免疫抑制剂FK506所致血糖升高副作用的机制研究

 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、resistin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-γ mRNA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。

Mechanisms of hyperglycemia induced by immunosuppressant FK506

AIM：To investigate the effect of immunosuppressant FK506 on serum glucose in rats and to explore 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 FK506 at dose of 1 mg·kg-1·d-1 and the rats in normal group received saline (1 mL·kg-1·d-1, ip) for 14 d. The fasting weight and fasting glucose were regularly measured every 2 d. Visceral fat was isolated from the rats at the end of experiment. The mRNA expression of adiponectin, leptin, 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-γ and 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 significantly 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-γ and adiponectin in model group was decreased (P<001). CONCLUSION：FK506 may decrease the expression of PPAR-γ to change the expression of adipocytokines and induce hyperglycemia in rats.