Cadranel J F, Dumont M, Mesa V, Degott C, Taillandier J, Erlinger S
Unité de Recherches de Physiopathologie Hépatique, INSERM U 24, Clichy.
Gastroenterol Clin Biol. 1989 Oct;13(10):779-82.
The effect of therapeutic doses of cyclosporine A (CyA) on bile flow and bile salt output was studied in the rat. Thirty male Sprague-Dawley rats (250 to 380 g) were injected intraperitoneally with CyA (n = 15) or vehicle (n = 15) at the dose of 10 mg.kg-1 for 3 weeks. The effect of CyA on basal and taurocholate-induced bile flow, on basal bile salt output and bile salt output under taurocholate infusion, and the effect of chronic administration of CyA on bile salt-independent bile flow was evaluated. Administration of CyA was associated with a decrease in basal bile flow (5.6 +/- 0.7 vs 6.7 +/- 0.7 microliters.min-1.100 g-1; p less than 0.001) and bile flow under taurocholate infusion (8.0 +/- 0.8 vs 10.9 +/- 1.1 microliters.min-1.100 g-1; p less than 0.001). Basal bile salt output (133.9 +/- 48.2 vs 173.8 +/- 53.6 nmol.min-1.100 g-1; p less than 0.003) and bile salt output under the infusion of taurocholate were significantly lower in cyclosporine-treated rats than in controls (443.3 +/- 48.2 vs 617.2 +/- 172.7 nmol.min-1.100 g-1; p less than 0.001). There was no significant difference in bile salt-independent bile flow between the 2 groups. There was no modification of seric alanine aminotransferase activity or hepatic histology. This study confirms that chronic administration of CyA at therapeutic doses can induce cholestasis. Cholestasis is related mainly to a decrease in bile salt secretion and bile salt-dependent flow.
研究了治疗剂量的环孢素A（CyA）对大鼠胆汁流量和胆盐输出的影响。将30只雄性Sprague-Dawley大鼠（250至380克）以10毫克·千克⁻¹的剂量腹腔注射CyA（n = 15）或赋形剂（n = 15），持续3周。评估了CyA对基础和牛磺胆酸盐诱导的胆汁流量、基础胆盐输出以及牛磺胆酸盐输注下胆盐输出的影响，以及长期给予CyA对不依赖胆盐的胆汁流量的影响。给予CyA与基础胆汁流量降低（5.6±0.7对6.7±0.7微升·分钟⁻¹·100克⁻¹；p＜0.001）和牛磺胆酸盐输注下的胆汁流量降低（8.0±0.8对10.9±1.1微升·分钟⁻¹·100克⁻¹；p＜0.001）相关。环孢素治疗组大鼠的基础胆盐输出（133.9±48.2对173.8±53.6纳摩尔·分钟⁻¹·100克⁻¹；p＜0.003）和牛磺胆酸盐输注下的胆盐输出显著低于对照组（443.3±48.2对617.2±172.7纳摩尔·分钟⁻¹·100克⁻¹；p＜0.001）。两组之间不依赖胆盐的胆汁流量没有显著差异。血清丙氨酸氨基转移酶活性或肝脏组织学没有改变。本研究证实，治疗剂量的CyA长期给药可诱导胆汁淤积。胆汁淤积主要与胆盐分泌减少和依赖胆盐的流量降低有关。
