Sarin S K, Groszmann R J, Mosca P G, Rojkind M, Stadecker M J, Bhatnagar R, Reuben A, Dayal Y
Hepatic Hemodynamic Laboratory, Veterans Administration Medical Center, West Haven, Connecticut 06516.
J Clin Invest. 1991 Mar;87(3):1032-6. doi: 10.1172/JCI115062.
We investigated the role of early portal hypotensive pharmacotherapy in preventing the development of portal-systemic shunting in a portal hypertensive model of chronic murine schistosomiasis induced by infecting C3H mice with 60 cercariae of Schistosoma mansoni. Propranolol was administered in drinking water to 20 animals for a period of 6 wk at a dose of 10 mg.kg-1d-1, starting at 5 wk of schistosomal infection. 32 age-matched mice with chronic schistosomal infection served as controls. All animals were studied 11 wk after the infection. Compared with controls the portal pressure (10.8 +/- 0.40 mmHg) was significantly lower (P less than 0.001) in the propranolol-treated animals (7.9 +/- 0.80 mmHg). Portal-systemic shunting was decreased by 79%, from 12.2 +/- 3.34% in controls to 2.5 +/- 0.99% in the propranolol group (P less than 0.05). Portal venous inflow was reduced by 38% in the propranolol treated animals (2.50 +/- 0.73 ml/min; n = 6) compared with controls (4.00 +/- 0.34 ml/min; n = 8; P less than 0.05). The worm burden, the granulomatous reaction, the collagen content of the liver, and the serum bile acid levels were not significantly different between the two groups of animals. These results demonstrate that in chronic liver disease induced by schistosomiasis, the development of portal-systemic shunting can be decreased or prevented by the reduction of flow and pressure in the portal system.
我们研究了早期门脉高压药物治疗在预防慢性小鼠血吸虫病门脉高压模型中门体分流形成中的作用。该模型通过给C3H小鼠感染60条曼氏血吸虫尾蚴诱导而成。从血吸虫感染第5周开始,对20只动物在饮水中给予普萘洛尔,剂量为10mg·kg-1·d-1,持续6周。32只年龄匹配的慢性血吸虫感染小鼠作为对照。所有动物在感染后11周进行研究。与对照组相比,普萘洛尔治疗组动物的门脉压力(7.9±0.80mmHg)显著降低(P<0.001),对照组为(10.8±0.40mmHg)。门体分流减少了79%,从对照组的12.2±3.34%降至普萘洛尔组的2.5±0.99%(P<0.05)。与对照组(4.00±0.34ml/min;n=8)相比,普萘洛尔治疗组动物的门静脉流入量减少了38%(2.50±0.73ml/min;n=6;P<0.05)。两组动物之间的虫负荷、肉芽肿反应、肝脏胶原含量和血清胆汁酸水平无显著差异。这些结果表明,在血吸虫病诱发的慢性肝病中,门体分流的形成可通过降低门脉系统的血流和压力而减少或预防。