Authors

Da Sun*,#, Jia Chen**, Xiaoqing Yan***, Chi Zhang****, Haishan Tian***, Hao Ji*, Sue Lin*, Renyi Peng*, Libo Jin*

Departments

*Institute of Life Sciences, Wenzhou University, Wenzhou 325000, China - **Sichuan Provincial Center for Mental Health, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, China - ***School of Pharmaceutical Sciences at the Wenzhou Medical University, Wenzhou, China - ****The Third Affiliated Hospital of Wenzhou Medical University, Ruian, Wenzhou, China

Abstract

Objective: The objective is to explore the mechanism of Tripterygium wilfordii polyglycosides (TWP) in improving fibrosis in diabetic nephropathy by inhibiting the TGF-beta 1/NF-kappa B signalling pathway. 

Methods: Fifty clean SD rats were randomly selected, and 10 of them were in the normal control group. The remaining 40 rats were injected intravenously with streptozotocin to establish the model of type 2 diabetes mellitus. After successful modelling, the rats were randomly divided into a model group and low-, medium-, and high-dose TWP groups (1, 3, and 6 mg/kg/d), with 10 rats in each group. The normal control group and model group were given the same amount of distilled water by gavage. The TWP groups were given different doses of TWP by gavage, and the rats were sacrificed after 8 weeks of gavage. The changes in renal function, urinary microalbumin (UMA), and blood lipids in rats were detected using blood samples. The levels of serum TGF-beta 1 and NF-kappa Bp65 were detected using ELISA, and the levels of TGF-beta 1 and NF-kappa Bp65 were detected using Western blotting. 

Results: Compared with the control group, the levels of triglycerides and total cholesterol in the model groups were significantly higher (P<0.05), whereas the levels of high-density lipoprotein cholesterol were not significantly different (P>0.05). The levels of UMA in the model group were significantly higher than those in the control group (P<0.05), and the levels of UMA in the TWP rats in each dose group were significantly lower than those in the model group (P<0.05). The levels of UMA in the medium- and high-dose TWP groups were significantly lower than those in the low-dose group (P<0.05). The serum levels of TGF-beta 1 and NF-kappa Bp65 in the model group were significantly higher than those in the control group (P<0.05). After different doses of TWP treatment, the serum levels of TGF-beta 1 and NF-kappa Bp65 in the middle- and high-dose groups were significantly lower than those in the model group (P<0.05). Compared with the control group, the levels of TGF-beta 1 and NF-kappa Bp65 in the kidney tissue of the model group were significantly higher than those in the control group (P<0.05). Compared with the model group, the expression levels of TGF-beta 1 and NF-kappa Bp65 in the kidney tissue of rats in each dose group were significantly lower (P<0.05), and the expression levels of TGF-beta 1 and NF-kappa Bp65 in the middle- and high-dose TWP groups were significantly lower than those in low-dose group (P<0.05).

Conclusion: The TGF-beta 1/NF-kappa B signalling pathway mediates the occurrence and development of renal fibrosis. Tripterygium wilfordii polyglycosides can improve diabetic renal fibrosis by inhibiting the TGF-beta 1/NF-kappa B signalling pathway in a dose-dependent manner.

Keywords

Tripterygium wilfordii polyglycosides, TGF-β1/NF-κB signalling pathway, diabetic nephropathy, renal fibrosis.

DOI:

10.19193/0393-6384_2019_6_512