氯苯丁酯引起大鼠肝肿大与肝细胞生长因子产生的可能关系

The possible relationship between hepatomegaly and releaseof plasma HGF level induced by clofibrate in rats.

目的研究氯苯丁酯引起的大鼠肝脏肿大与血浆中ＨＧＦ水平变化的关系。方法氯苯丁酯（５００，４００，３００，１００ｍｇ·ｋｇ－１·ｄ－１）加入饲料中喂养大鼠，在不同时间处死大鼠，取出肝脏称重和制备血清，以原代培养大鼠肝细胞ＤＮＡ合成检测ＨＧＦ的生物学活性。结果氯苯丁酯处理后的大鼠血清能显著增加原代培养大鼠肝细胞３Ｈ－ＴｄＲ的参入，ｃｐｍ值随着血清被稀释而逐渐降低，但仍高于对照组。大鼠血清中ＨＧＦ的释放在给药后４ｄ达到最高水平，为正常对照组的６倍以上，给药２ｗｋ后仍维持在正常水平的２倍以上。而氯苯丁酯引起肝脏肿大发生在给药２ｗｋ后，并维持在正常水平的１．８倍以上。

AIM To study the relationship between hepatomegaly and change of plasma HGF level induced by clofibrate in rats. METHODS Clofibrate at the dose of 500, 400, 300, 100 mg·kg-1·d-1 was added into the food for the animals. The rats were killed at different time intervals and the activities of HGF on the proliferation of the primary culture of rat hepatocytes were estimated. RESULTS The serum of rats pretreated by clofibrate could markedly increase the incorporation of 3HTdR into the normal control cells. The cpm value of the experimental group decreased with the dilution of the serum, but was still higher than that of the control group. After administration of clofibrate, the release of HGF into the rat plasma increased to the maximum at the 4th day, and maintained over 2fold of the normal level 2 wk after drug administration. Hepatomegaly induced by clofibrate happened about 2 wk after drug treatment and maintained at a level of 18fold of the normal liver. CONCLUSION Our results suggest that the hepatomegaly induced by clofibrate may be caused partly by the proliferative action of HGF on liver.