Molecular Mechanism Of Multi-glycoside Of Tripterygium Wilfordii Hook.f. Delaying Progression Of Glomerularsclerosis In Chronic Kidney Disease

Molecular Mechanism of Multi-glycoside of Tripterygium wilfordii Hook.f. Delaying Progression of Glomerularsclerosis in Chronic Kidney Disease【Background/Aims】In this article, the first, we reviewed the progression in the treatment of chronic kidney disease (CKD) with pharmaceutical Tripterygium wilfordii Hook. f.(TWHF). The clinical trials of multi-glycoside of Tripterygium wilfordii Hookf.(GTW) in pharmacodynamics are mainly about proliferative glomerulonephritis, lupus nephritis and other primary and secondum CKD.It could improve some clinical symptoms such as proteinuria, hematuria and so on. The pharmacological effects of GTW and its bioactive component Triptolide (T4) include antiinflammatory,immunosuppression, protection of renal epithelial cell, etc.And it is also beneficial to restrain organ transplant rejection. The second, we discussed the pathomechanism of glomerularsclerosis in CKD and the effect of Chinese herbal medicine. The fundamental pathomechanisms and common pathway of the progression of CKD to end stage of renal disease is glomerularsclerosis, which relate with many harmful factors such as podocyte injury, mesangial proliferation, glomerular capillary reconstruction disorder. Regulating the expression of transforming growth factor (TGF)-βof glomerulus through TGF-β/Smad signaling pathway is critical to ameliorating the mesangial proliferation. The clinical trials in recent 30 years suggest that single or complex Chinese herbal medicine could delay the progression of glomerulosclerosis by ameliorating the harmful factors of glomerulosclerosis.The third, as a focal point in this article, it is reported that the effect of GTW on TGF-β/Smad signaling pathway in glomerularsclerosis model induced by adriamycin(ADR). For many years, GTW is widely used for the treatment in several types of glomerular disease in China. Our previous studies documented that GTW could ameliorate glomerularsclerosis by decreasing extracellular matrix(ECM) deposition through inhibiting the expression of TGF-β. However, there have been no studies on the effect of GTW on the regulation system of TGF-β signaling transduction——TGF-β/Smad signaling pathway. The aim of this study is to explore the potential molecular mechanisms of GTW ameliorating glomerularsclerosis by regulating TGF-β/Smad signaling pathway in ADR-induced nephropathy (ADRN)model.【Methods】In third part of this article, ADRN model was induced by extirpating the right kidney of rats and intravenous injection of ADR twice at a 4 weeks-interval. Daily oral administration of GTW (50mg/kg)and vehicle as a control was started after the model was established. Fifteen female Sprague-Dawley(SD) rats were randomly subdivided into sham-operated group, vehicle treated group and GTW treated group, and sacrified at the end of tenth week after operation. Proteinuria was determined at the end of weeks 2,4,8 and 10.From blood and kidneys taken at sacrifice, blood biochemical parameters, glomerular morphological changes, mesangial ultrastructure, a-smooth muscle actin (α-SMA) and collagen typeⅠwere examined. The mRNA expression of TGF-β1,Smad3,Smad7 and protein expression of TGF-β1,p-Smad2/3 were detected by RT-PCR and Western blotting respectively.【Results】GTW treatment ameliorated proteinuria and serum albumin significantly, but there were no effects on blood urea nitrogen(BUN),serum creatinine(Scr) and hepatic function. Mesangial cell(MC) proliferation, ECM and collagen deposition, the fluorescein stain of a-SMA and collagen typeⅠwere attenuated. Besides, GTW downregulated the mRNA expressions of TGF-β1,Smad3 and protein expression of TGF-β1, p-Smad2/3.Inversely, Smad7 mRNA was upregulated.【Conclusion】GTW could ameliorate glomerularsclerosis through inhibiting the activation of TGF-β1/Smad signaling pathway by regulating the mRNA or protein expression of TGF-β1,Smad3,p-Smad2/3 and Smad7.