免疫抑制剂 FK506所致血糖升高副作用的机制研究

摘要

目的：探讨FK506对血糖调节的副作用，并研究其机制。方法：健康SD大鼠12只，随机分为2组：对照组（生理盐水，1 mL· kg -1· d-1）、给药组（FK506，1 mg· kg-1· d-1）。每天监测体重，每2 d测空腹血糖。在第15天取脂肪组织，实时荧光定量PCR检测脂联素（adiponectin）、瘦素（leptin）、内酯素（visfatin）、抵抗素（resistin）、视黄醇结合蛋白4（RBP4）及氧化物酶体增殖物激活受体γ（PPAR-γ）mRNA的表达；Western blotting 检测PPAR-γ及脂联素蛋白的表达。结果：第10天开始，给药组大鼠空腹血糖逐渐升高，显著高于对照组（ P＜0.05）；第14天，给药组空腹血糖由（5.10±0.62） mmol/L升到（7.73±0.73） mmol/L，对照组空腹血糖无明显变化；与对照组相比，给药组大鼠脂肪组织adiponectin和leptin mRNA的表达量显著降低（P＜0.01），而visfatin、resis-tin和RBP4 mRNA表达明显升高（P＜0．05）；与对照组相比，给药组脂肪组织PPAR-γmRNA表达量降低（P＜0.01）；与对照组相比，给药组脂肪组织PPAR-γ及脂联素蛋白表达量明显降低（P＜0．01）。结论：FK506可能通过抑制PPAR-γ的表达，影响脂肪因子的表达，影响血糖。%[ABSTRACT]AIM:ToinvestigatetheeffectofimmunosuppressantFK506onserumglucoseinratsandtoex-plore its mechanism .METHODS: Sprague-Dawley rats ( n =12 ) were randomly divided into drug group and normal group.The rats in drug group were intraperitoneally injected with FK 506 at dose of 1 mg· kg-1 · d-1 and the rats in nor-mal group received saline (1 mL· kg-1 · d-1 , ip) for 14 d.The fasting weight and fasting glucose were regularly meas-ured every 2 d.Visceral fat was isolated from the rats at the end of experiment .The mRNA expression of adiponectin , lep-tin, visfatin, resistin, retinol-binding protein 4 ( RBP4) and peroxisome proliferator-activated receptors γ( PPAR-γ) was determined by real-time fluorescence quantitative PCR .The protein expression of PPAR-γand adiponectin was measured by Western blotting .RESULTS:Compared with normal group , the concentration of fasting blood glucose in model group was significantly increased from the 10th day (P<0.05).At day 14, the fasting blood glucose of the model group increased from (5.10 ±0.62) mmol/L to (7.73 ±0.73) mmol/L.No significant change of blood glucose in normal group between the 10th day and the 14th day [from (4.66 ±0.32) mmol/L to (5.80 ±0.10) mmol/L] was observed.Compared with normal group , the mRNA expression of PPAR-γ, adiponectin and leptin in the adipose tissue of model group was signifi-cantly decreased ( P <0.01 ) , whereas the expression of visfatin , resistin and RBP4 was significantly increased ( P <0.05).Compared with normal group, the expression of PPAR-γand adiponectin in model group was decreased (P <0.01).CONCLUSION:FK506 may decrease the expression of PPAR-γto change the expression of adipocytokines and induce hyperglycemia in rats .