Improvement Effects of Water Extract of Astragalus membranaceus on Chronic Renal Failure Model Rats and Its Effects on MAPK Signaling Pathway / 中国药房

ABSTRACT

OBJECTIVE： To investigate the improvement effects of water extract of Astragalus membranaceus on chronic renal failure （CRF） model rats and its effects on MAPK signaling pathway， and to investigate possible mechanism. METHODS： Male SD rats were randomly divided into control group （10 rats） and model group （50 rats）. CRF model was established by intragastric administration of 25％ Adenine suspension 200 mg/kg （once a day， for consecutive 28 d）. After modeling， modeling group was randomly divided into model group， benazepril group （positive control， 2 mg/kg）， A. membranaceus water extract low-dose， medium-dose and high-dose groups （1.5， 3， 6 g/kg，by crude drug）， with 10 rats in each group. Control group and model group were given constant volume of normal saline intragastrically， and administration groups were given relevant medicine intragastrically， once a day， for consecutive 28 d. Twelve hours after last medication， the contents of serum renal function indexes （serum creatinine， urea nitrogen， uric acid） were determined by colorimetry. ELISA method was used to detect the levels of serum inflammatory factors （IL-1β， IL-6 and TNF-α）. The activity or content of oxidative stress related indexes （SOD， CAT and MDA）in renal tissue of rats were determined by hydroxylamine method， visible spectrophotometry method and thiobarbituric acid method. The mRNA expression of apoptosis-related factors （Bax， Bcl-2， Caspase-3） in renal tissue， MAPK signaling pathway-related regulatory protein p38 MAPK， phosphorylated p38 MAPK（p-p38 MAPK）， ERK1/2， phosphorylated ERK1/2 （p-ERK1/2）， JNK and phosphorylated JNK （p-JNK） were determined by real- time PCR and Western blotting assay. RESULTS： Compared with control group， the contents of renal function indexes and the levels of inflammatory factors in serum， MDA content， mRNA expression ratio of Bax and Bcl-2 （Bax/Bcl-2）， mRNA related expression of Caspase-3， related expression of phosphorylation product of MAPK signaling pathway-related regulatory proteins （p-p38 MAPK， p-JNK， p-ERK1/2） in renal tissue were increased significantly in model group， while the activities of SOD and CAT were decreased significantly in renal tissue （P＜0.01）. Compared with model group， the contents of renal function indexes and the levels of inflammatory factors in serum， Bax/Bcl-2， related expression of phosphorylation product of MAPK signaling pathway-related regulatory proteins in renal tissue were decreased significantly in administration groups as well as MDA content and mRNA related expression of Caspase-3 were decreased significantly in benazepril group and A. membranaceus water extract medium-dose and high-dose groups； the activities of SOD and CAT in renal tissue were increased significantly in benazepril group and A. membranaceus water extract medium-dose and high-dose groups （P＜0.05 or P＜0.01）. MDA content and Bax/Bcl-2 of benazepril group were significantly lower than those of A. membranaceus water extract high-dose group （P＜0.05）. CONCLUSIONS： A. membranaceus water extract has a certain improvement effect on CRF model rats， and inhibit its inflammatory reaction， oxidant stress and cell apoptosis， the mechanism of which may be associated with inhibiting the expression of MAPK signaling pathway-related regulatory proteins.