周后,全自动生化仪检测SCr、BUN、血清白蛋白(Alb);取胫骨前肌、腓肠肌,进行称重、固定、HE染色观察其病理学改变;Western Blot测Jagged1-Notch通路蛋白水平。结果与对照组比较,模型组大鼠4周后体重明显减轻(P<0.01),8周后模型组大鼠血清SCr、BUN水平升高(P<0.01),Alb水平降低(P<0.01);肌纤维横截面积减少(P<0.01),细胞核移位;大鼠骨骼肌Jagged1、Notch蛋白水平均下调(P<0.01)。与模型组比较,人参养荣汤组和KA组大鼠的体重增加(P<0.01),SCr、BUN水平降低(P<0.01),Alb水平升高(P<0.01);大鼠骨骼肌肌纤维横截面积增加(P<0.05);骨骼肌中Jagged1、Notch蛋白水平上调(P<0.05)。结论人参养荣汤与KA均可改善CRF大鼠营养不良,增加其体重,改善SCr、BUN和Alb,减轻骨骼肌萎缩,两者效果相当。人参养荣汤作用机制可能与调节Jagged1/Notch信号通路相关。

Objective To investigate the effect and mechanism of Renshen Yangrong Decoction on skeletal muscle atrophy in rats with chronic renal failure(CRF).Methods The rat model of CRF was established by 5/6 nephrectomy.Serum creatinine(SCr)and blood urea nitrogen(BUN)were measured after 8 weeks of operation to determine the success of the model.The successful model rats were randomly divided into model group,Renshen Yangrong Decoction group and Compoundα-Ketoacid Tablets(KA)group,9 rats in each group,and another sham operation group(10 rats)was established.After 12 weeks of treatment,SCr,BUN,serum albumin(Alb)were measured;tibialis anterior and gastrocnemius muscles were taken for weighing,fixation and HE staining to observe pathological changes;Western Blot was used to test the levels of Jagged1-Notch pathway proteins.Results Compared with the control group,the body weight of the model group was significantly decreased after 4 weeks(P<0.01).After 8 weeks,the levels of SCr and BUN in model rats were increased(P<0.01),and Alb level was decreased(P<0.01),the cross sectional area of muscle fibers were decreased(P<0.01),the levels of Jagged1 and Notch proteins in the model group were down-regulated(P<0.01).Compared with the model group,the body weight of the Renshen Yangrong Decoction group and the KA group were increased(P<0.01),the levels of SCr,BUN were decreased(P<0.01),meanwhile,the Alb level was increased(P<0.01),the skeletal muscle fiber cross sectional area were increased(P<0.05),the levels of Jagged1 and Notch protein in the skeletal muscle were up-regulated(P<0.05).Conclusions Renshen Yangrong Decoction could improve the body weight,increase the levels of SCr,BUN and Alb,and ameliorate skeletal muscle atrophy in CRF rats with malnutrition,with the efficacy similar to that of KA.The mechanism might be related to regulating Jagged1/Notch signaling pathway.