Study on the improvement of Compound danshen tablets on blood lipid levels and the mechanism of protecting renal functions in hyperlipidemia model rats / 中国药房

ABSTRACT

OBJECTIVE To investigate the effect of Compound danshen tablet s o n improving the blood lipid levels and the mechanism of protecting renal functions in hyperlipidemia model rats. METHODS Sixty male SD rats were divided into normal group，model group ，simvastatin combined with （2S）-N-[N-（3，5-difluorophenylacetyl）-L-alanyl]-2-phenylglycine tert butyl （DAPT）group and low-dose ，medium-dose and high-dose groups of Compound danshen tablets ，with 10 rats in each group. Rats in the normal group received routine diet. The other 5 groups were intraperitoneally injected with 75％ yolk emulsion 10 mL/kg， fasting and drinking freely. After 16 h，they were fed high-fat diet for 4 weeks. Simvastatin combined with DAPT group was given simvastatin 0.002 g/kg and DAPT 0.012 g/kg at the same time of modeling. The low-dose ，medium-dose and high-dose groups of Compound danshen tablets were given Compound danshen tablets 0.25，0.5 and 1 g/kg respectively at the same time of modeling ， the normal group and model group were given equal volume of distilled water ，once a day ，for 4 weeks. The serum levels of total cholesterol（TC），triglyceride（TG），creatinine（Cr）and urea nitrogen （BUN）in serum were detected by biochemical method ； kidney coefficient of rats was calculated ；histopathological changes of rat kidney were observed by HE staining ，and the renal injury was scored according to the degree of renal tubular injury and glomerular sclerosis in renal cortex ；expression levels of Notch signal receptor 1（Notch 1），Notch signal ligand 1（Jagged1）and hairy division associated enhancer 1（Hes1）in kidney were detected by immunohistochemistry ；mRNA expressions of Notch 1，Jagged1 and Hes 1 in renal tissue were detected by real-time fluorescence quantitative polymerase chain reaction. RESULTS Compared with normal group ，the serum levels of TG ， TC，Cr and BUN were increased significantly in model group （P＜0.05）；renal coefficient increased significantly （P＜0.05）； pathological changes occurred in renal tissue ，and the scores of renal tubular injury and glomerular sclerosis increased significantly （P＜0.05）；protein and mRNA expressions of Notch1， Jagged1， Hes1 in renal tissue were increased significantly（P＜0.05）. Compared with model group ，serum levels of TG ，TC，Cr and BUN ，renal coefficient ，the scores of renal tubular injury and glomerular sclerosis ，protein and mRNA expression of Notch 1，Jagged1 and Hes 1 in renal tissue were all decreased in low-dose ，medium-dose and high-dose groups of Compound danshen tablets （P＜0.05），and most indexes showed a dose-dependent trend ；the degree of renal lesions was reduced. CONCLUSIONS Compound danshen tablets possess obvious hypolipidemic effect ，and can protect the renal function of hyperlipidemia model rats by down-regulating Notch 1/Jagged1 signal pathway.