克仑特罗对大鼠肝细胞氮代谢及6-磷酸葡萄糖脱氢酶活性的影响

EFFECTS OF CLENBUTEROL ON NITROGEN METABOLISM AND G6PDH ACTIVITY OF RAT HEPATOCYTE

目的 探讨克仑特罗 (Cl)调节大鼠肝细胞物质代谢及药理学机制。方法 测定Cl( 1× 10 - 6 mol·L- 1 )对大鼠原代肝细胞培养液尿素氮水平以及肝细胞3H 亮氨酸参入 ,胰岛素样生长因子I(IGF I)水平和 6 磷酸葡萄糖脱氢酶 (G6PDH)活性的影响。结果 Cl使培养液尿素氮浓度下降 2 5 5 1% (P <0 0 5 ) ;使肝细胞3H 亮氨酸参入量增加2 3 3 5 % (P <0 0 5 ) ;增加肝细胞产生IGF I的趋势 (P >0 0 5 ) ;使肝细胞G6PDH活性下降 4 5 2 2 % (P <0 0 5 )。β受体阻滞剂普萘洛尔 (Pro)对Cl的上述作用均有阻断作用。结论 Cl可增强大鼠肝细胞氮素保留和蛋白质合成 ,以及抑制肝细胞G6PDH活性而具有调节机体物质代谢的药理学效应。

AIM To study the effects of β 2 adrenergic receptor selective agonist clenbuterol on nitrogen metabolism and glucose 6 phosphate dehydrogenase activity of rat hepatocyte and its pharmacological mechanism. METHODS Biochemical methods were used to study the influence of clenbuterol on urea nitrogen concentration of hepatocyte culture medium, 3H leucine incorporation into hepatocyte,insulin like growth factor I (IGF I) production and glucose 6 phosphate dehydrogenase (G6PDH) activity of rat hepatocyte. RESULTS The results showed that urea nitrogen production by cultured rat hepatocytes was markedly affected with clenbuterol treatment (1×10 -6 mol·L -1 ), urea nitrogen concentration of culture medium was decreased by 25 51% ( P <0 05) compared with control. The inhibitory effect of hepatocyte urea nitrogen production of clenbuterol was blocked by propranolol, a β adrenoreceptor antagonist (1×10 -6 mol·L -1 ), but hepatocyte urea nitrogen level was not affected with propranolol treatment only ( P >0 05). The content of 3H leucine incorporation in rat hepatocyte was significantly increased by 23 35% ( P <0 05) with clenbuterol treatment (1×10 -6 mol·L -1 ), and the enhanced effect of 3H leucine incorporation into hepatocyte was antagonized by propranolol (1×10 -6 mol·L -1 ). The level of 3H leucine incorporation of rat hepatocyte was not influenced by propranolol alone. IGF I production of rat hepatocyte might be affected by clenbuterol. IGF I concentration of culture medium was increased by 39 46% with clenbuterol (1×10 -6 mol·L -1 ), but no significant difference was found compared with the control ( P >0 05). Moreover, G6PDH activity of rat hepatocyte was significantly decreased by 43 36% ( P <0 05) with clenbuterol treatment (1×10 -6 mol·L -1 ), and the declined effect of clenbuterol was antagonized by propranolol. G6PDH activity of rat hepatocyte was not affected on condition that propranolol was administered alone ( P >0 05). CONCLUSION It is suggested that clenbuterol may regulate nitrogen and fat metabolism by means of increasing nitrogen retention and protein synthesis, and decreasing G6PDH activity of rat hepatocyte for pharmacological effects.