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目的酵母联合高果糖饮食对大鼠嘌呤代谢影响及作用机制研究。方法选用雄性Wistar大鼠40只,随机分为四组,每组10只,分别为空白对照组、酵母对照组、酵母氧嗪酸钾组(高尿酸血症传统模型组)、酵母果糖组。分别在第2、4、6、8 w末剪尾取血,测定各组的血清尿酸(SUA)、血清尿素氮(BUN)、血清肌酐(SCr)水平。在第8w周末时,收集24h尿液,测定尿中尿酸(UUA)、肌酐(UCr),计算尿酸清除率(CUA)和肌酐清除率(CCR),测定血清腺苷脱氨酶(ADA)和黄嘌呤氧化酶(XOD)活性,并进行肾脏组织学病理切片观察。采用Western blotting检测大鼠肾脏有机阴离子转运子1(OAT1)、肾脏尿酸盐转运体(RST)、葡萄糖转运蛋白9(GLUT9)的蛋白表达水平。结果实验第2、4、6、8 w末,酵母果糖组大鼠血清SUA水平分别达到345.9、403.7,447.2和451.4μmol/L。与空白对照组相比,酵母果糖组SUA水平分别升高了66.5%、33.8%、37.5%和69.8%;而酵母氧嗪酸钾组(传统模型组)大鼠SUA水平也显著升高,显示造模成功。在第8 w,酵母果糖组与酵母氧嗪酸钾组大鼠SUA水平分别是空白对照组2.24倍和2.17倍,显示果糖具有氧嗪酸钾类似的促进尿酸生成作用。与嘌呤代谢相关的XOD和ADA活性分析显示,酵母果糖组大鼠血清和肝匀浆中XOD活性明显高于空白对照组(均P<0.05);而ADA活力也显著高于空白对照组(均P<0.05)。与空白对照组相比,酵母果糖组大鼠24h尿量明显增加,CUA明显降低(均P<0.05)。组织学分析显示,在实验第8 w,酵母果糖组大鼠肾小管管腔间质偶见结晶物沉积,无明显纤维化,肾小管、肾小球组织结构无明显异常。Western blotting结果显示,与空白对照组相比,酵母果糖组大鼠肾脏OAT1水平明显下降,RST水平明显升高(均P<0.05)。结论果糖可增强酵母诱发高尿酸血症的作用,对肾的副作用较小,可作为开展嘌呤代谢研究的良好模型;但摄入高嘌呤食物时应避免果糖过量摄入。
Effects of Yeast Plus High Fructose Diet on Purine Metabolism in Rats and Its Mechanism. Methods Forty male Wistar rats were randomly divided into four groups with 10 rats in each group. They were blank control group, yeast control group, yeast potassium ox oxazine group (traditional model group with hyperuricemia) and yeast fructose group. At the end of the 2nd, 4th, 6th and 8th week, blood was collected from the tail to determine the levels of serum uric acid (SUA), serum urea nitrogen (BUN) and serum creatinine (SCr). At the end of the 8th week, 24-hour urinalysis was collected and the uric acid (UUA) and creatinine (UCr) were measured to calculate the uric acid clearance (CUA) and creatinine clearance rate (CCR) Xanthine oxidase (XOD) activity, and histological examination of renal histology. Western blotting was used to detect the protein expression of OAT1, RST and GLUT9 in rat kidneys. Results At the end of the 2nd, 4th, 6th and 8th week, the serum SUA levels in the yeast fructose group were 345.9, 403.7, 447.2 and 451.4μmol / L, respectively. The levels of SUA in yeast fructose group increased by 66.5%, 33.8%, 37.5% and 69.8%, respectively, compared with those in the blank control group. The levels of SUA in the yeast oxonic acid potassium group (traditional model group) Modeling success. At the 8th week, SUA levels in yeast fructose group and yeast oteracil potassium group were 2.24 and 2.17 times higher than those in blank control group, respectively. Fructose had the similar effect of oxonic acid potassium on uric acid production. Analysis of XOD and ADA activity related to purine metabolism showed that XOD activity in serum and liver homogenate of yeast fructose group was significantly higher than that of blank control group (all P <0.05), while ADA activity was also significantly higher than that of blank control group P <0.05). Compared with the blank control group, the urinary excretion of 24h in the yeast fructose group increased significantly and the CUA decreased significantly (all P <0.05). Histological analysis showed that in the 8th week of experiment, the renal tubular interstitium of yeast fructose group was deposited with no obvious fibrosis, and the structure of renal tubules and glomerulus was not abnormal. Western blotting results showed that compared with the blank control group, the level of OAT1 in the kidney of the yeast fructose group was significantly decreased and the RST level was significantly increased (all P <0.05). Conclusion Fructose can enhance the role of yeast in inducing hyperuricemia, with less side effects on the kidney. It can be used as a good model for the study of purine metabolism. However, excessive intake of fructose should be avoided when consuming high-purine foods.