两种不同胰岛素抵抗状态的大鼠高脂联素血症产生的机制研究

A pilot study on mechanisms of hyperadiponectinemia in two rat models with different in vivo insulin sensitivity

目的:初步探讨胰岛素抵抗的Zucker肥胖大鼠(ZF鼠)及嘌呤霉素(PA)诱导的肾病综合征(DN)大鼠高脂联素(ADPN)血症的产生机制。方法:8周龄肥胖Zucker大鼠(ZF大鼠)正常饮食4周,及Wistar大鼠腹腔注射PA后10d留取血、24h尿标本,检测血脂系列、ADPN、白蛋白(ALB)及24h尿白蛋白排泄率(UAER);并行多次取样的静脉糖耐量试验(FSIVGTT),根据Bergman微小模型法计算胰岛素敏感性指数(SI)及葡萄糖效应指数(SG);留取大鼠附睾白色脂肪组织称重。分析ADPN与各指标的相关性。结果:ZF大鼠及PA注射大鼠ADPN水平均显著高于对照组[(7.44±1.23)mg/Lvs(2.44±0.33)mg/L及(8.64±0.88)mg/Lvs(2.95±0.46)mg/L,P<0.0)]。ZF大鼠SI、SG显著降低且与ADPN负相关;DN大鼠SI、SG与对照鼠比较无明显变化,且与ADPN无相关性。两种大鼠模型均有明显高脂血症并与ADPN正相关。ZF鼠及DN鼠尿白蛋白排泄显著增多[(64.8±14.2)mg/24hvs(14.9±14.6)mg/24h及(275.1±64.5)mg/24hvs(15.4±4.5)mg/24h,P<0.01]且与ADPN显著正相关。ZF大鼠白色脂肪比例高于对照鼠,但与ADPN升高水平不成比例,DN大鼠白色脂肪组织无增多。两种大鼠肌酐清除率与对照组比较均无显著差别。结论:ZF大鼠及PA注射鼠呈高ADPN血症,胰岛素敏感性与ADPN无关;两种大鼠UAER明显升高可能是高ADPN血症发生的主要机制。

AIM ： To explore the possible mechanisms of hyperadiponectinemia in the insulin - resistant Zucker fatty rats （ZF） and insulin - sensitive nephrotic syndrome rats induced by puromycin aminonucleoside （PA）. METHODS ： 8 - week old Zucker rats were fed with standard rat chow for 4 weeks and Wistar rats were intraperitoneally injected single dose of PA 10 d before experiments. Blood samples and 24 h urines were collected for detecting the lipid profiles, adiponectin （ADPN）, albumin and urine albumin excretion rate （UAER）. A frequently sample intravenous glucose tolerance test （FSIVGTF） was conducted. The insulin sensitivity index （SI） and glucose effectiveness index （SG） were calculated according to Bergman＇s minimal model. Epididymal white adipose tissues were then extracted for weighting. Correlations between ADPN and other parameters were analyzed by Pearson＇s correlation. RESULTS： Both ZF rats and PA - injected rats showed significantly higher plasma ADPN levels compared with their own controls [ （7.44 ±1.23 ） mg/L vs （2. 44 ±0. 33） mg/L and （8. 64±0. 88）mg/L vs （2. 95 ±0. 46）mg/L, respectively, P 〈0. 01 ]. SI and SG were markedly decreased and negatively correlated to ADPN in Zucker rats, but not changed and correlated to ADPN in Wistar rats. Hyperlipidemia was observed in either ZF rats or PA - injected rats and was positively correlated to ADPN levels. Two hyperadiponeetinemic rats showed markedly higher UAER [ （64. 8 ± 14. 2） mg/24 h vs （ 14. 9 ± 14. 6） mg/24 h and （275. 1 ±64. 5 ） Ing/24 h vs （ 15.4 ± 4. 5 ） rag/24 h, respectively, P 〈 0. 01） and positively correlated with ADPN. The ratio of white adipose tissue to body weight was higher in ZF rats than that in their control rats despite its disproportion with ADPN, while it was comparable between PA - injected and normal rats. The renal creatinine clearance rate was not altered in both strains of rats. CONCLUSION： Hyperadiponectinemia is a common property in ZF rats and PA - induced nephrotic syndrome rats, and it can＇t be interpreted by changes of in vivo insulin sensitivity. Markedly increased UAER in both rats is the key mechanism of hyperadiponectinemia.