急性脑出血致脑源性多器官功能障碍综合征模型IL-1β的基因表达及与血清内毒素的相关性研究

山东大学学报(医学版)

急性脑出血致脑源性多器官功能障碍综合征模型IL-1β的基因表达及与血清内毒素的相关性研究

屈传强¹, 麻琳², 郭洪志², 贺燕³, 王蕾³, 李春海¹

1. 山东大学齐鲁医院影像中心, 山东济南 250012；2. 山东大学齐鲁医院神经内科, 山东济南 250012； 3. 山东中医药大学第二附属医院神经内科

收稿日期:2006-09-27 修回日期:1900-01-01 出版日期:2007-04-24 发布日期:2007-04-24
通讯作者: 麻琳

Relationship between gene expression of IL-1β and serum endotoxin in a animal model of cerebrogenic multiple organ dysfunction syndrome complicated by cerebral hemorrhage

QU Chuan-qiang¹, MA Lin², GUO Hong-zhi², HE Yan³, WANG Lei³, LI Chun-hai¹

1. Department of Radiology, Qilu Hospital of Shandong University；2. Department of Neurology, Qilu Hospital of Shandong University；3.Department of Neurology, Second Hospital of Shandong University of Traditional Chinese Medicine

Received:2006-09-27 Revised:1900-01-01 Online:2007-04-24 Published:2007-04-24
Contact: MA Lin

摘要/Abstract

摘要： 目的：探讨急性脑出血致多器官功能障碍综合征（MODS）模型IL-1β的基因表达及与血清内毒素的相关性，分析脑源性多器官功能障碍综合征（CMODS）的发生机制。方法: 将96只Wistar大鼠按随机化原则分为16组：正常对照组6只；假手术组6只；实验1组和2组各42只，均分为4、8、12、24、36、48和72h时相点的7个亚组，每亚组6只。尾状核注入不同剂量的胶原酶建立大鼠急性脑出血模型；分别采用偶氮显色法鲎试验定量测定血清内毒素和原位杂交技术测定肺、肝、肠和肾组织IL-1βmRNA水平；使用CMIA真彩色医学图像分析系统，检测IL-1βmRNA的相对含量。结果:实验1、2组肺、肝、肠和肾组织IL-1βmRNA的表达自12h开始升高，24～36h达高峰，12～48h各器官组织与正常组和假手术组比较，差异均有统计学意义(P均＜0.01)；实验2组表达较实验1组增高，24h组各器官表达差异均有统计学意义（P＜0.01）；实验1组、2组血清内毒素含量与正常对照组及假手术组比较差异，亦有显著性(P＜0.01、P＜0.001)，且实验2组高于实验1组(P＜0.01)，血清内毒素于术后8?h开始升高， 24h达高峰，实验1组在72h时接近正常，而实验2组72h时仍维持较高水平；肺、肝、肠和肾组织中IL-1βmRNA的表达与血清内毒素均存在显著相关性。结论：急性脑出血致CMODS模型存在内毒素血症和炎性因子IL-1β在各脏器的异常表达，内毒素血症刺激炎性因子的异常释放，诱发全身炎症反应,导致MODS的发生。

Abstract: Objective: To discuss the relationship between gene expression of IL-1βand serum endotoxin in a animal model of cerebrogenic multiple organ dysfunction syndrome(CMODS) complicated by cerebral hemorrhage, and to investigate the pathogenesis of CMODS. Methods: Ninty-six Wistar rats were randomly divided into four groups: normal control group (n=6), sham-operative group (n=6) and model group 1 with 0.4U collagenase (n=42) and model group 2 with 0.8U collagenase cerebral (n=42). The content of endotoxin in plasma was evaluated with a test box. Gene expression of IL-1β was assayed using in situ hybridization. The area density and the optical density of positive staining expressing IL-1βmRNA were analyzed for the relative content of IL-1βmRNA using in situ hybridization and CMIA medical imaging analysis system. Results: Expression of IL-1βmRNA in lung, liver, intestines andkidney tissues started to increase at 12 hours in model groups, and reached the peak at 24-36 hours. This was markedly higher in model group 2 than in model group 1 at 24 hours(P＜0.01). Compared with normal control and shamoperative groups, expression of IL-1βmRNA was significantly higher at 12-48 hours in models groups(P＜0.01). There was endotoxemia administration after acute cerebral hemorrhage. Plasma endotoxin level of model group 2 was higher than that of model group 1(P＜0.01). It started to increase at 8 hours after hemorrhage andpeaked at 24 hours, then returned to the baseline value at 72 hours in model group 1, but still maintained high level in model group 2. Relative analysis indicated that there was significant positive correlation between the IL1βmRNA expression in lung, liver, kidney, intestine and plasma endotoxin level(P＜0.01). Conclusion: Endotoxemia occurres after cerebral hemorrhage, and the gene expression of IL-1βincreases, which implicate that endotoxemia irritates the release of inflammatory factor, and systemic inflammatory response syndrom(SIRS) developes. This is key process in generation of CMODS.

Key words: Multiple organ failure, Endotoxins, Interleukin-1β, Gene expression, Rat, Wistar

中图分类号:

R743.34

屈传强,麻琳,郭洪志,贺燕,王蕾,李春海 . 急性脑出血致脑源性多器官功能障碍综合征模型IL-1β的基因表达及与血清内毒素的相关性研究[J]. 山东大学学报(医学版), 2007, 45(4): 353-356.

QU Chuan-qiang,MA Lin,GUO Hong-zhi,HE Yan,WANG Lei,LI Chun-hai. Relationship between gene expression of IL-1β and serum endotoxin in a animal model of cerebrogenic multiple organ dysfunction syndrome complicated by cerebral hemorrhage[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2007, 45(4): 353-356.

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