Solomon H, Contis J, Li A P, Kaminski D L
Department of Surgery, St Louis University School of Medicine, MO 63110, USA.
Prostaglandins Leukot Essent Fatty Acids. 1996 Apr;54(4):265-71. doi: 10.1016/s0952-3278(96)90057-5.
Bile flow rates and composition are subject to a wide variety of neural, endocrine and paracrine influences. The effects of these multiple factors may be different in the diseased liver compared to the response produced in the normal liver. As prostanoids may have a therapeutic role in liver disease it was intended to evaluate the effects of two principal therapeutic prostanoids, prostaglandin E2 and prostacyclin, on bile flow in dogs with a normal liver and in dogs with hepatotoxin-induced liver injury. Initially, in awake animals with chronic biliary and gastric fistulas the bile flow response to prostaglandin E2 and prostacyclin was evaluated and compared to the response produced by bile salt infusion alone and to that produced by the standard choleretic hormones, secretin and glucagon. The animals were then fed alpha-naphthylisothiocyanate (ANIT) and the studies repeated. ANIT is a hepatoxin that produces bile duct cell hyperplasia which was confirmed in dogs by demonstrating that ANIT increased [3H]thymidine incorporation by isolated canine bile duct cells. In normal dogs, the prostanoids, secretin, and glucagon increased hepatic bile flow. 10 days of ANIT feeding produced a hypercholeresis. While secretin was able to stimulate the hyperplastic biliary epithelium and increase bile flow over values produced by the hyperplastic biliary epithelium alone, neither prostaglandin E2, prostacyclin, or glucagon appeared to stimulate the hyperplastic biliary epithelium. As ANIT produced evidence of cholestasis and hepatocellular damage, only secretin would seem to have a potential therapeutic role in increasing bile flow in cholestatic liver disorders associated with bile duct cell hyperplasia.
胆汁流速和成分受到多种神经、内分泌和旁分泌因素的影响。与正常肝脏产生的反应相比，这些多种因素在患病肝脏中的作用可能有所不同。由于前列腺素可能在肝脏疾病中具有治疗作用，因此旨在评估两种主要的治疗性前列腺素，即前列腺素E2和前列环素，对正常肝脏犬和肝毒素诱导的肝损伤犬胆汁流动的影响。最初，在患有慢性胆管和胃瘘的清醒动物中，评估了对前列腺素E2和前列环素的胆汁流动反应，并将其与单独输注胆盐产生的反应以及标准利胆激素促胰液素和胰高血糖素产生的反应进行比较。然后给动物喂食α-萘基异硫氰酸盐（ANIT）并重复这些研究。ANIT是一种肝毒素，可导致胆管细胞增生，通过证明ANIT增加分离的犬胆管细胞的[3H]胸苷掺入量，在犬中得到证实。在正常犬中，前列腺素、促胰液素和胰高血糖素可增加肝胆汁流量。喂食ANIT 10天会产生胆汁分泌过多。虽然促胰液素能够刺激增生的胆管上皮并使胆汁流量增加，超过仅由增生的胆管上皮产生的值，但前列腺素E2、前列环素或胰高血糖素似乎均未刺激增生的胆管上皮。由于ANIT产生了胆汁淤积和肝细胞损伤的证据，因此似乎只有促胰液素在增加与胆管细胞增生相关的胆汁淤积性肝病胆汁流量方面具有潜在的治疗作用。
