痛风的诊治进展-学习班.ppt

痛风的流行病学 高尿酸血症 痛风 西方国家 5%—20% 0.5--1% 中 国 10.1% 0.34% 近年来患病率呈上升趋势！ 痛风是高等动物特有的疾病 Why our body produce urate? Why nonprimates and most mammals with much lower serum urate（10 times lower）? How does hyperuricemia lead to an inflammatory response to urate crystals? 尿酸的生理功能 Urate may serve as primary antioxidant in human blood, remove singlet oxygen and radicals as effectively as vitamin C. Level of plasma uric acid (300 mM) are approximately 6 times those of vitamin C in humans May play a role in immunity as an adjuvant. Only crystalline uric acid can serve as an adjuvant (shi et al. 2003) Low levels of uric acid led to delayed tumor rejection and treating the tumor mice with uric acid enhanced the rate rejection Absence of Uricase in humans Humans –the only mammals gout develop spontaneously In most fish, amphibians and nonprimate mammals, UA generated from purine metabolism undergoes oxidative degradation through uricase enzyme, producing more soluble compound allantoin. In humans, uricase gene is crippled by 2 mutations that introduce premature stop codons Absence of uricase, combined extensive reabsorption of filtered urate, resulting urate levels in human plasma approximately 10 times than other mammals (30-59 mmol/L) Hyperuricemia has detrimental in humans-pathogenetic roles in gout and nephrolithiasis and putative roles in hypertension and other CV disorders. - the fact that loss of uricase occurred in the same era suggests that it may have conferred a survival advantage during that period - our ancestors in the Miocene era were mainly limited to a diet of fruits and grasses (low in sodium); this low sodium diet may have led to a hypotensive “crisis” - loss of uricase and accumulation of uric acid might have compensated for Hypotension - biped more dependent on blood pressure to maintain cerebral perfusion the experiment… - rats fed a low-sodium diet then treated with oxonic acid, a uricase