Manshenkangning Ameliorating Renal Interstitial Fibrosis Is Associated With TGF-β1/Smad3 Signaling Regulating MiR-21 And MiR-29

OBJECTIVE:To observe effects of Manshenkangning granules(MG) on the kidney tissue of UUO rats about the expression of TGF-β1, Smad3,mi R-21 and mi R-29.METHODS:60 male Wistar rats were randomly divided into 6 groups of equal size(n=10): Group 1(normal control group): control rats + placebo; Group 2(sham operation group): sham operation rats + placebo; Group 3(model group): UUO operation rats + placebo; Group 4(Valsartan group): UUO operation rats + Valsartan(8 mg·kg-1·d-1), Group 5(high dose MG group): UUO operation rats + high dose MG(30 mg·kg-1·d-1); Group 6(normal dose MG group): UUO operation rats + MG(15 mg·kg-1·d-1). Normal control group was received distilled water by gavages. 3 day before UUO operation, all the treatment groups were received medicine by gavages, and the normal control group rats, sham operation group rats and model group rats were received distilled water by gavages. The rats were sacrificed after 12 days of treatment, recorded weights and bilateral kidneys wet weight, blooded from aortaventralisfor the detection of CREA and BUN. Left kidneys of all the rats were taken for further analysis. Immunohistochemical staining of TGF-β1 and p-Smad3 was performed. RT-PCR was used to quantify TGF- β1, Smad3, Vimentin, mi R-21 and mi R-29.RESULTS:HE and Masson staining revealed that the degree of renal fibrosis was increased in the model group and decreased in all treatment groups as compared to the model group; compared with sham operation group, the CREA and BUN of model group were increased in different degree(P<0.01). However, compared with model group, results of treatment group were not statistically significant, but there is a downward trend; TGF-β1 and p-Smad3 protein expression was increased in the UUO operation rats(P<0.01) and significantly decreased by valsartan and high dose MG treatment.The expression of TGF-β1, Smad3,Vimentin m RNA and mi R-21, was increased in the model group(P<0.05) and significantly decreased in all treatmen groups(P<0.05). Expression of mi R-29 was decreased in the model group(P<0.05) and significantly increased in all treatmen groups(P<0.05).CONCLUSION:The obstructive nephropathy was attenuated by Manshenkangning granules. Thus the beneficial effect of Manshenkangning granules might be at least partially attributed to TGF-β1/Smad3 signal pathway regulating the mi R-21 and mi R-29.