| Objective: To observe the expression of Smad7 in tubulointerstitial fibrosis rats and the role of the Shen Luo Tong and its mechanism in tubulointerstitial fibrosis.Renal interstitial fibrosis is the common pathological procedure to renal function failure in many kinds of renal diseases. Renal interstitial fibrosis is characterized by atrophy of tubule,proliferation of myofibroblast(Myof) ,accumulation and deposition of extracecullular matrix (ECM). Transforming growth factor-β1 is one of the most important factor in renal fibrosis. It plays the key role in the progression of renal interstitial fibrosis. Smads protein family is a new cluster of proteins which mediates intracellular signal transduction of TGF-β. They translate signals from the cell surface to the nucleus where they down-regulate the expression of TGF-β. Smad7 is a specific endogenous inhibitor of TGF-βand induced by TGF-β.It plays negative feedback regulation role in TGF-βsignal transduction. So it can inhibit cell proliferation and reduce the desposition of ECM in obstructive kidney, prolong the processes of fibrotic.Shen Luo Tong is a basic formula for chronic nephropathy, animal experiments showed that it can alleviate the lesion of renal tissue and reduce the deposition of ECM in obstructive kidney, prolong the process of fibrosis ,but there is no evidence to confirm the role on smad7 for its mechanism .The study was to investigate the effect of Shen Luo Tong and Valsartan (a drug of ARB) in rats with unilateral ureteral obstruction (UUO).The renal morphology, transforming growth factor-β, Collagen III were examined.Method: Fourty female Sprague-Dawley rats were randomly divided into four groups (n=10), Shame-operation (SHAM), model (UUO), Shen Luo Tong (UUOS) and Valsartan (UUOV).Each animal was ligated left ureter except SHAM group. Drugs were administered from the day before operation but the saline were used in SHAM and UUO groups by oral. Animals were sacrificed after 14 days, the 24-hour urine and the blood were collected to test BUN Scr and 24-hour urinary protein.The left kidneys were harvested for pathological study. Immunohistochemistry staining and in situ hybridization were used for expression of TGFβ1,Col lll,Smad 7.Result:①Scr and BUN in UUO group was higher than SHAM group markedly and were lowered in treated group(P<0.05). But there in no differences in treated groups. (P> 0.05).②pathology: The renal tissues were stained with HE and Masson. There was no change in SHAM group. But in UUO group, interstitial macrophage and monocyte infiltration, renal tubular artrophy, emphraxis or expand were shown. The renal capsule adhere or expanded. Fibrous tissues proliferated around the renal capsule. The lesions in treated groups were slighter than in UUO group. It means that Shen Luo Tong and Vslsartan can inhibit fibrosis in obstructive nephropathy.③The expression of Col lll with Immunohistochemistry has shown a weak expression for Col lll in SHAM group, while in other groups the expression of Col lll increased markedly. Compared with the SHAM group, the expression of Col lll in UUO group was up-regulated markedly(P<0.05).Compared with the UUO group ,the expression of Col lll in UUOS,UUOV groups were down-regulated markedly(p<0.05). It means that Shen Luo Tong and Valsartan can inhibit the expression of Col lll in obstructive kidney. But there in no differences in treated groups(P> 0.05).④The expression of TGFβ1 with immunohistochemistry and in suit hybridization showed that a weak expression of TGFβ1 in SHAM group ,while in other groups the expression of TGFβ1 in protein level and its mRNA up-regulated markedly. They can be seen in renal tubular epithelial cell, interstitial cells. The expression of TGFβ1 in protein and its mRNA in UUO group was higher than that in SHAM group (p<0.05);Compared with the UUO group, TGFβ1 in UUOS,UUOV groups inhibited markedly(P<0.05). It means that Shen Luo Tong and Valsartan can inhibit the expression of TGFβ1 in protein and mRNA level in obstructive kidney.⑤The expression of Smad7mRNA with Immunohistochemistry and in suit hybridization: It has shown a stronger expression of Smad7mRNA in SHAM group, they can be seen in renal tubular epithelia cell, compared with SHAM group ,the expression of Smad7mRNA in other groups were down-regulated(P<0.05) .Compared with the UUO group ,the expression of Smad7 in UUOS group increased markedly (p<0.05), it means that Shen Luo Tong can up-regulate the expression of Smad7mRNA in obstructive kidney.Conclusion:①Shen Luo Tong can alleviate the lesion of renal tissue and reduce the desposition of ECM in obstructive kidney, prolong the processes of fibrotic.②Shen Luo Tong has the role to inhibit expression of TGFβ1 in protein and mRNA in obstructive kidney, and reduce synthesis of ECM.③Shen Luo Tong can up-regulate the expression of Smad7 and Smad7mRNA in obstructive kidney, and inhibit the tubulointerstitial fibrosis.
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