阿加曲班对大鼠脑出血模型脑水肿作用的研究

Study of argatroban's effect on brain edema in rat model of intracerebral hemorrhage

目的探讨阿加曲班对大鼠脑出血模型脑水肿的作用。方法取雄性SD大鼠40只,体重300～350g,随机分为A、B、C、D、E组,每组8只。大鼠用10%水合氯醛(350mg/kg)腹腔注射麻醉后,经立体定向分别向右侧尾状核区注入生理盐水60μl、无肝素自体血50μl+生理盐水10μl、无肝素自体血50μl+Argatroban生理盐水溶液(0.5μg/ml)10μl、含10U凝血酶生理盐水溶液50μl+生理盐水10μl、含10U凝血酶生理盐水溶液50μl+Ar-gatroban生理盐水溶液(0.5μg/ml)10μl。48h后,断头处死,测定脑含水量,HE染色,观察脑组织病理学变化。结果C、E两组脑组织含水量降低,与B、D两组比较有明显差别(P<0.05);B组与D组比较脑组织含水量无明显差别(P>0.05)。HE染色观察:B组可见血肿周围脑组织水肿,炎症细胞渗出,脑组织疏松,神经细胞呈气球样变、坏死;D组可见注射部位脑组织水肿,脑组织疏松,炎症细胞渗出;C、E两组上述改变减轻;A组未见血肿及局部明显病理学改变。结论阿加曲班可减轻凝血酶造成的脑水肿;

Objective To investigate argatroban＇ s effect on brain edema in rats after intracerebral hemorrhage. Methods A total of 40 male Sprague-Dawley rats, weighing 300 to 350g, were used for experiments. Animals were divided into 5 groups randomly, A, B, C, D, and E ,8 in each group. The animals were anesthetized with an intraperitoneal injection of 10% chlorali hydras（350mg/kg）. After a needle was inserted stereotaxically into the right caudate nucleus of the rats, the animals received an infusion of 60μl saline,50μl autologous whole blood ＋ 10μl saline,50μl autologous whole blood ＋ 10μl argatroban solution ,50μl thrombin solution ＋ 10μl saline ,50μl thrombin solution ＋ 10μl argatroban solution respectively. After 48h,the rats were decapitated for brain water content measurement and Hematoxylin and eosin staining was performed to examine brain histological changes. Results In C and E groups, the brain water content was significantly decreased, and were significantly different from that of groups B, D （ P 〈 0.05 ）. There were no significant differentence between group B and D（P 〉 0.05 ）. HE staining and observing by Light-microscope showed that in the rats of B group, the brain edema and neural injury surrouding the hematoma could been observed, inflammatory cells transmigrated, the nervous tissues were loose, the cell ballooning degeneration and necrosis could been observed. In D group, the brain tissues swelled and were loose around the injected area, inflammatory cells transmigrated, the changes of C and E groups were slighter. There were not obviously pathological changes in A group. Conclusion Argatroban relieves the brain edema caused by the thrombin. Argatroban diminishes perihematomal cerebral edema in the rats after intracerebral hemorrhage.