【作者】 袁兆新；

【导师】 孙连坤；

【作者基本信息】 吉林大学 ， 病理学与病理生理学， 2005， 硕士

【摘要】 参麦注射液是以人参、麦冬为主要成分配制而成,可治疗和辅助治疗多种疾病。本文研究了参麦注射液的抗休克作用及对IκBα和TLR4 基因表达的影响。实验利用大鼠建立了体内内毒素休克模型与“双重打击”休克模型(失血性休克+内毒素),通过观察大鼠脾脏中NF-κB 信号转导途径中TLR4 和IκBα基因表达水平及肺脏组织TNF-α含量、肺脏组织的形态学变化来探讨参麦的抗休克效果及其作用机制。结果发现大鼠在内毒素处理及双重打击(失血性休克+内毒素)作用下TLR4 的表达增高、IκBα的表达降低。而当给与参麦注射液时能够降低TLR4 的表达、增加IκBα的表达,同时抑制促炎介质TNF-α的释放。透射电镜下观察参麦注射液对失血及内毒素引起的大鼠肺组织损害具有明显的保护作用。其主要机制是通过抑制NF-κB 信号转导途径的激活,进而控制炎症的级联反应来对机体细胞起保护作用。更多还原

【Abstract】 The hemorrhagic shock and endotoxic shock are the commonreasons that lead the patients to death in clinical practice. Thereare many factors involved the pathological changes during the shock.A large quantity of data indicate that many signal transductionpathways are involved when the body treated with hemorrhage andendotoxin. A lot of anti-shock medicines have been used in theclinical treatment. Chinese traditional herbal medicines have manyadvantages such as low toxic, less side effects, general regulationand the source is abundant. Thereby seeking an effective naturalChinese traditional medicine is very important and practical forthe shock treatment. In this study we use “Shenmai”Injectionsolution to treat the endotoxic shock rats and “two-hit ”shockrats which treated by hemorrhage and lipopolysaccharide.In order to explore the molecular mechanism of the anti-shockeffect of Shenmai and observe the influence on TLR4 and IκB mRNAexpression in endotoxic shock and “two-hit”rats spleen. Theendotoxic shock rats were divided into Control, LPS, LPS+SM andLPS+Dex group respectively. The“two-hit”rats were divided intoHS, HS+LPS, HS+LPS+DEX and HS+LPS+SM group respectively. HS+LPSinjury model of rats were induced by hemorrhagic shock(MAP 40mmHgfor 10 minutes)followed by iv administration of lipopolysaccharide(LPS,1.5mg/kg).Four hours later, the lung TNF-αcontents weremeasured by ELISA, TLR4 mRNA and IκBαmRNA expression were assayedby RT-PCR, ultrastructural changes of the type Ⅱalveolar cellwere observed by transmission electron microscope. The most results are as follows: 1. In the endotoxic shock experimental groups, compared withthe Control group, TLR4 mRNA expression in the experimental groupswere increased significantly(P<0.05), of which LPS+SM group waslower obviously than LPS group(P<0.05); IκBαmRNA expression inthe experimental groups were decreased significantly(P<0.05), ofwhich LPS+SM group was higher obviously than LPS group(P<0.05). 2. In the “two-hit ”experimental groups, compared with theHS or HS+LPS group, TLR4 mRNA expression in the experimental groupswere increased significantly(P<0.05), of which HS+LPS+SM groupwas lower obviously than HS and HS+LPS group(P<0.05); IκBαmRNAexpression in the experimental groups were decreased significantly(P<0.05), of which HS+LPS+SM group was higher obviously than HSand HS+LPS group(P<0.05). 3. The lung TNF-αcontent level in HS+SM group and HS+LPS+SMgroup was obviously lower than that in HS group and HS+LPS group(P<0.05). 4.“Shenmai”has a protective role on the hung tissueinflammation and injury. On the observation of lung tissue underthe transmission electron microscope, in the group treated with“Shenmai”, the lung pathological injuries were alleviatedgreatly as compared to HS group and HS+LPS group. From the observation of the lung tissue and the expression of更多还原