Foitzik T, Hotz H G, Hot B, Kirchengast M, Buhr H J
Department of Surgery, Benjamin Franklin Medical Center, Freie Universität Berlin, Germany.
J Gastrointest Surg. 1998 Jul-Aug;2(4):379-84. doi: 10.1016/s1091-255x(98)80078-4.
Increased plasma endothelin-1 (ET-1) levels in rats after alcohol administration and increased endothelin receptor expression in the pancreas in chronic alcoholic pancreatitis have led to the hypothesis that ET-1 may play a critical role in the pathogenesis of ethanol-induced pancreatic injury through impairment of perfusion. To further test the hypothesis that ET-1 mediates an alcohol-induced reduction of pancreatic perfusion, the present study compares the effect of intravenous alcohol and ET-1 on pancreatic capillary blood flow (PCBF) and investigates whether endothelin receptor blockade prevents the alcohol-induced reduction in PCBF. Anesthetized rats were randomly assigned to receive one of the following: a 1-hour infusion of 2 g/kg alcohol or the volume equivalent of saline solution plus ET-1 (1.25 microgram/kg), a specific endothelin-A receptor antagonist (50 mg/kg), or saline solution (volume equivalent). The pancreas was exposed for intravital microscopy; PCBF was determined at the same location before the test solutions were given, after the infusion, and 1 hour thereafter. Alcohol and ET-1 significantly decreased PCBF from 2.0 nl/min/cap to 1.7 nl/min/cap. The reduction in PCBF was even more pronounced when alcohol and ET-1 were combined (1.5 nl/min/cap), whereas the ET receptor antagonist increased PCBF in saline-treated rats to 2.2 nl/min cap and maintained stable PCBF in alcohol-treated animals. The observation that PCBF is reduced by both alcohol and ET-1 and that the alcohol-induced reduction of PCBF can be aggravated by ET-1 and prevented by a specific endothelin-1 antagonist supports the hypothesis that ET-1 is the mediator of the alcohol-associated reduction of pancreatic perfusion.
酒精给药后大鼠血浆内皮素-1（ET-1）水平升高，以及慢性酒精性胰腺炎患者胰腺中内皮素受体表达增加，这使得人们提出一种假说，即ET-1可能通过损害灌注在乙醇诱导的胰腺损伤发病机制中起关键作用。为了进一步验证ET-1介导酒精诱导的胰腺灌注减少这一假说，本研究比较了静脉注射酒精和ET-1对胰腺毛细血管血流量（PCBF）的影响，并研究内皮素受体阻断是否能预防酒精诱导的PCBF减少。将麻醉的大鼠随机分为以下几组：接受2 g/kg酒精1小时输注，或等量生理盐水加ET-1（1.25微克/千克）、特异性内皮素-A受体拮抗剂（50毫克/千克）或生理盐水（等量体积）。暴露胰腺进行活体显微镜检查；在给予测试溶液前、输注后及输注后1小时，在同一位置测定PCBF。酒精和ET-1均使PCBF从2.0 nl/分钟/毛细血管显著降至1.7 nl/分钟/毛细血管。当酒精和ET-1联合使用时，PCBF的降低更为明显（1.5 nl/分钟/毛细血管），而ET受体拮抗剂使生理盐水处理的大鼠PCBF增加至2.2 nl/分钟/毛细血管，并使酒精处理的动物PCBF保持稳定。PCBF在酒精和ET-1作用下均降低，且ET-1可加重酒精诱导的PCBF降低，而特异性内皮素-1拮抗剂可预防这种降低，这一观察结果支持了ET-1是酒精相关胰腺灌注减少的介质这一假说。
