藤茶总黄酮抗高尿酸血症及肾功能保护作用研究

Protective Effect of Total Flavonoids from Ampelopsis Grossedentata on Renal Function and Anti-hyperuricemia Effect

目的:探讨藤茶总黄酮(AGTF)抗高尿酸血症及肾功能保护作用,为民族药食资源藤茶的进一步保健开发提供科学参考。方法:分别建立酵母、次黄嘌呤及氧嗪酸钾盐诱导的三种小鼠高尿酸血症动物模型,检测藤茶总黄酮0.125、0.25、0.5 g/kg对小鼠尿酸代谢指标血清尿酸(UA)、黄嘌呤氧化酶(XOD)和腺苷脱氨酶(ADA)含量的影响。采用腺嘌呤100 mg/kg和乙胺丁醇250 mg/kg复合诱导小鼠高尿酸血症肾功能损伤模型,分别检测其对小鼠血清中UA、XOD和ADA及肾功能指标肌酐(Cr)及尿素氮(BUN)含量,氧化损伤指标丙二醛(MDA)、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)含量/活性的影响;以及对肾脏组织相关炎症因子肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)及转化生长因子-β(TGF-β)含量的影响;并进行肾脏组织病理检察。结果:与正常对照组比较,三种高尿酸血症模型对照组小鼠血清UA、XOD及ADA的含量显著增高(P<0.01)。与模型对照组比较,藤茶总黄酮0.125、0.25、0.5 g/kg组能明显或部分降低UA、XOD及ADA的含量/活性(P<0.05或P<0.01)。与正常对照组比较,小鼠高尿酸血症肾功能损伤模型对照组血清UA、XOD、ADA、Cr、BUN及MDA含量明显升高,SOD和GSH-Px的活性明显降低以及肾脏组织中TNF-α、IL-1β及TGF-β水平明显升高(P<0.05或P<0.01)。与模型对照组比较,藤茶总黄酮0.125、0.25、0.5 g/kg组能明显或部分降低血清中UA、XOD、ADA、Cr、BUN及MDA的含量,升高SOD和GSH-Px的活性,降低肾脏组织TNF-α、IL-1β及TGF-β的含量(P<0.05或P<0.01)。病理苏木素-伊红染色(HE)检察提示,藤茶总黄酮0.25、0.5 g/kg组能明显改善模型小鼠基底膜增厚、局部间质炎细胞浸润,以及病变区域间质内纤维组织增生等病理变化。结论:藤茶总黄酮具有较好的抗高尿酸血症及肾功能保护作用,其机制可能与药物抗氧化应激损伤、抑制相关炎症途径反应有关。

Objective: To investigate the effect of total flavonoids from Ampelopsis grossedentata(AGTF) on hyperuricemia and renal function protection, and to provide the scientific reference for further development of health products from Ampelopsis grossedentata known as medical and food dual-purpose ethnic medicine. Methods:Three hyperuricemia animal mice models induced by yeast, hypoxanthine, and potassium oxazine were established respectively. The levels of serum uric acid(UA), xanthine oxidase(XOD) and adenosine deaminase(ADA) were detected after administration of 0.125 g/kg、0.25 g/kg and 0.5 g/kg AGTF. Adenine(100 mg/kg) combined with ethambutol(250 mg/kg) was used to establish a mice model of hyperuricemia renal function injury. The serum contents of UA, XOD, ADA, renal index creatinine(Cr) and the content of urea nitrogen(BUN) were detected, the contents/activities of oxidative damage indicators malondialdehyde(MDA), superoxide dismutase(SOD) and glutathione peroxidase(GSH-Px) were also detected. The contents of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β) and transforming growth factor-β(TGF-β) in renal tissues were detected, and the pathological examination of kidney tissue was performed. Results:Compared with the control group, the serum contents of UA, XOD and ADA were significantly increased in the model group(P<0.01). Compared with the model group, the contents/activities of UA, XOD and ADA in AGTF groups(0.125, 0.25,0.5 g/kg) were significantly or partially reduced(P<0.05 or P<0.01). Compared with the control group, the serum contents of UA, XOD, ADA, Cr, BUN and MDA were significantly increased in the model group. The contents of SOD and GSH-Px were significantly reduced, while the levels of TNF-α, IL-1β and TGF-β were significantly increased in kidney tissues(P<0.05 or P<0.01). Compared with the model group, the contents/activities of UA, XOD, ADA, Cr, BUN and MDA in AGTF groups(0.125, 0.25,0.5 g/kg) were significantly or partially reduced, the activities of SOD and GSH-Px. were increased, the contents of TNF-α, IL-1β and TGF-β in kidney tissues were significantly reduced(P<0.05 or P<0.01). Pathological examination by HE staining showed that AGTF(0.25,0.5 g/kg) significantly or partially alleviated the thickening of the basement membrane, the local interstitial inflammatory cell infiltration, and the fibrous tissue proliferation in the interstitium of the diseased area.Conclusion: AGTF has a good anti-hyperuricemia and renal function protection, the mechanism may be related to its anti oxidation stress function and inhibition of related inflammatory pathways.