单侧肾切除及微渗透泵灌注血管紧张素Ⅱ诱导小鼠肾纤维化与高血压模型的建立

研究报告

单侧肾切除及微渗透泵灌注血管紧张素II诱导小鼠肾纤维化与高血压模型的建立

陈建，曾莉， 陈刚，何立群

(上海中医药大学附属曙光医院，上海200021)

【摘要】目的建立单侧肾切除及微渗透泵灌注血管紧张素II诱导小鼠肾纤维化模型。方法将36只雄性野生型 c57BL/6小鼠随机分为3组正常组、模型组、生理盐水对照组，每组12只。正常组不做处理，模型组行单侧肾切除及微渗透泵灌注血管紧张素II，生理盐水对照组行单侧肾切除及微渗泵灌注生理盐水。观察造模前及造模后第2周、第4周小鼠血压，及造模4周后的24 h尿蛋白定量、血肌酐、尿素氮、肾脏病理。结果实验第二周时，生理盐水对照组(P<0.05)及模型组(P<0.01)的血压较正常组升高，模型组较生理盐水对照组也升高(P<0.05)；实验第四周时，模型组血压较正常组(P<0.01)及生理盐水对照组(P<0.05)均升高。模型组的血肌酐、血尿素氮数值较正常组均上升(P<0.05)；模型组24 h尿蛋白定量数值较正常组与生理盐水对照组的升高(P<0.01)，模型组HE染色结果近曲小管上皮细胞浑浊肿胀；模型组Masson染色结果胶原纤维阳性率显著高于正常组和生理盐水对照组(P<0.05)。结论 单侧肾切除+微渗透泵灌注血管紧张素II可以成功建立小鼠肾纤维化模型及高血压模型。

【关键词】血管紧张素II；高血压；肾纤维化；高血压肾损害；

[基金项目]国家自然科学基金(81173219)；上海市科学技术委员会科研计划项目(编号:11ZR1437700)；国家临床重点专科，国家中医药管理局重点学科；上海市中医药事业发展三年行动计划项目(ZYSNXD-CC-YJXYY)。

[作者简介]陈建(1987-)，男，研究方向：中西医结合治疗慢性肾脏病的临床与基础研究。E-mail: 13120557664@163.com。

[通讯作者]陈刚(1973-)，男，研究方向：中西医结合诊治肾病的临床和实验研究。Email: 53821650@163.com。

【中图分类号】R33【文献标识码】 A

doi:10.3969.j.issn.1671.7856. 2015.002.007

Establishment of a mouse model of renal fibrosis and

hypertension induced by unilateral nephrectomy and

infusion of angiotensin II using a micro-osmotic pump

CHEN Jian, ZENG Li, CHEN Gang, HE Li-qun

( Shuguang Hospital，Shanghai University of TCM，Shanghai 200021, China)

Abstract【】ObjectiveTo establish a mouse model of renal fibrosis and hypertension induced by unilateral nephrectomy and infusion of angiotensin II using a micro-osmotic pump. Methods Thirty-six 8-week old wild type male c57BL/6 mice were randomly divided equally into three groups. The normal group was not treated, model group underwent unilateral nephrectomy and infusion of angiotensin II using a micro-osmotic pump, and the saline control group underwent unilateral nephrectomy and infusion of physiological saline using a micro-osmotic pump. Blood pressure was measured before and two and four weeks after modeling. The 24 h urine protein quantity, serum creatinine (Scr), and blood urea nitrogen (BUN) were measured, and renal pathology was examined at 4 weeks after modeling. ResultsAt 2 weeks of the experiment, the blood pressure in the saline control group and model group was significantly higher compared with that of the normal group (P<0.05, P<0.01), and the blood pressure of the model group was significantly higher than that of the saline control group (P<0.05). Four weeks after operation, the blood pressure in the model group was still higher than that of the normal group (P<0.01) and the saline control group (P<0.05). Both the levels of Scr and BUN in the saline control group and model group were significantly higher than those of the control group (P<0.05, P<0.05). The 24 h urine protein quantity in the model group was markedly higher compared with that of the saline control group and normal group (P<0.01). The pathological examination showed that proximal tubular epithelial cells were swollen in the model group. Histology using Masson staining showed that the positive rate of collagen fibers in the model group was significantly higher than that of the normal group and saline control group (P<0.05).ConclusionsOur results demonstrate that a mouse model of renal fibrosis and hypertension can be successfully established by unilateral nephrectomy and infusion of angiotensin II using a micro-osmotic pump.

【Key words】Angiotensin II; Hypertension; Renal fibrosis; Hypertension; Renal damage; Mouse

肾脏是高血压病最重要、最常见的靶器官之一。长期的高血压可导致高血压性肾损害，特别是恶性高血压，如不干预最终将发展至肾功能衰竭。据文献报道，国内外由高血压造成的肾脏损害进入慢性肾功能不全的患者人数，呈逐年上升趋势[1，2]。肾纤维化是高血压产生肾脏损害的表现形式，也是慢性肾脏病发展为终末期肾衰竭的共同通路。……