Abstract
Unilateral progressive Masugi nephritis was produced in albino rabbits weighing 2.0 to 2.5 kg, according to the method of Sarre and Wirtz modified by Nagasawa. The following four experimental groups were designed. 1) Heparin group (14 rabbits); heparin, 1000 units/kg, twice a day, S. C. was started simultaneously with nephrotoxic serum (NTS) injection, and was given for 3 weeks. 2) Urokinase group (14); this, 1800 units/kg, twice a day, I. V. was started 5 days after NTS and was continued until the sacrifice. 3) Ancrod group (13); this was started 5 days after NTS, and was given, initially, 0.5 units/kg, I.V., and 1 unit/kg, one hour apart, then from the next day, 1 unit/kg, twice a day. 4) Control group (12); no treatment except for NTS. All animals were sacrificed 22 days after NTS. Evaluation was performed as follows. 1) Light microscopic examination is to count the number of glomeruli with circumferential crescent formation per 100 glomeruli. 2) by immunofluorescence using FITC-guinea pig anti-rabbit fibrinogen serum, the degree and number of fluorescent glomeruli were examined per 50 glomeruli. 3) by microangiography according to the method of L junggvist, the number of glomeruli visualized over a certain area of the cortex was calculated. In the control group, the incidence of crescent formation was 59.5±9.0 (SE), while it was 31.9±9.5 (p<0.05) in heparin group, 30.3±8.1 (p<0.02) in urokinase group and 14.8±5.7 (p<0.01) in ancrod group. But, 2 of 13 rabbits given ancrod showed glomerular mesangiolytic injury, known to occur in poisoning by the Habu snake venom. The immunofluorescent studies disclosed a significant increase in the number of negatively stained glomeruli from 3 treated groups. Moreover, the numbers of glomeruli seen per unit of cortex by microangiography in the control, heparin, urokinase and ancrod groups were 70.2±6.5, 104.3±6.0 (p<0.001), 99.0±7.4 (p<0.01), 102.4±7.2 (p<0.01), respectively. The present result demonstrates that three kinds of agents including ancrod are equally effective in spite of different mechanisms of action for attenuation of intraglomerular coagulation induced by the experimental nephritis. But, the mesangiolytic injuly observed in a few rabbits given ancrod suggests its need to be more purified for future clinical use.
