The Effect Of Rhynchophylline On Renal Fibrosis In Spontaneous Hypertensive Rats

Objective: To observe the effect of Rhy on renal fibrosis in spontaneous hypertensive rats?SHR?and its possible mechanism.Methods: Thirty-two SHR were randomly divided into rhynchophylline high and low dose groups?10?2.5mg·kg-1·d-1,n=8?,captopril positive control group?17.5 mg·kg-1·d-1,n=8?,SHR model group?distilled water 5ml·kg-1·d-1,n=8?.Eight male WKY rats?distilled water 5ml·kg-1·d-1,n=8?were used as control.After 1 week adaptive feeding,rats in treatment groups were given these dosages daily for 10 weeks.Blood pressure was measured using noninvasive tail arterial blood pressure analysis system.Body weight,left kidney and right kidney were weighed and kidney weight index was calculated respectively.The primary pathologic changes and collagen deposition of kidney were observed by hematoxylin and eosin stain?HE?or Masson staining.Levels of serum creatinine?Scr??blood urea nitrogen?BUN??nitric oxide?NO??hydroxyproline?HYP??superoxide dismutase?SOD??malondialdehyde?MDA?were measured by reagent kits.The content of tumor necrosis factor-??TNF-??was detected by ELISA.The expressions of TGF-?₁ positive cells in kidney was measured by immunohistochemistry.The expressions of TGF-?₁?Smad3?Smad7?iNOS?MMP-9 and TIMP-l proteins in kidney were detected by Western blot.Results:?1?Compared with WKY,SBP of model group was significantly increased?P<0.01?;after 10 weeks feeding,SBP of groups treated with high and low dose of rhynchophylline significantly decreased?P<0.01?.?2?The kidney weight index was increased in SHR,and those in all drug-treated groups were lower than SHR?P >0.05?.?3?Compared with WKY,the level of Scr ? BUN in model group were markedly increased?P<0.01?;after 10 weeks feeding,each doses group was significantly decreased?P<0.05 or P<0.01?.?4?Messangial matrix cells and basement membrane of glomerular were proliferated,and collagen deposition was appeared in the renal interstitium in SHR,while rhynchophylline could ameliorate these pathological damages.?5?Compared with WKY,the content of HYP?NO?MDA and TNF-? in model group were significantly increased?P<0.01?,SOD were obviously decreased?P<0.01?;compared with the model group,rhynchophylline could markedly decrease the level of HYP ? NO ? MDA ? TNF-? and increase the level of SOD?P<0.05 or P<0.01?.?6?Compared with WKY,the expressions of TGF-?₁,Smad3,iNOS,MMP-9,TIMP-1proteins in kidney were significantly increased in SHR,the expression of Smad7 was appeared with lower content?P<0.01?.Supplementation with rhynchophylline markedly down-regulated protein expression of TGF-?₁,Smad3,iNOS,CTGF,MMP-9,TIMP-1and up-regulated the expression of Smad7?P<0.05 or P<0.01?.Conclusion: Rhynchophylline can significantly reduce blood pressure and improve renal fibrosis of SHR.Its mechanisms may be related with regulating TGF-?₁ and its downstream signaling pathways,restoring the MMP-9/TIMP-1 balance,inhibiting oxidative stress,reducing the content of TNF-?.