Saito T, Sato H, Obara K, Yamakage K, Abe K, Furuyama T, Yoshinaga K
Second Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
J Lab Clin Med. 1990 Feb;115(2):165-73.
To study the influence of hypertension on the progression of focal glomerulosclerosis (FGS), we produced an experimental model of FGS in spontaneously hypertensive rats (SHRs) by the combined administration of puromycinaminonucleoside (AMNS) and protamine sulfate (PS). SHRs and normotensive Wistar Kyoto rats as a control strain were given daily injections of subcutaneous AMNS (1 mg/100 gm body weight) and intravenous PS (two separated doses of 2.5 mg/100 mg body weight) for 4 days; they were killed on day 80 after three series of injections at 10-day intervals. The levels of urinary protein, serum creatinine, and urea nitrogen in SHRs given AMNS and PS were elevated throughout the experiment and were significantly higher than these levels in other control groups on day 80. Histology in SHRs given AMNS and PS showed advanced FGS associated with glomerular hypertrophy and widespread interstitial fibrosis. Most small arteries and arterioles showed "onion peel" thickening and fibrinoid necrosis of the intima, which is characteristic of malignant arteriosclerosis. We observed that the gradient of glomerulosclerosis increased from superficial to deep cortical zones; this phenomenon had often been reported in human FGS. However, these distinguished lesions were not found in control groups. Therefore, it is suggested that systemic hypertension is one of the deleterious factors enhancing histologic and functional deterioration in FGS.
为研究高血压对局灶性肾小球硬化（FGS）进展的影响，我们通过联合给予嘌呤霉素氨基核苷（AMNS）和硫酸鱼精蛋白（PS），在自发性高血压大鼠（SHRs）中建立了FGS实验模型。将SHRs和作为对照品系的正常血压Wistar Kyoto大鼠每日皮下注射AMNS（1mg/100g体重）并静脉注射PS（分两次给予，每次2.5mg/100mg体重），持续4天；在每隔10天进行三轮注射后的第80天处死大鼠。给予AMNS和PS的SHRs的尿蛋白、血清肌酐和尿素氮水平在整个实验过程中均升高，且在第80天显著高于其他对照组的这些水平。给予AMNS和PS的SHRs的组织学检查显示存在进展性FGS，伴有肾小球肥大和广泛的间质纤维化。大多数小动脉和微动脉显示出“洋葱皮样”增厚以及内膜的纤维蛋白样坏死，这是恶性动脉硬化的特征。我们观察到肾小球硬化的梯度从浅表皮质区向深部皮质区增加；这种现象在人类FGS中经常有报道。然而，在对照组中未发现这些明显的病变。因此，提示全身性高血压是加剧FGS组织学和功能恶化的有害因素之一。
