高血压微量蛋白尿形成与血管及肾小球损害的关系

Relationship of hypertensive microalbuminuria and endothelial and glomerular impairment

目的 :探讨高血压病微量蛋白尿的形成机制及其与血管内皮、肾小球损害的联系。方法 :以高血压鼠(SHR)和正常血压鼠 (WKY)为对象 ,测量不同龄 (三月和八月 )鼠尾动脉压、尿蛋白和肾功能以及在电子显微镜下血管内皮和肾小球超微结构的不同表现 ,并用卢沙坦 (Losartan)治疗 5月后观察其改变。结果 :与同龄WKY比较 ,三月龄SHR电镜下已有血管内皮损伤及内皮增生肥大 ,肾小球基底膜亦见轻度增厚 ,但血肌酐未升高 ,仅有尿蛋白增高 ,与血压及血管内皮病变呈正相关 ;八月龄SHR无论血管内皮和肾小球均损害严重除基底膜增厚外还有系膜细胞增生肥大 ,血肌酐仍无变化 ,尿蛋白增高与血管内皮和肾小球病变密切相关 ,与血压无显著相关。经Losartan治疗后尿蛋白明显减少 ,血管内皮、系膜细胞的过度肥大被有效地抑制。结论 :高血压蛋白尿的出现与靶器官损害密切相关 ,早期可能是血流动力学负荷增加或 /和全身内皮功能障碍的一个局部表现 ,后期则主要与肾小球硬化及血管重塑有关 ,Losartan在降压的同时还能保护血管、肾脏 。

Objective To investigate the relationship between hypertensive microalbuminuria and vascular endothelial and glomerular impairment. Methods The animals were divided into the normotensive group (WKY Rat), hypertensive treated group (SHR with losartan) and untreated group(SHR). The blood pressure, level of microalbuminuria, and renal function were measured. In addition, endothelium of the mesenteric artery and glomerular mesangial cells were observed with the transmission electronic microscope in three and eight month old rats respectively. Results Significantly increased microalbuminuria was shown in SHR, which was correlated with the blood pressure and vascular endothelial volume density. Early impairment of vascular endothelium and the glomerular basement membrane was demonstrated in three month old SHR. However, there was no significant difference in glomerular mesangial cells and renal function between SHR and WKY rats. In the eight month old untreated group, the volume density of glomerular mesangial cells increased significantly, which indicated a further impairment of hypertension. The level of microalbuminuria was not correlated with the blood pressure. Compared with the untreated group, the hypertensive treated group showed a decreased volume density of vascular endothelium and glomerular mesangial cells, which was accompanied with a reduction of microalbuminuria. Conclusion The mechanism which causes microalbuminuria in hypertension may vary with the severity of the hypertensive condition. At the early stage, the haemodynamics mechanism seems to be the most plausible cause of microalbuminuria, whereas at the severe stage, glomerular damage and vascular remodeling are likely to play the key role. Losartan can inhibit those deteriorations besides blood pressure lowering.