·糖尿病基础研究·

作者单位：266011青岛市市立医院内分泌科(栾健、张杰涛);青岛大学医学院附属医院肾内科(王艳、马瑞霞)

通讯作者：王艳，E-mail: wangyan@medmail.com.cn

血管内皮生长因子和内抑素在大鼠糖尿病

肾病发病中的作用

栾健王艳张杰涛马瑞霞

【摘要】 目的 研究血管内皮细胞生长因子(VEGF)作为促血管生长因子和内抑素(ENS)作为血管生成抑制因子，在糖尿病肾病(DN)血管生成中的作用。 方法 以正常大鼠为对照，30只雄性Wistar大鼠建成糖尿病模型，分别于糖尿病模型建立2、4、8周观察24小时尿白蛋白排泄率(UAER)，用免疫组织化学染色显示大鼠肾组织VEGF和ENS的表达及半定量分析;用酶联免疫法测定血中VEGF和ENS的浓度，根据DN病理学改变确定DN的血管增生严重性，分析内皮细胞增生、肾小球中弥漫或结节病变及肾小球硬化与VEGF和ENS的关系;采用RT-PCR的 方法 观察大鼠肾脏VEGF和ENS mRNA的表达。 结果 DN大鼠肾组织VEGF和ENS的mRNA和蛋白表达水平明显高于对照组(P<0.05);DN大鼠血清VEGF和ENS水平也明显高于对照组(P<0.05)。DN大鼠UAER与血浆VEGF和ENS相关(r=0.468，P<0.01;r=0.395，P<0.05)，DN大鼠无论在血中还是肾组织免疫组化和RT-PCR都有VEGF和ENS的表达，VEGF的表达与DN血管增生程度密切相关(r=0.404～0.476, P<0.01～0.05)，ENS的表达也与DN严重程度密切相关(r=0.409～0.617, P<0.05～0.01)，血浆VEGF和ENS二者具有正相关性(r=0.484, P<0.01)。 结论 VEGF和ENS与DN血管增生密切相关。

doi:10.3969/j.issn.1006-6187.2011.06.019

The role of vascular endothelial growth factor (VEGF) and endostatin in the pathogenesis of nephropathy in diabetic rats

LUAN Jian, WANG Yan,ZHANG Jie-tao, et al. Department of Endocrinology,Qingdao Municipal Hospital, Qingdao 266011,China

Corresponding author: WANG Yan, E-mail: wangyan@medmail.com.cn

【Abstract】 Objective To investigate the role of VEGF and endostatin in the pathogenesis of nephropathy in diabetic rats. Methods 8 Wistar rats were as a normal control group.30 Wistar rats were studied at 2, 4 and 8 weeks of diabetic state.The urinary albumin excretion rate(UAER) were measured.The expression of VEGF and endostatin in renal tissue were determined by immunohistochemistry. Concentrations of VEGF and endostatin in plasma were measured by enzyme-linked immunosorbent assay. The severity of angiogenesis in diabetic nepnropathy (DN) was quantitated according to the changes of pathology. The correlation of the severity of angiogenesis in DN(the proliferation of endothelium, microaneurysm, K-W nodules and glomerulosclerosis) with VEGF and endostatin was analyzed. The expressions of VEGF and ENS mRNA in renal tissue were detected by RT-PCR at 2, 4 and 8 weeks of diabetic state in both two groups. Results The expressions of mRNA and protein of VEGF and ENS and the serum levels of VEGF and ENS were significantly higher in DN group than in nomal contral group (all P<0.05). The DN rats showed a correlatiom of UAER with plasma VEGF and ENS (r=0.468,P<0.01; r=0.395,P<0.05, respectively), a relationship between angiogenesis and VEGF expression (r=0.404,P<0.05) and a correlation between plasma VEGF and ENS (r=0.484,P<0.01). Conclusion s These Results show that both VEGF and endostatin are correlated with angiogenesis in DN.

【Key words】Vascular endothelial growth factor; Endostatin; Diabetic nephropathy