Study on the Improvement Effects of Sijunzi Decoction on Chronic Kidney Disease-protein Energy Wasting Model Mice and Its Mecranism / 中国药房

ABSTRACT

OBJECTIVE：To study the improvement effects of Sijunzi decoction on skeletal muscle atrophy in chronic kidney disease-protein energy wasting （CKD-PEW）model mice ，and to explore its potential mechanism . METHODS ：A total of 80 mice were randomly divided into sham operation group （n＝10）and modeling group （n＝70）. CKD-PEW model was established by removing 5/6 kidneys and giving a low-protein diet （4％ casein）for mice in modeling group. Totally 50 modeled mice were randomly divided into model group ，Sijunzi decoction low-dose ，medium-dose and high-dose groups [ 2.34，4.68，9.36 g/（kg·d）， by crude drug] ，Compound α-ketoacid tablets group [positive control ，1 g/（kg·d）]，with 10 mice in each group. Administration groups were given relevant medicine intragastrically ；sham operation group and model group were given constant volume of normal saline intragastrically ，once a day ，for consecutive 14 d. After last medication ，body weight of mice and wet mass of left tibialis anterior muscle （TA）were weighed ；TA cross-sectional area was determined ；protein synthesis and decomposition metabolism ability of TA were detected ；mRNA expressions of Bcl-2，Bax and Caspase-3 in TA were detected by Real-time PCR ；protein expressions of muscular dystrophin Fbox- 1 （Atrogin-1），myofloin-1 （MuRF-1），Rho-related protein kinase 1 （ROCK1）， phosphorylated PTEN （p-PTEN），phosphatidylinositol-3-kinase（PI3K）and phosphorylated Akt （p-Akt）in TA were detected by Western blotting. RESULTS ：Compared with the sham operation group ，the body weight ，TA wet weight ，protein synthesis metabolism ability of TA as well as protein expressions of PI 3K and p-Akt were decreased significantly in model group （P＜0.05）； the cross-sectional area of TA decreased significantly （P＜0.05）；protein decomposition metabolism ability of TA ，Bax/Bcl-2 ratio， Caspase-3 mRNA expression ，protein expressions of Atrogin- 1，MuRF-1，ROCK1 and p-PTEN were increased significantly （P＜ 0.05）. Compared with model group ，above indexes of mice were all improved significantly in Sijunzi decoction medium-dose ， high-dose groups and Compound α-ketoacid tablets group （P＜0.05）. CONCLUSIONS ：Sijunzi decoction can increase the body weight of CKD-PEW model mice and alleviate the skeletal atrophy ；the mechanism may be related to regulating ROCK 1/PTEN/Akt signaling pathway activity ，inhibiting the expression of Atrogin- 1 and MuRF- 1.