Skeletal muscle wasting in diabetic kidney disease rats and the effect of low-protein diet combined with a-keto acids / 中华肾脏病杂志

ABSTRACT

Objective To observe the muscle wasting in diabetic kidney disease (DKD) model of type 2 and non-obese diabetes mellitus in Goto-Kakizaki (GK) rats,and to evaluate the effect of lowprotein diet supplemented with α-keto acids on muscle wasting.Methods Forty-five male 24-weekage GK rats were randomly divided into three groups:normal protein diet group (22％ casein diet,NPD),low protein diet group (6％ casein diet,LPD) and LPD + α-keto group (5％ casein + 1％ α-keto,Keto).Fifteen gender-and age-matched Wistar rats were served as the control group (CTL).The living condition of GK rats was observed and body weight was measured once a week.Urine albumin,serum glucose,lipids,albumin,creatinine and urea nitrogen were measured at the age of 24,32,40,48 weeks.Soleus muscle at the age of 48-week was observed to calculate the muscle size with software.Expressions of atrogin-1,MuRF-1 and MyoD,myogenin were examined by Q-PCR and Western blotting.Results Compared with the CTL group,NPD,LPD,Keto groups had lower body weight [(317.90± 13.81),(330.38±11.96),(390.44±12.25) g vs (429.43± 16.85) g,all P ＜ 0.05],higher urine albumin [(14.36±5.52),(8.12±4.61),(5.58±3.50) mg/24 h vs (0.61±0.16) mg/24 h,all P ＜ 0.05],higher serum creatinine [(81.50±7.88),(66.32±8.36),(63.44±8.21) μmol/L vs (24.43±6.15) μmol/L,all P ＜0.05] and urea nitrogen [(7.53±1.05),(5.63±1.40),(5.54±0.97) mmol/L vs (2.98±0.62) mmol/L,all P ＜0.05].The cross-sectional area of soleus muscle fibers was larger in CTL group.Compared with CTL group,the expression levels of atrogin-1 and MuRF-1 increased significantly (all P ＜ 0.05),and of MyoD and myogenin decreased significantly in NPD,LPD,Keto groups (all P ＜ 0.05).In Keto group after 40 weeks,muscle wasting was improved compared with NPD and LPD group [body weight (381.62± 15.82) g vs (331.50±17.58),(326.60± 13.43) g,all P ＜ 0.05],cross-sectional area of soleus muscle increased,levels of urine albumin,serum creatinine and urea nitrogen decreased (all P ＜ 0.05),the protein expressions of atrogin-1 and MuRF-1 decreased,and myogenin and MyoD were higher as compared to CTL group (all P ＜ 0.05).There were no significant differences between NPD and LPD group.Conclusions In DKD condition,protein degradation in the skeletal muscle is accelerated,the genes which control muscle atrophy are activated,and proliferation and differentiation of the muscle satellite cells are impaired.Low-protein diet supplemented with α-keto acids can improve muscle wasting induced by DKD.