Bidani A K, Griffin K A, Plott W, Schwartz M M
Loyola University Medical Center, Maywood, IL 60153.
J Lab Clin Med. 1993 Sep;122(3):284-91.
Genetic factors have been implicated in the development and progression of glomerulosclerosis and nephron loss in both experimental animals and in humans. The influence of a differing genetic predisposition to hypertension was examined in the remnant kidney (RK) model of progressive glomerulosclerosis. Dahl salt-sensitive (S) and salt-resistant (R) rats fed a normal salt diet underwent either sham surgery or approximately 5/6 renal ablation and were studied 2 to 3 weeks later. Renal ablation resulted in significantly more severe hypertension in RK-S rats (205 +/- 6.3 mm Hg, mean +/- SEM) compared with RK-R rats (153 +/- 3.5 mm Hg; p < 0.01). Renal autoregulatory ability, a protective mechanism against renal transmission of systemic hypertension, was normal in both S and R rats with intact renal mass. Renal ablation resulted in similar impairments of renal autoregulatory ability in both strains. However, striking differences in the severity of renal microvascular and glomerular injury were observed between the remnant kidneys of S and R rats, paralleling the differences in the severity of hypertension. The RK-S rats exhibited acute fibrinoid necrosis and thrombosis of glomerular capillaries, arterioles, and small arteries, whereas only mild segmental glomerulosclerosis lesions were observed in a small percentage of glomeruli in the RK-R rats. The intact kidneys of both strains were essentially free of glomerular or vascular lesions. These data suggest that a genetic predisposition to hypertension is a major determinant of the severity of hypertension that follows severe reduction of renal mass and the severity of the resulting hypertension, in turn, critically influences the severity of glomerular injury in the RK model.
遗传因素在实验动物和人类的肾小球硬化及肾单位丢失的发生和发展过程中均有涉及。在进行性肾小球硬化的残余肾（RK）模型中，研究了不同的高血压遗传易感性的影响。给正常盐饮食的 Dahl 盐敏感（S）大鼠和盐抵抗（R）大鼠进行假手术或约 5/6 肾切除，2 至 3 周后进行研究。与 RK-R 大鼠（153±3.5 mmHg；p<0.01）相比，肾切除导致 RK-S 大鼠的高血压明显更严重（205±6.3 mmHg，平均值±标准误）。肾自身调节能力是一种防止全身性高血压向肾脏传导的保护机制，在肾质量完整的 S 大鼠和 R 大鼠中均正常。肾切除在两种品系中导致类似的肾自身调节能力损害。然而，在 S 大鼠和 R 大鼠的残余肾之间观察到肾微血管和肾小球损伤严重程度的显著差异，这与高血压严重程度的差异平行。RK-S 大鼠表现出肾小球毛细血管、小动脉和小动脉的急性纤维蛋白样坏死和血栓形成，而在 RK-R 大鼠中仅在一小部分肾小球中观察到轻度节段性肾小球硬化病变。两种品系的完整肾脏基本没有肾小球或血管病变。这些数据表明，高血压的遗传易感性是肾质量严重减少后高血压严重程度的主要决定因素，而由此产生的高血压严重程度反过来又严重影响 RK 模型中肾小球损伤的严重程度。
