牛磺酸对高尿酸血症肾病大鼠尿酸生成和排泄的影响及其机制研究

Hyperuricemia caused by metabolic disorder of purine or paraeccrisis of uric acid has become a serious threatening disease to human health and poultry industry. It has been found by our previous research that taurine could significantly lower the levels of blood uric acid, creatinine and urea nitrogen, decrease the deposition of urate in the kidney, indicating that taurine could ameliorate hyperuricemia probably by influencing uricogenesis, uric acid excretion and decreasing the kidney injury, but the mechanisms of which are still unclear. This study aims to discuss the exact effects of taurine on uricogenesis by detecting the enzymes involved in uricogenesis using the method of Elisa and immunohistology. Then effects of taurine on the reabsorption and secretion of uric acid were investigated by detecting the gene and protein expression levels of uric acid transporter in the renal tubular epithelial cells using the method of Real-time PCR and Western-blot. What’s more, the effects of taurine on kidney injury were also approached by detecting the renal functional indexes combined with kidney morphology observation. The exact mechanisms of taurine on regulating uric acid levels were elucidated from the above aspects in order to provide theoretical basis for using taurine in the prevention of human hyperuricemia and the application in the poultry industry.

由于嘌呤代谢紊乱或尿酸排泄障碍导致的高尿酸血症已成为威胁人类健康和禽类生产的重要疾病。课题组前期研究发现，牛磺酸可显著降低高尿酸血症肾病大鼠尿酸，肌酐，尿素氮水平，减少肾组织尿酸盐沉积，提示牛磺酸能改善高尿酸血症，可能是通过影响尿酸的生成和排泄过程、减轻肾损伤来发挥的，但确切作用及机制尚不清楚。本项目拟制备高尿酸血症肾病模型大鼠结合体外细胞培养，通过检测肾功能评价指标结合形态学观察，探讨牛磺酸对高尿酸血症所致肾损伤的作用；应用Elisa、HPLC等方法检测牛磺酸对尿酸生成相关酶和底物的影响，确定牛磺酸调节尿酸生成的关键环节；应用Real-time PCR、Western-blot等方法检测肾小管上皮细胞尿酸转运体的基因、蛋白表达水平，探讨牛磺酸对尿酸重吸收和分泌的影响；最终阐明牛磺酸调节高尿酸血症肾病大鼠尿酸生成和排泄的确切机制，为牛磺酸在防治人类高尿酸血症和养禽业中的应用提供理论依据。

高尿酸血症是由于嘌呤代谢紊乱导致尿酸生成增加或尿酸排泄障碍所引起的疾病，是引发痛风的重要生化基础及最危险因素。随着家禽的集约化饲养，在饲料生产、饲养管理等环节中存在可使血尿酸升高的诸多诱因，导致禽痛风的发病率日益增高，已成为家禽的常见病、多发病之一，严重影响了养殖场的经济效益。同时，伴随人们膳食结构和生活习惯的改变，特别是富含蛋白质和嘌呤的食物摄入增加、过量饮酒，导致高尿酸血症的发病率也日益增加，已成为继糖尿病之后的第二大代谢性疾病。牛磺酸是机体内含硫氨基酸的代谢产物，对机体具有重要的生理、药理和营养功能，是机体内不可缺少的一种生理活性物质。由于牛磺酸对机体无毒副作用，且价格低廉，已作为一种性能优良的食品添加剂，应用于人类生活和畜牧生产中。本项目研究发现，牛磺酸可明显减少高尿酸血症肾病模型大鼠肾脏尿酸盐的沉积，可以通过调节尿酸生成过程中一些酶的活性、排泄过程中尿酸转运体的表达水平而达到降尿酸的作用；同时，在细胞水平上，也证明了牛磺酸可减少尿酸的吸收，且可调节与重吸收相关的转运体基因及蛋白的表达水平，进一步确证了牛磺酸在尿酸排泄过程中的重要作用；此外，牛磺酸的抗氧化、抗炎作用也使其发挥了对肾脏结构及功能的保护作用。本项目研究成果将为牛磺酸在防治人类高尿酸血症及养禽业中的应用提供科学依据，具有十分重要的社会意义和应用前景。