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机构地区:[1]天津医科大学代谢病医院糖尿病肾病血液透析科卫生部激素与发育重点实验室,300070
出 处:《中华糖尿病杂志》2015年第2期115-119,共5页CHINESE JOURNAL OF DIABETES MELLITUS
基 金:国家自然科学基金(30971393,81070645);天津市科技支撑重点项目(13ZCZDSY01300);天津市自然科学基金项目(10JCYBJC12000);天津市卫生局科技基金重点项目及一般项目(09KZ01,09Kz89)
摘 要:目的观察不同时长B2糖蛋白1(β2-GP1)对链脲佐菌素(STZ)诱导的糖尿病鼠肾组织病理学改变及转化生长因子β1(TGF-β1)表达水平的影响。方法以48只雌性BALB/c小鼠为对象,持续喂养8周高糖高脂饮食,后腹腔注射STZ(80mg/kg),1周后以随机血糖≥16.7mmol/L视为成功建立糖尿病小鼠模型。采用随机数字表法将成模糖尿病小鼠分为模型组(12只)和β2-GP1干预组(20μg β2-GP1干预3周及6周组,各12只),并设正常对照组(12只),干预3周及6周后检测肾组织TGF-β1分布及。肾皮质TGF—β1mRNA及蛋白表达水平。组间比较采用单因素方差分析,进行方差齐性检验,组间两两比较采用SNK.g检验。结果B2.GPI干预组能够明显减低肾皮质TGF-β1mRNA表达水平(3.14±0.14、1.98±0.11比6.07±0.22,q=18.037、28.454,均P〈0.05)及蛋白表达水平(0.66±0.07、0.40±0.05比1.44±0.08,q=12.757、16.454,均P〈0.05)。结论β2-GP1可抑制STZ诱导的糖尿病小鼠肾脏TGF-β1的表达,并具有一定的时间依赖性,该作用可能与其肾脏保护作用有关。Objective To explore the effects of β2-glycoprotein I (β2-GP1)on renal tissue pathologic change and transforming growth factor β1 (TGF-β1 )expression in streptozotocin (STZ)induced diabetic mice. Methods Forty-eight female BALB/e mice were fed with high fat chow diet for 8 weeks. Then the mice were injected intraperitoneally with STZ (80 mg/kg). Diabetic mice were confirmed by the criterion that plasma glucose concentration was higher than 16.7 mmol/L after 1 week from injection date. The mice were randomly divided into a diabetes mellitus (DM)group(n=12), treatment with β2-GP1 (20 μg) groups (treated for 3 weeks or 6 weeks, each n=12) and a normal control group (n=12). The changes of glomerular structure and expression of TGF-β1 in renal cortical were detected by immunohistochemical techniques, quantitative real-time PCR and Western blotting. Single factor analysis of variance (ANOVA) was applied to perform the homogeneity of variance test among the groups, and SNK-q test were used to analyze the difference between two groups. Results β2-GP1 improved renal dysfunction and kidney structure damage, and decreased TGF-β1 mRNA expression (3.14±0.14,1.98±0.11 vs 6.07±0.22, q= 18.037, 28.454, respectively, all P〈0.05) and protein expression (0.66±0.07,0.40±0.05 vs 1.44±0.08, q=12.757, 16.454, respectively, all P〈0.05) in STZ-induced diabetic. Conclusion β2-GP1 plays a role of renal protecting by inhibiting the expression of TGF-β1 in renal tissues of the STZ-diabetic mice, may in time- dependent way.
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