SERIAL MICROPUNCTURE ANALYSIS OF GLOMERULAR FUNCTION IN 2 RAT MODELS OF GLOMERULAR SCLEROSIS
SERIAL MICROPUNCTURE ANALYSIS OF GLOMERULAR FUNCTION IN 2 RAT MODELS OF GLOMERULAR SCLEROSIS
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DOI：
10.1172/jci113590
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发表时间：
1988-07-01
影响因子：
15.9
通讯作者：
ICHIKAWA, I
中科院分区：
文献类型：
--
作者：
FOGO, A;YOSHIDA, Y;ICHIKAWA, I
我们最近开发了一种微穿刺技术，以评估慢性肾脏疾病中相同肾单位的功能，并随后通过连续的薄作用组织学分析来检查其肾小球的形态。使用这种方法，早期功能模式和后期结构异常之间的潜在因果关系进行了检查，在肾小球的两个建立的大鼠模型肾小球硬化。方法：（a）单侧肾切除的Munich-Wistar大鼠，给予嘌呤霉素（PAN）;（B）阿霉素（ADM），连续8周（PAN大鼠）或31周（ADM大鼠），测定肾小球毛细血管液压（PGC）。在所有研究的动物中，PGC值保持在或略低于PAN或ADM给药前测量的水平。在PAN大鼠中，所有肾小球的SNGFR值进行性下降。尽管ADM大鼠中的一些肾小球的SNGFR增加高于在非肾切除对照大鼠中观察到的水平，但这些过度滤过的肾小球在研究完成时没有异常高的PGC，也没有表现出肾小球硬化。组织学分析显示，PAN组和ADM组在处死时评估的硬化程度和SNGFR之间存在显著的负相关性。在PAN大鼠中，长期给予血管紧张素I转换酶抑制剂captopril显著减弱了肾小球硬化的发展，而不影响早期PGC。在这些模型中的观察结果表明，肾小球高滤过和高血压不是肾脏疾病中肾小球硬化的发展所必需的，并且血管紧张素I转换酶抑制剂可以独立于其对肾小球毛细血管压力的影响而发挥其保护作用。
We have recently developed a micropuncture technique to assess repeatedly function of the same nephrons in chronic renal disease and subsequently examine the morphology of their glomeruli by serial thin-action histological analysis. Using this approach, a potential causal linkage between early functional patterns and late structural abnormalities was examined in glomeruli of two established rat models of glomerular sclerosis. The models are (a) puromycin aminonucleoside (PAN) administration in unilaterally nephrectomized Munich-Wistar rats and (b) adriamycin (ADM) treatment in nonnephrectomized glomerular capillary hydraulic pressure (PGC) were measured repeatedly for 8 (PAN rats) or 31 wk (ADM rats). In all animals studied, values for PGC remained at, or slightly below, levels measured before PAN or ADM administration. SNGFR values declined progressively in all glomeruli in PAN rats. Although some glomeruli in ADM rats had an increase in SNGFR above levels observed in nonnephrectomized control rats, these hyperfiltering glomeruli did not have abnormally high PGC nor did they exhibit glomerular sclerosis at the completion of the study. Histological analysis revealed the existence of a significant inverse correlation between the degree of sclerosis and SNGFR assessed at the time of sacrifice in both PAN and ADM groups. Chronic administration of captopril, an angiotensin I converting enzyme inhibitor, in PAN rats substantially attenuated development of glomerular sclerosis without affecting PGC in earlier stages. The observations in these models indicate that glomerular hyperfiltration and hypertension are not required for the development of glomerular sclerosis in renal diseases, and angiotensin I converting enzyme inhibitor can exert its protective effect independently of its effect on glomerular capillary pressure.