·糖尿病基础研究·

　　周晓琳 王兆红 王宇辉 沈蔷 张玲 管又飞 刘国庆 黄薇

　　基金项目：国家自然科学基金面上项目(30870992)

　　作者单位：100083北京大学医学部心血管研究所(周晓琳、王兆红、王宇辉、沈蔷、张玲、刘国庆、黄薇)，北京大学医学部生理学系(管又飞)

　　通讯作者：黄薇，E-mail:huangwei@bjmu.edu.cn

　　【摘要】目的探讨脂蛋白脂酶(LPL)基因缺陷对小鼠1型糖尿病(T1DM)肾病早期病变的影响。 方法雄性LPL基因缺陷杂合子(LK)和野生型(WT)小鼠腹腔注射链脲佐菌素(STZ)，造成T1DM模型后4个月检测相应指标的改变。 结果糖尿病组血糖、血浆TG及TC、肾重/体重比、肌酐清除率(Ccr)、24 h尿白蛋白(UAlb)含量、肾小球表面积均高于非糖尿病组。糖尿病LK组(DLK)与糖尿病WT组(DWT)相比，血浆TG水平、UAlb及血压均增高(P<0.05)。与TG合成相关的核转录因子固醇调节元件结合蛋白-1c(SREBP-1c)基因在DLK组比DWT组表达明显增加(P<0.05)，但肾TG含量无改变。 结论LPL基因缺陷促进T1DM小鼠UAlb含量及血压升高，加重T1DM早期的进展。

　　【关键词】脂蛋白脂酶;基因缺陷;糖尿病，1型;糖尿病肾病;尿白蛋白;脂质代谢

　　doi:10.3969/j.issn.1006-6187.2012.01.020

　　Lipoprotein lipase gene deficiency accelerates early renal dysfunctions in type 1 diabetic miceZHOU Xiao-lin, WANG Zhao-hong, WANG Yu-hui，et al.Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing 100083, China

　　Corresponding author: HUANG wei, E-mail: huangwei@bjmu.edu.cn

　　【Abstract】ObjectiveTo investigate the effect of lipoprotein lipase (LPL) gene deficiency on early stage of type 1 diabetic nephropathy (DN) in mice. MethodsAt 4 months after induction of diabetes by STZ, plasma and renal parameters were examined in heterozygous LPL knock out (LKO) and wide-type (WT) mice. Results(1)Compared with control groups, diabetic groups showed the increased levels of creatinine clearance rate, 24-hour urinary albumin excretion (UAE) and glomerular surface area，which suggested it was at the incipient stage of DN. (2)Plasma triglyceride(P<0.05), UAE(P<0.01)and blood pressure (P<0.05)increased in diabetic LKO (DLKO) mice than in diabetic WT (DWT) mice. (3)Real time PCR analysis showed that renal LPL mRNA expression was decreased in LPL deficiency group and diabetes group. Expression of sterol regulatory element binding protein-1c was up-regulated in DLKO mice compared with DWT mice (P<0.05), but renal lipid deposition didn’t differ between 2 groups. ConclusionsLPL gene deficiency increases albuminuria and blood pressure in type 1 diabetic mice, suggesting LPL gene deficiency may enhance development of early stage of DN in mice.

　　【Key words】Lipoprotein lipase;Gene deficiency; Diabetes mellitus, type 1; Diabetic nephropathy; Albuminuria; Lipid metabolism