鹅去氧胆酸对高果糖喂养大鼠肾组织中法尼醇X受体和小异源二聚体伴侣的影响

The effects of chenodeoxycholic acid on the expression of farnisoid X receptor and small heterodimer partner in the kidney of high-fructose-fed rats.

目的通过观察高果糖喂养大鼠肾组织中法尼醇X受体(FXR)及小异源二聚体伴侣(SHP)的表达,探讨高果糖致肾损伤的机制。通过鹅去氧胆酸的干预,初步探讨其保护作用机制。方法将48只大鼠分为正常对照组(对照组,n=16),高果糖组(n=16)及鹅去氧胆酸组(n=16),8周及16周时分批处死,检测各组大鼠的肾功能、空腹血糖、血脂及24 h尿微量白蛋白;检测大鼠肾皮质三酰甘油含量;免疫组织化学染色检测FXR的表达和定位;FXR及SHP的表达采用实时荧光定量PCR分析技术,并应用Western-blot法分析FXR及SHP的蛋白表达。结果与对照组比较,高果糖组大鼠左肾重/体重,血中三酰甘油和极低密度脂蛋白水平明显升高,24 h尿白蛋白增加,肾组织中三酰甘油水平明显增高,且随时间延长而加重(P<0.05);高果糖组大鼠肾组织FXR表达明显下调,FXR及SHP的基因及蛋白表达明显减少,且随时间延长其表达减弱(P<0.01)。鹅去氧胆酸组上述指标明显改善(P<0.05)。结论高果糖饮食喂养可导致大鼠高三酰甘油血症、高极低密度脂蛋白血症、高尿酸血症和尿微量白蛋白水平增加,可引起大鼠肾皮质三酰甘油蓄积,使大鼠肾组织FXR及SHP的基因及蛋白表达明显减少,从而使肾脏脂质合成增加,进而导致肾脏损伤。鹅去氧胆酸可上调高果糖喂养大鼠肾组织FXR及SHP的基因及蛋白表达,减轻肾损伤。

Objective To observe the effects of high -fructose -feeding on farnisoid X receptor （FXR） and small heterodimer partner （SHP） in rat kidney so as to explore the mechanism of renal injury and to investigate the protective effect of chenodexoycholic acid （CDCA） intervention. Methods Forty - eight healthy male Wistar rats were randomly divided into three groups （n = 16） ： normal control group, high fructose group and CDCA group. The rats were sacrificed at the end of 8 and 16 weeks. The BUN, Scr, UA, fast glucose, lipid concentration, and urinary microalbumin were assessed. Triglyceride in renal cortices was also measured. The expression and localization of FXR was assessed by immunohistochemistry, while the mRNA and protein expression of both FXR and SHP was measured by real time PCR and western - blot, respectively. Results The left kidney weight/body weight, plasma triglyceride （ TC）, very - low - density - lipoprotein （VLDL） and UA, urinary microalbumin, and renal cortex triglycerides were significantly increased in high fructose group （ P 〈 0. 05 ） , with no significant effects on the renal function and fast glucose （ P 〉 0. 05 ）. Furthermore, the renal gene and protein expression of FXR and SHP in high fructose group were significantly down - regulated （P 〈 0. 01 ）. CDCA treatment could significantly reverse these high fructose - induced changes （ P 〈 0. 01 ）. Conclusion High - fructose feeding can lead to hypertriglyceridemia, hyper - very - low - density - lipoproteinemia, hyperuricemia and elevated urinary microprotein in rats ; also the lipid accumulation in rat kidney and down - regulation of renal FXR and SHP. CDCA intervention may reverse these injuries.