基于分子对接技术的藤茶总黄酮对高尿酸血症肾功能损伤保护机制研究

目的 探讨藤茶总黄酮(total flavonoids from Ampelopsis grossedentata,AGTF)对高尿酸血症(hyperuricemia,HUA)肾功能损伤的保护机制.方法 利用分子对接技术,将藤茶总黄酮主要活性成分与HUA相关靶点蛋白尿酸重吸收转运体1(uric acid reabsor...

Protective effect and mechanism of total flavonoids from Ampelopsis grossedentata on renal function injury of hyperuricemia based on molecular docking technology

Objective To explore the protective mechanism of the total flavonoids from Ampelopsis grossedentata(AGTF) on renal function injury of hyperuricemia(HUA). Methods Main active components of AGTF were connected with HUA related target proteins uric acid reabsorption transporter 1(URAT1), glucose transporter 9(GLUT9), adenosine triphosphate binding cassette transporter G2(ABCG2), xanthine oxidase(XOD), and adenosine deaminase(ADA) by using molecular docking technology. Renal injury rats model of HUA was prepared by adenine combined with ethambutol, and AGTF was used for intervention. Activities of urate metabolizing enzyme such as XOD and ADA, levels of uric acid, renal function biochemical indicators such as creatinine and urea nitrogen in serum were detected. Hematoxylin-eosin(HE) staining was used to observe the pathological changes of rat kidney. Expressions of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6), and transforming growth factor-β(TGF-β) in renal tissues were determined by Western blotting. Expression of URAT1, GLUT9, and ABCG2 were detected by immunohistochemistry. Results Molecular docking results showed that the main components of AGTF of dihydromyricetin, myricetin, quercetin, and grossedentatasin all had higher docking scores with disease-related targets, suggesting that AGTF may prevent and treat HUA renal function injury by acting on URAT1, GLUT9, ABCG2, ADA and XOD. AGTF significantly reduced the activities of XOD and ADA, levels of uric acid, creatinine and urea nitrogen in serum of HUA renal injury rats(P < 0.05, 0.01). AGTF alleviated the thickening of glomerular basement membrane in model rats, reduced the disorder and necrosis of renal tubular arrangement, and inhibited the proliferation of fibrous tissue in lesion area. Western blotting and immunohistochemistry results showed that AGTF significantly reduced the expressions of inflammatory factors such as TNF-α, IL-1β, IL-6, TGF-β, and urate reabsorption related proteins such as URAT1 and GLUT9(P < 0.05, 0.01), significantly increased the expression of urate excretion related protein such as ABCG2 in renal tissue(P < 0.05, 0.01). Conclusion AGTF has a good protective effect on renal function injury of HUA. AGTF could inhibit the expressions of TNF-α, IL-1β, IL-6, and TGF-β to alleviate inflammatory pathway reactions, and regulate the expressions of urate transporter related proteins such as URAT1, GLUT9, and ABCG2 to promote metabolism of uric acid, which are consistence with predicted results of molecular docking.