缺氧、VEGF及其受体表达在高血压肾损伤中的作用

Hypoxia,VEGF and VEGFR-2 Expression in Hypertensive Kidney Injury

目的:探讨缺氧、VEGF及其受体表达在高血压肾损伤中的作用。方法:将大鼠分为3组:①假手术组;②两肾一夹高血压未治疗组;③两肾一夹高血压降压治疗组。每组8只,观察10周后处死,对未钳夹的右肾进行常规病理、RT—PCR及免疫组化检测。用缺氧探针显示肾组织缺氧情况。结果:高血压组血清肌酐与假手术组比差异无统计意义(P＞0．05),但血压、24h尿蛋白定量、肾小球损伤指数、微动脉壁/腔比均较假手术组有上升(P＜0．01)。假手术组大鼠未钳夹肾髓质有轻度缺氧,但皮质无明显缺氧表现。高血压组髓质和皮质均有明显缺氧(P＜0．01),主要阳性部位在肾小管和病变较严重的肾小球。皮质VEGF、VEGFR-2表达均较假手术组明显升高(P＜0．01),阳性部位与缺氧探针阳性部位分布一致。与未治疗组比较,降压治疗组的血压、24h尿蛋白定量、肾小球损伤指数、肾皮质缺氧状况均有所改善,VEGF、VEGFR-2表达显著下调(P＜0．05)。结论:两肾一夹高血压大鼠模型可作为慢性肾脏缺氧的动物模型。高血压大鼠的肾皮质VEGF及其受体表达上调,并与缺氧部位分布一致,这可能是对组织缺氧的代偿反应,并参与了慢性高血压肾损伤的发生。

Objective：To observed the role of hypoxia, VEGF and VEGFR-2 in hypertensive kidney injury. Methods：Two-kidney-one-clip hypertensive rats were divided randomly into hypertensive group （HT） and antihypertensive group（AH）. Sham rats were as negative controls. Each group had 8 rats. Animals were sacrificed at the 10th week. Results：There was no significant difference of serum creatinine among groups. HT group had higher blood pressure, urine protein excretion rate, glomerular injury score and wall-to-lumen ratio of arteriole than SHAM group（P〈0.01）. HT group also showed anoxic cortex , elevated expression of VEGF and VEGFR-2 compared with SHAM group（P〈0.01）. Hypoxyprobe, VEGF and VEGFR-2 had similar distribution in the cortex of unclipped right kidney, mainly detected in tubules and injured glomeruli. Antihypertensive treatment not only decreased blood pressure, but also improved urine protein excretion, glomerular injury and hypoxia in the cortex（P（0. 05） with downregulating expression of VEGF and VEGFR-2 （P（0. 01 ）. Conclusion： Two-kidney-one-clip hypertensive rat was a feasible model of chronic renal hypoxia. Upregulating expression of VEGF and VEGFR-2 in the cortex of hypertensive rats, consistent to the distribution of hypoxia, may be responses to renal hypoxia and participate in the progression of hypertensive kidney injury.