脑出血致多器官功能障碍综合征动物模型的建立及其发病机制的研究

Establishment of a model of multiple organ dysfunction syndrome by cerebral hemorrhage in rats and research of the mechanism

目的 构建脑出血致多器官功能障碍综合征(MODS)的动物模型,并初步探讨其发病机制。方法 Wistar大鼠54只,随机分为正常对照组(6只)、假手术组(6只)及出血后7个亚组(4、8、12、24、36、48和72 h组,每组6只);向大鼠尾状核内注射Ⅶ型胶原酶0.8 U建立脑出血模型,向假手术组大鼠注射同体积的等渗盐水,检测出血后各时相点血浆内毒素、肝功能、肾功能、心肌酶及各脏器组织的病理变化,依据诊断标准判断全身炎性反应综合征、MODS的发生率。 结果 (1)出血8 h组大鼠血浆内毒素为(0.43±0.10)EU／ml较正常对照组(0.18±0.02)EU／ml、似手术组的(0.18±0.03)EU／ml大鼠明显升高(P<0.05),在24-36 h达高峰,48 h后下降。出血12 h组大鼠天冬氨酸氨基转移酶(197±20)u／L、丙氨酸氨基转移酶(227±32)U／L、尿素氮(17.5±2.1)mmol／L、肌酐(47.5±5.0)umol／L、肌酸肌酶(2 147±277)U／L、乳酸脱氢酶(648±65)U／L明显升高(P<0.05),在24-36 h达高峰,48 h后下降。(2)大鼠脑出血后各时相点的脏器组织均有不同程度的炎性损害,在24-48 h的脏器病理变化达到高峰,在72 h仍可见炎性损害。(3)大鼠脑出血后全身炎性反应综合征(SIRS)发生率为100％,MODS发生率为67.9％。 结论 (1)以0.8 U胶原酶注入大鼠尾状核为诱发因素。

Objective To establish the model of multiple organ dysfunction syndrome (MODS)caused by cerebral hemorrhage and to investigate the mechanism. Methods 54 Wistar rats were randomly divided into 3 groups: normal group(n=6), sham-operative group(n = 6) and hemorrhage groups( n = 42) which including at 4h、8h、12h、24h、36h、48h、72h seven time points after bleeding. Cerebral hemorrhage was induced in rats by injecting 0. 8U collagenase VII into the caudase putamen. The consistency of plasma endotpxin was assayed, biochemical criterions and the pathological changes were examined. The incidences of systemic inflammatory response syndrome (SIRS) and MODS was recommended according to diagnostic criteria. Results (1)The consistency of plasma endotoxin was significantly higher than the control criterions after the 8 h per time median (0.43?.10)EU/ml vs(0.18?.02)EU/ml、(0. 18 ?. 03) EU/ml; P<0.05, peaked at 24 - 16 h and decreased after 48h. The biochemical criterions were significantly higher than the control criterions ( P < 0. 05) after the 12 h per time, peaked at 24-36 h and decreased after 48 h. (2) Organs at each time point were observed inflammatory injuries in different degrees after Cerebral hemorrhage, The injuries peaked at the 24 -48 h, which could be observed already at the 72 h per time. (3) Incidences of SIRS and MODS were respectively 100% and 67.9% after cerebral hemorrhage. Conclusion (1) An experimental animal model of MODS can be established successfully by cerebral hemorrhage which can be induced in rats by injecting 0. 8 U collagenase into the caudate putamen. (2) Pathological changes of intestinal mucosa and hepatic tissues can provide morphologic basis foroccurrence of endotoxemia after cerebral hemorrhage. (3) Endotoxemia may contribute to occurrence of MOFS by cerebral hemorrhage.