Carnovale C E, Roma M G, Monti J A, Rodriguez Garay E A
Instituto de Fisiologia Experimental, Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Universidad Nacional de Rosario, Argentina.
Toxicology. 1991;68(3):207-15. doi: 10.1016/0300-483x(91)90070-h.
The main factors involved in the impairment of formation of the bile salt-independent bile flow (BSIF) in streptozotocin (SZ)-treated rats were examined. Twenty-four hours after SZ injection (50 mg/kg body wt, i.v.) bile flow, bile salt output and biliary excretion of the major inorganic electrolytes (sodium, chloride and bicarbonate) were significantly diminished. The relationship between bile flow and bile salt output obtained during the administration of sodium taurocholate at stepwise-increasing rates indicated that bile salt-independent bile flow (y-intercept) was diminished by 37% in SZ-treated rats. The relationship between electrolyte output and bile salt output showed that the fractions of sodium, chloride and bicarbonate excreted independently of bile salt (y-intercept) decreased to 59%, 47% and 67% of the control values respectively, while the amount of electrolyte secreted per unit of bile salt secreted was unaffected in SZ-treated rats. The hepatic activity of Na+,K(+)-adenosine triphosphatase (Na+,K(+)-ATPase) was decreased by 59% (P less than 0.05) in SZ-treated rats. Nicotinamide administered prior to SZ prevented the hyperglycemia indicative of SZ-induced diabetes, but had no effect on the decrease in Na+,K(+)-ATPase activity caused by the drug. These results suggest that SZ itself, and not its diabetogenic effect, decreases the BSIF by a mechanism that involves impairment of the biliary electrolyte excretion, which could be the result of the inhibition of the hepatic Na+,K(+)-ATPase activity.
研究了链脲佐菌素（SZ）处理的大鼠中，参与非胆盐依赖性胆汁流（BSIF）形成受损的主要因素。静脉注射链脲佐菌素（50mg/kg体重）24小时后，胆汁流量、胆盐输出以及主要无机电解质（钠、氯和碳酸氢盐）的胆汁排泄量均显著减少。以逐步增加的速率给予牛磺胆酸钠期间获得的胆汁流量与胆盐输出之间的关系表明，SZ处理的大鼠中非胆盐依赖性胆汁流（截距）减少了37%。电解质输出与胆盐输出之间的关系表明，独立于胆盐排泄的钠、氯和碳酸氢盐的比例（截距）分别降至对照值的59%、47%和67%，而SZ处理的大鼠中每分泌单位胆盐分泌的电解质分泌量未受影响。SZ处理的大鼠中Na +，K（+）-腺苷三磷酸酶（Na +，K（+）-ATPase）的肝脏活性降低了59%（P < 0.05）。在给予SZ之前给予烟酰胺可预防SZ诱导的糖尿病所指示的高血糖症，但对该药物引起的Na +，K（+）-ATPase活性降低没有影响。这些结果表明，SZ本身而非其致糖尿病作用，通过涉及胆汁电解质排泄受损的机制降低了BSIF，这可能是肝脏Na +，K（+）-ATPase活性受到抑制的结果。
