中文摘要
高尿酸血症(HUA)发病率高达10%,尚无治疗药,现有治痛风降尿酸药对肝肾有损害。HUA与“肝-肠轴”和“肾-肠轴”的尿酸生成与排泄密切相关。前期研究发现铁皮石斛叶与茎含有类似的黄酮碳苷成分,且能降尿酸、降血压。中医认为“过食肥甘、醇酒厚味、情志失调、起居无常,易运化失司”是HUA的主要病因。模拟人类不良生活方式,采用高脂高糖等饮食制备高尿酸血症伴高血压模型动物。用RT-PCR、Western blot、流式细胞等,从整体、细胞、分子等层面,研究铁皮石斛叶黄酮碳苷对TLR4信号通路多个环节的影响,进一步观察“肝-肠轴”XDH/XOD系统和“肾-肠轴”尿酸转运系统、RAAS的影响,从而减少尿酸生成或促进排泄,并观察其调肠胃和护肝肾功能,系统阐述铁皮石斛叶黄酮碳苷的降尿酸机制及保肝肾等特点,为开发抗高尿酸血症中药新药和铁皮石斛叶充分利用奠定基础;为降尿酸中药的优势与机制研究提供依据。
英文摘要
At present, the incidence of hyperuricemia is increasing year by year(>10%).There is no ideal treatment drugs, which have serious liver and kidney damage. It is believed that liver/kidney-gut axis plays a crucial role in the formation of hyperuricemia. Previous researches show that the stems and leaves of Dendrobium officinaie shared the similar chemical composition(flavone C-glycosides), which could reduce blood pressure and serum uric acid, improve the liver and kidney damage. According to the Dendrobium officinaie is helpful for stomach and can producing fluid, nourishing yin and clearing heat, which can make the source of generation and transformation of the spleen and stomach, and make the congenital foundation sufficient. As the saying goes: improper diet, overeating greasy, excessive drinking, irregular work and rest will lead to dysfunction of the spleen in transport, lost transport department, even to dampness endogenous. So we can infer that leaves of Dendrobium officinaie may reduce the generation of liver and intestinal UA and promote excretion of kidney intestine UA by regulating the intestinal function, protecting the intestinal mucosa barrier, thereby reducing the generation of liver-intestine UA, and promoting excretion of kidney-intestine UA, finally lowering blood pressure and uric acid. In order to get close to a human way of hyperuricemia in animal models, this project selects of three stimulation methods (high sugar, high fat diet, excessive drinking, sleep disorders) to simulate the unhealthy lifestyle’s effects on uric acid and blood pressure. As stated above, methods such as RT-PCR, Western blot and Flow cytometry will be used to make clear the mechanism of flavone C-glycosides from Dendrobium officinaie leaves of prevention and treatment on the hyperuricemia with hypertension caused by unhealthy-life styles and the protectional function of liver and kidney. What’s more, we will illuminate that leaves of flavone C-glycosides from Dendrobium officinaie may reduce the generation of liver and intestinal UA and promote excretion of kidney intestine UA by regulating the intestinal function, protecting the intestinal mucosa barrier, as well as blocking inflammatory cascade reaction mediated by TLR4, thereby reducing the generation of liver-intestine UA, and promoting excretion of kidney-intestine UA, then lowering blood pressure and uric acid. Finally, to lay the foundation for the development of anti hyperuricemia drugs and make full use of Dendrobium officinaie, and provide a new way of thinking for the advantages and mechanism research of lowering uric acid in Chinese traditional medicine.
