Mitochondrial damage in proetin-energy wasting of skeletal muscle in rats with diabetic kidney disease and the effect of low-protein diet combined with α-keto acids
10.3760/cma.j.issn.1001-7097.2013.11.006
- VernacularTitle:糖尿病肾病大鼠骨骼肌蛋白能量消耗相关线粒体损伤及低蛋白联合α酮酸的作用
- Author:
Jialin WANG
;
Weijie YUAN
;
Lijie GU
;
Juan HUANG
;
Ting DONG
- Publication Type:Journal Article
- Keywords:
Diabetic nephropathies;
Muscle,skeletal;
Energy metabolism;
Mitochondrion;
Diet,protein-restricted
- From:
Chinese Journal of Nephrology
2013;29(11):824-829
- CountryChina
- Language:Chinese
-
Abstract:
Objective To observe the mitochondrial damage associated with protein-energy wasting of skeletal muscle in diabetic kidney disease (DKD) model of Goto-Kakizaki(GK) rats and evaluate the effects of low-protein diet supplemented with α-keto acids on muscle wasting.Methods Forty-five male 24-week-age GK rats were randomly divided into three groups,normal protein diet group (NPD),low-protein diet group (LPD) and LPD +or-keto group (Keto).Fifteen gender and age matched Wistar rats were served as control group (CTL).The living condition of GK rats was observed and the weight was measured once a week.Urine albumin,serum glucose,creatinine and urea nitrogen were measured at 24,32,40,48 week age.Soleus muscle was observed to calculate the muscle size and the percentage of Ⅰ and Ⅱ type muscle fiber with software after SDH and NADH staining at 48-week-age.Tissue ultrastructure was observed under the transmission electron microscopy.The activity of citrate synthase was detected by spectrophotometer.Expression of mitochondrial DNA was examined by Q-PCR.Results Compared with the CTL group,NPD,LPD and Keto groups had lower body weight,higher urine albumin,higher serum creatinine and urea nitrogen (P ＜ 0.05).The crosssectional area of muscle fibers was larger in CTL group.Compared with CTL group,the muscle fiber was partly broken,the mitochondrial morphology was obviously changed,the percentage of type Ⅱmuscle fiber was increased significantly (P ＜ 0.05),and the activity of citrate synthase and the number of mitochondrial DNA were decreased significantly in NPD,LPD and Keto groups (P ＜ 0.05).In Keto group,muscle wasting was improved compared with NPD and LPD group (P ＜ 0.05),the crosssectional area of soleus muscle increased and the percentage of type Ⅱ muscle fiber decreased,levels of urine albumin,semm creatinine and urea nitrogen decreased (P ＜ 0.05).Under transmission electron microscopy,the muscle fiber of keto group was intact and mitochondiral morphology was close to that of CTL group.The activity of citrate synthase and number of mitochondiral DNA were higher as compared to CTL group (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,mitochondrion is swelling,the number of mitochondrial DNA is decreased and mitochondrial function is impaired.Low-protein diet supplemented with α-keto acids can improve mitochondrial damage and muscle wasting induced by DKD.
