Study On The Protective Effect And Mechanism Of Berberine On Chronic Renal Failure Rats

Objective:In a rat model of chronic renal failure（CRF）caused by5/6 nephrectomy,the effects of berberine（BBR）on renal function,some extracellular matrix proteins,inflammation-related factors,matrix metalloproteinases（MMPs）,renal The effect of BBR on renal function,some extracellular matrix proteins,inflammation-related factors,matrix metalloproteinases（MMPs）,histomorphological changes and molecules involved in the TGF-β₁/ERK1/2 signalling pathway.The study of the mechanism of action of BBR in reducing renal fibrosis and delaying CRF will provide an objective experimental basis for the clinical application of BBR in the treatment of CRF and guide the clinical use of this drug.Methods:Forty SPF-rated male SD rats were randomly divided into a sham-operated（Sham）group,a renal failure model group,a berberine treated（BBR）group,and a Uremic clearance granules（UCG）group.All groups except the sham-operated group underwent 5/6 nephrectomy to simulate renal failure.The BBR group was given 300 mg/kg of BBR by gavage and the pellet group was given 2.2 g/kg of urotoxin solution.After8 weeks of continuous administration,the rats were executed and fasting blood and kidney tissues were collected.Blood urea nitrogen（Bun）,serum creatinine concentration（Scr）and MMP-2 and MMP-9 were measured by the kit.Protein immunoblotting was used to detect the expression levels of FN,Col-I,Col-III,α-SMA,TGF-β1 and p-ERK1/2proteins.Renal histopathological sections were stained with PAS and Masson stain to observe the extent of fibrosis in renal tissue.Results:Compared with the Sham group,the levels of Scr and Bun in the Model group were significantly higher,and the difference was statistically significant（P<0.05）.Compared with the Model group,the pathological changes such as edema and inflammatory cell infiltration of renal tubular epithelial cells were reduced in the BBR group and collagen deposition was less than before,suggesting that the kidney was less damaged.Compared with the Model group,the protein expression levels of FN,α-SMA,Collagen-I,Collagen-III,TGF-β1 and p-ERK1/2 were decreased in the BBR and uremic clear groups,and the difference was statistically significant（P<0.05）.Conclusion:BBR has a protective effect on CRF.BBR can significantly improve the renal function of CRF.The mechanism may be that BBR reduces the production of ECM and reduces the inflammatory response by inhibiting the TGF-β1/ERK1/2 pathway;at the same time,it increases the level of MMP-2 and MMP-9 to promote the degradation of ECM and reduce RIF,thus playing a certain protective effect on CRF.