Study on Correlation Between Aminonucleoside Induced Experimental Focal Glomerular Sclerosis and Mesangial Dysfunction in Rats

To clarify the pathogenesis of focal glomerular sclerosis (FGS), aminonucleoside (AN) induced animal model of rat FGS was studied through two kinds of experimental procedures. In experiment I, AN (0.5mg per 100g body weight) was daily administrated subcutaneously to rats for 30 days. Furthermore, periodic unilateral nephrectomy and successive sacrifice of each animal was done from the 4 th to 88 th experimental day. Conventional light microscopic (LM) and immu nofluorescent (IF) studies for rat IgG, IgM and C3 of kidneys were done. Although full blown FGS picture was first seen in the rat kidney sacrificed in the 69 th day, earlier cases also revealed light microscopically considerable expansion and PAS positive deposits of the mesangial areas. IF studies showed rat IgG, IgM and C3 depositions predominantly in the mesangial areas, furthermore, intensity of their staining was gradually increased in the later obtained kidneys. It seemed that the depositions of these serum protein components always preceded to the occurrence of the segmental sclerosis of capillary tufts. In experiment II, besides 30 days daily AN administration, aggregated human γ-globulin (AH γ-gl) was injected to groups of rats at the 40 th, 60 th, 80 th and 100 th experimental day. Each group, consisting of 3 to 4 rats, was sacrificed periodically up to 5 days. IF study for human IgG was done besides conventional LM and IF studies. In results, the tendency of increased uptake and delayed disappearance of AH γ-gl in the mesangial areas was noted in AN administrated rats of later sacri ficed groups. Otherwise, the LM and IF studies were just in accordance with those of experiment I. From the hitherto described evidences, it was concluded that increased local accumulation of auto-logous serum protein components in the mesangial areas due to dysfunction of mesangial transport observed in nephrotic rat kidney may be important factor to produce focal sclerosis of capillary tufts leading to FGS through local ischemia and fibrosis.