Li Y, Mei Q B, Cho C H
Department of Pharmacology, Faculty of Medicine, University of Hong Kong, Hong Kong.
Chin Med J (Engl). 1998 Jan;111(1):12-6.
To investigate whether or not heparin can accelerate the healing process of acetic acid-induced gastric ulcers in rats and to identify the mechanisms for heparin to produce this effect, so that we can develop a new therapeutic application to heparin besides its traditional anticoagulant activity.
Male Sprague-Dawley rats were used to produce acetic acid-induced gastric ulcers. Heparin in the doses of 100, 500, and 1000 U/kg were administered intravenously through the tail vein once daily, starting 1 day after ulcer induction for 7 days in the dose-response experiment or heparin 1000 U/kg at a time schedule of 3, 5, and 7 days in the time-response study, respectively. The gastric mucosal blood flow (GMBF) was measured using a laser Doppler flowmeter under ether anesthesia. The rats were then sacrificed and the ulcer areas were measured. The gastric mucosa was then scraped for the determinations of mucosal prostaglandin E2 (PGE2) level and myeloper-oxidase (MPO) activity.
Heparin in the doses of 500 and 1000 U/kg accelerated the healing of acetic acid ulcers in a dose-dependent manner. The highest dose of heparin also reduced the ulcer areas in a time-dependent fashion. The effect was accompanied by an increase in gastric mucosal PGE2 levels. The same dose of heparin not only decreased the gastric mucosal MPO activity but also increased the GMBF in a time-related manner.
Heparin with the doses used in the present study accelerated the healing of acetic acid-induced gastric ulcers in rats in a dose- and time-dependent manner, and this action was related to its effects to increase the levels of gastric mucosal PGE2 and GMBF as well as to decrease the gastric mucosal MPO activity.
研究肝素是否能加速大鼠乙酸诱导型胃溃疡的愈合过程，并确定肝素产生这种作用的机制，以便我们能开发出肝素除传统抗凝活性之外的新治疗应用。
使用雄性斯普拉格-道利大鼠制作乙酸诱导型胃溃疡。在剂量反应实验中，从溃疡诱导后第1天开始，通过尾静脉每天静脉注射100、500和1000 U/kg剂量的肝素，持续7天；在时间反应研究中，分别在第3、5和7天以1000 U/kg的剂量注射肝素。在乙醚麻醉下，使用激光多普勒血流仪测量胃黏膜血流量（GMBF）。然后处死大鼠并测量溃疡面积。接着刮取胃黏膜以测定黏膜前列腺素E2（PGE2）水平和髓过氧化物酶（MPO）活性。
500和1000 U/kg剂量的肝素以剂量依赖性方式加速了乙酸溃疡的愈合。肝素的最高剂量也以时间依赖性方式减小了溃疡面积。该作用伴随着胃黏膜PGE2水平的升高。相同剂量的肝素不仅降低了胃黏膜MPO活性，还以时间相关的方式增加了GMBF。
本研究中使用的剂量的肝素以剂量和时间依赖性方式加速了大鼠乙酸诱导型胃溃疡的愈合，并且这种作用与其增加胃黏膜PGE2和GMBF水平以及降低胃黏膜MPO活性的作用有关。
