Hattori T, Ito M, Nagamatsu T, Suzuki Y
Department of Pharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
Jpn J Pharmacol. 1990 Jan;52(1):131-40. doi: 10.1254/jjp.52.131.
We investigated the antinephritic effects of TJ-8014, in comparison to dipyridamole, on crescentic-type anti-GBM nephritis in rats. When administration of test drugs was started from the heterologous phase (from the day after the anti-GBM serum injection), TJ-8014 at 2.0 g/kg/day, p.o., markedly inhibited the urinary protein excretion and elevations of plasma cholesterol and urea nitrogen levels as well as glomerular histopathological changes (i.e., crescent formation, adhesion and fibrinoid necrosis) throughout the 40-day observation period. TJ-8014 at 0.1 and 0.5 g/kg/day, p.o., and dipyridamole at 0.4 g/day, p.o., inhibited only the histopathological changes. When treatment was started from the autologous phase (from the 22nd day after the anti-GBM serum injection) after the disease had been established, only the high dose of 5.0 g/kg/day of TJ-8014, p.o., was effective in improving the histopathological changes of the established nephritis, as assessed on the 53rd day. The low doses of TJ-8014 and dipyridamole were ineffective. These results suggest that TJ-8014 may be a useful Japanese herbal medicine against rapidly progressive glomerulonephritis, which is characterized by severe glomerular lesions with the extensive formation of crescents. Furthermore, the mechanisms of action of this medicine will be discussed.
我们研究了TJ - 8014与双嘧达莫相比，对大鼠新月体型抗肾小球基底膜（GBM）肾炎的抗肾炎作用。当从异源期（抗GBM血清注射后第二天）开始给予受试药物时，口服2.0 g/kg/天的TJ - 8014在整个40天的观察期内显著抑制尿蛋白排泄、血浆胆固醇和尿素氮水平的升高以及肾小球组织病理学变化（即新月体形成、粘连和纤维蛋白样坏死）。口服0.1和0.5 g/kg/天的TJ - 8014以及口服0.4 g/天的双嘧达莫仅抑制组织病理学变化。当在疾病确立后从自身期（抗GBM血清注射后第22天）开始治疗时，在第53天评估发现，仅口服5.0 g/kg/天的高剂量TJ - 8014对改善已确立肾炎的组织病理学变化有效。低剂量的TJ - 8014和双嘧达莫无效。这些结果表明，TJ - 8014可能是一种有效的日本草药，可用于治疗以严重肾小球病变伴广泛新月体形成为特征的快速进行性肾小球肾炎。此外，还将讨论这种药物的作用机制。
