IQGAP1在血管紧张素Ⅱ输注大鼠模型肾小球中的表达及意义

目的研究血管紧张素Ⅱ（angiotensin11，AngⅡ）输注及替米沙坦干预对大鼠肾小球IQdomainGTPase—activatingproteinl（IQGAPl）表达的影响，并探讨IQGAPl在AngII诱导肾小球损伤中的作用。方法36只SPF级雄性Wistar大鼠随机分为生理盐水输注组、AngⅡ输注组和替米沙坦干预组，每周末测量大鼠血压及24h尿蛋白量，分别于14、28天处死大鼠取肾，光镜、电镜观察肾组织病理学及超微结构改变；免疫组织化学法、免疫荧光法及免疫印迹法检测IQGAPl在肾小球的表达及分布。结果AngII输注7天时大鼠出现显著的血压升高和尿蛋白量增加，且随输注时间的延长，血压及尿蛋白量进行性增高。替米沙坦干预可显著降低血压，并减少尿蛋白量。肾组织病理学显示AngII输注组出现轻度系膜细胞增殖和系膜基质增加，且超微结构显示足细胞裂隙膜变窄，足突融合，替米沙坦干预可显著减轻上述病理改变。生理盐水输注组IQGAPl低水平表达并沿毛细血管袢呈线性分布，AngII输注后IQGAPl表达量显著增加（P〈0．05），而替米沙坦干预可显著抑制IQGAPl的表达上调（P〈0．05）；相关分析显示IQGAPl表达量与尿白蛋白量呈正相关（r=0．645，P〈0．05）。结论IQGAPl表达上调可能在AngⅡ诱导肾小球损伤中发挥重要作用。

The Significance of Elevated Giomerular IQGAP1 Expression in Model of Angiotensin II Infusion.

Objective To evaluate the effect of AngII on glomerular expression of IQ domain GTPase - activating proteinl （ IQGAP1 ） and investigate the possible effects of IQGAP1 on AugII - induced glomerular damage. Methods Thirty - six male Wistar rats were randomly divided into 3 groups：nomal saline infusion group, AngII infusion group and Telmisartan intervention group. The systolic blood pressure and 24 hour urinary protein were measured every week. Kidneys were collected when the animals were sacrificed at day 14, 28 respectively. Renal pathological changes were observed under light microscope and electron microscope. The glomerular expression of IQGAP1 was evaluated by Immunohistochemistry, immunofluorescence and western blotting. Results AnglI -infused rats developed sig- nificant hypertension as well as proteinuria, and podocyte abnormality and mesangical proliferation were presented,which were alleviated with telmisartan intervention. Distribution of IQGAP1 was linear along the capillary loop, which had no noticeable difference among the three groups. The expression of glomerular IQGAPI significantly increased in AngtI - infused rats as compared with that in nomal saline - infused rats, and Telmisartan administration preventd the tendency effectively （P 〈 0.05）. Moreover, significantly positive correlation was found between the expressin of IQGAP1 and the amount of 24h urinary protein （ r = 0. 645, P 〈 0.05 ）. Conclusion The enhanced expres- sion of IQGAP1 may play an important role in AnglI - induced glomerular damage.