Effect of Modifie Drehmanniae Prescription on TGF-β1-CTGF Signaling Pathway to Improve Renal Interstitial Fibrosis

OBJECTIVE To study the effect of modified Rehmannia Recipe on renal interstitial fibrosis in rats with partial ureteral obstruction (PUUO) and to explore its possible mechanism. METHODS Eighty SD rats were randomly divided into control group， model group， low dose group and high dose group ( n =20). In the model group， the model of PUUO was established by lumbar large muscle tube embedding method. Only the left kidney was removed in the control group.High dose group (2 mL/d) and low dose group (1 mL/d) were treated with Modified rehmannia decoction， the control group and the model group were given the same amount of normal saline. The levels of serum creatinine (SCr)， urea nitrogen (BUN) and 24 h urinary protein were determined in each group. Blood samples were collected from each group at 4th week and 8th week after modeling. Measurement of renal tissue size， renal cortical thickness. The renal histopathological changes were observed by staining with HE and Masson， and the renal fibrosis was observed. The expressions of transforming growth factor-β1 (TGF-β1)， connective tissue growth factor (CTGF) and α-smooth muscle actin (α-SMA) in renal tissue were detected by immunohistochemistry. The expression of TGF-β1 and CTGF mRNA was detected by qPCR. RESULTS At 4th week， inflammatory cell infiltration， local focal necrosis and necrosis were observed in the model group， and more collagen fibrosis was formed. Compared with the model group， the pathological changes of the high and low dose group were not obvious， and only a small interstitial fibrosis was widened. After 8 weeks: model group lymphocyte infiltration， glomerular necrosis， the structure completely changed. Interstitial fibrous hyperplasia. In the high and low dose group， the infiltration of inflammatory cells was lighter than that of the model group， the staining of the collagen was lighter and the high dose group had the smallest change. The average positive expression rate of TGF-β1， CTGF and α-SMA protein was not significantly different between the two groups at 4th week compared with the model group. At the 8th week， the two drug treatment groups had Significant difference ( P <0.01). Comparison of TGF-β1， CTGF mRNA expression was found when the low-dose group 4 weeks with model group had no differences as compared to high dose group and the model group were different ( P <0.05) as compared to 8th week. CONCLUSION Modified rhubarb may reduce the expression of TGF-β1-CTGF and down-regulate the expression of α-SMA， reduce the pathological changes of renal fibrosis and delay the development of renal fibrosis.