机构地区:[1]天津市人民医院内分泌科,300191 [2]天津医科大学代谢病医院实验室,300070
出 处:《国际内分泌代谢杂志》2012年第4期223-226,230,F0003,共6页International Journal of Endocrinology and Metabolism
基 金:天津市卫生局科技基金资助项目
摘 要:目的探讨脂联素在早期糖尿病肾病中的作用及其可能的作用机制。方法建立链脲佐菌素(STZ)诱导的糖尿病动物模型,随机分为正常对照组(NC组)、糖尿病组(DM组)、吡格列酮治疗组[15mg/(kg·d),PT组]。每周测量体重,每两周测定血糖,于实验第8周末处死大鼠后测定血清脂联素水平、相关生化指标及肾功能指标,同时留取肾皮质液氮冻存与福尔马林固定,应用实时定量逆转录(RT)-PCR方法检测。肾皮质脂联素受体、转化生长因子(TGF)—β1.的mRNA水平,免疫组织化学法测定TGF-β1,蛋白的表达情况。结果与Nc组相比,DM组大鼠血糖、血尿素氮、24h尿量及尿微量白蛋白、肾肥大指数明显升高(P〈0.01),血肌酐含量和血清脂联素水平明显下降(P〈0.01)。与DM组比较,PT组仅在实验前期出现短暂的血糖降低,后期血糖水平差异无统计学意义,但PT组血清脂联素水平升高(P〈0.05),血尿素氮、24h尿量及尿微量白蛋白、肾肥大指数等指标明显下降(P〈0.01)。实时RT—PCR结果显示,与NC组比较,DM组的脂联素mRNA表达量下降,而TGF-β1mRNA表达明显升高;与DM组相比,胛组脂联素mRNA水平升高(P〈0.05),而TGF-β1mRNA表达明显受抑制(P〈0.01)。结论脂联素对糖尿病肾病具有重要作用,吡格列酮可以通过增加脂联素在肾脏的表达来抑制TGF-β1mRNA及蛋白的表达,从而对肾脏发挥独立的保护作用。Objective To investigate the effect of adiponectin on early stage of diabetic nephropathy and the possible mechanism. Methods Murine diabetic models were induced with streptozotocin (STZ). All rats were randomized divided into normal control group( NC group), diabetic group (DM group), and piogli-tazone therapy group( 15 mg · kg^-1 · d^-1 ,PT group). The body weight was measured every week,and blood glucose was determined every two weeks. All rats were killed after 8 weeks, and then serum adiponectin lev-els, related biochemical data and indicators of renal function were measured. At the same time ,the liquid ni- trogen frozen specimens from renal cortex were taken to analyze the level of adiponectin, transforming growth factor(TGF)-β1 mRNA by real time RT-PCR. The expression of TGF-β1 protein was determined by immuno-histochemistry. Results Compared with NC group, the levels of blood glucose, blood urea nitrogen, 24 h urine and urinary mieroalbumin, renal hypertrophy index were significantly higher in DM group ( P 〈 0. O1 ) , whereas the levels of serum ereatinine and adiponectin were significantly lower( P 〈 O. 01 ). Compared with DM group,PT group only had a short-term hypoglycemia during the early stage of experiment. Glucose level in later stage between DM and PT group had no statistical difference. However, in PT group, serum adiponectin level increased (P 〈 0.05 ) while blood urea nitrogen,24 h urine and urinary microalbumin, renal hypertro- phy index decreased significantly (P 〈 0.01 ) compared with DM group. Real-time PCR showed that com- pared with NC group, adiponectin mRNA expression decreased, while TGF-[31 mRNA expression was signifi- cantly enhanced in DM group. Compared with DM group, adiponectin mRNA level in PT group was increased (P〈0.05) ,whereas TGF-β1mRNA expression was significantly inhibited (P 〈0.01). Conclusions Adi-ponectin plays an important role in diabetic nephropathy. Pioglitazone can inhibit the expression of TGF-β1 mRNA
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