山莨菪碱对多器官功能障碍综合征保护机制的实验研究  

Experimental Study on the Preventive Mechanism of Anisodamine on Multiple Organ Dysfunction Syndrome

作　　者：尹文[1] 虎晓岷[1] 袁静[2] 杨剑虹[1] 张金山[3] 黄杨[1] 

机构地区：[1]第四军医大学西京医院急诊科,陕西西安710032 [2]解放军第五医院 [3]第四军医大学基础部组织胚胎教研室

出　　处：《中国医师杂志》2004年第1期8-10,共3页Journal of Chinese Physician

基　　金：国家自然科学基金资助项目 (30 0 0 0 1 65)

摘　　要：目的　探讨山莨菪碱 ( 65 4-2 )对多器官功能障碍综合征 (MODS)可能的治疗机制。方法　采用失血性休克合并内毒素刺激诱发MODS家兔模型 ,2 4只大耳白兔随机分为正常对照组 (C组 )、模型组 (M组 )、65 4-2治疗组 (T组 )。用原位杂交 (ISN)技术、凝胶电泳迁移率改变 (EMSA)及酶联免疫吸附试验 (ELISA)法分别检测肺泡巨噬细胞 (PAM )及肝枯否细胞 (KC)中I -кB激酶(IKK -β)mRNA表达、NF -кB的活性和细胞培养上清液中TNF -α的含量。并进行动脉血气、生化和内脏组织病理学光镜检查。 结果　M组和C组比较PAM和KC中IKK -βmRNA表达 [( 0 15± 0 0 3 ) ;( 0 17± 0 0 4) ] ,NF -кB活性 [( 1 49± 0 3 0 ) ;( 1 72± 0 3 6) ]和上清液TNF -α的含量 [( 2 79 74± 2 5 91) ;( 3 0 0 0 5± 3 0 86)ng/L]明显增高 ( P 均 <0 0 1)。肝肺肾小肠等脏器功能发生不同程度损害 ;65 4-2治疗组能显著抑制M组PAM和KC中IKK -βmRNA表达 [( 0 10± 0 0 2 ) ;( 0 11± 0 0 2 ) ]、NF -кB活性 [( 0 65±0 10 ) ;( 0 88± 0 2 0 ) ]和TNF -α[( 180 61± 13 0 1) ;( 2 10 2 8± 18 0 1)ng/L]的分泌 (P <0 0 1或P <0 0 5 )。明显缓解MODS动物内脏组织的功能损害。结论　 65 4-2通过抑制IKK -β/NFObjective To investigate the preventive mechanism of Anisodamine (654-2) on multiple organ dysfunction syndrome (MODS) of rabbits. Methods Rabbit model of MODS induced by hemorrhagic shock and endotoxin was used in this study. Twenty-four rabbits were randomly divided into the control group (C group) , hemorrhagic shock plus endotoxin group (M group) and 654-2 treatment group (T group). The expression of IKK-β of pulmonary alveolar macrophage (PAM) and kuffer cell(KC), the NF-κB activity of nuclear protein extracted from PAM and KC and the concentration of tumor necrosis factor-ɑ (TNF-ɑ) in the culture supernatant were measured by in situ hybridization (ISH), electrophoretic mobility shift assay (EMSA) and enzyme linked immune absorbent analysis(ELISA), respectively. Then the blood air, biochemical and pathological changes in visceral organs were examined in each groups. Results In PAM and KC of M group, The expression of IKK-β mRNA [(0 15±0 03);(0 17±0 04)], the activity of NF-κB [(1 49±0 30);(1 72±0 36)] and the secretion level of TNF-α [( 279 74±25 91);(300 05±30 86)ng/L] were significantly higher than those of control group (P<0 01), and the severity of organ damages in lung,liver and intestine significantly increased. 654-2 treatment can significantly inhibit the the expression of IKK-β [(0 10±0 02);(0 11±0 02)] and activity of NF-κB [(0 65±0 10);(0 88±0 20)], decrease the secretion levels of TNF-ɑ [(180 61±13 01);(210 28±18 01)ng/L] in PAM and KC (P<0 01 or P<0 05), and relieve the injury severity of visceral tissues in MODS rabbits. Conclusions 654-2 shows treatment effect on development and progression of MODS induceed by hemorrhagic shock and endotoxin, which is closely related to regulatory role of 654-2 on IKK-β/NF-κB/TNF-α activity.

关 键 词：山莨菪碱 多器官功能障碍综合征 作用机制 实验研究 失血性休克 内毒素 IKK一β NF-KB TNF-α 

分 类 号：R969[医药卫生—药理学]