【作者】 彭春荣；

【导师】 马超英；

【作者基本信息】 西南交通大学 ， 中药学， 2011， 硕士

【摘要】 大承气汤是中医治疗阳明腑实证的主方,近年临床用于感染性疾病所致的内毒素血症,效果显著。但由于其药效作用机理和物质基础目前尚不清楚,因而其剂型改革和质量标准难以确认,致使该方临床应用和该类新药研制受到一定限制。目的：以血浆内毒素、免疫组化、生化检测和组织形态学观察为指标,评价大承气汤及其不同提取部位对小鼠内毒素血症的治疗作用,探讨大承气汤及其不同提取部位的药效机制,为探讨大承气汤抗内毒素血症的物质基础提供依据。方法：采用动物实验研究的方法,将126只雄性昆明小鼠随机分为空白组、模型组、大承气汤组、氯仿组、乙酸乙酯组、乙醇组和醇沉组,每组18只,空白组腹腔消毒注射生理盐水(10mg/kg),其余各组腹腔消毒注射LPS(10mg/kg),治疗组于攻毒前0.5h、攻毒后1h和取血前0.5h给予药液8.11g/kg·d灌胃；空白组和模型组于攻毒前0.5h、攻毒后1h和取血前0.5h按比例给予生理盐水,8h后在无菌条件下采集心室血0.5ml进行血浆内毒素检测,取部分肝脏进行免疫组化检测,取心、肝、脾、肾进行组织学观察,探讨大承气汤及其不同部位对于内毒素血症的治疗作用；同时将昆明小鼠54只,随机分为空白组、模型组及大黄酸组,每组18只,灌胃及造模方法同上,观察大黄酸对内毒素血症小鼠血浆内毒素的变化以及肝组织炎性细胞因子、肝组织病理切片变化,探讨大黄酸对内毒素血症动物的保护作用。结果：大承气汤组、乙酸乙酯组和大黄酸组对小鼠的血浆内毒素、TNF-α、IL-1β、IL-10、MDA、SOD和小鼠心、肝、脾、肾组织病理炎症活动度等指标的改善,明显优于其他组。结论：大承气汤、大承气汤的乙酸乙酯部位和大黄酸对小鼠内毒素血症有显著的治疗作用,其机制可能是：通过促进胃肠功能恢复,防止细菌移位,减少内毒素吸收；减轻过度的炎症反应,改善全身症状,稳定体内的免疫平衡；清除氧自由基,保护肝窦内皮细胞及心、肝、肾等多脏器功能等。更多还原

【Abstract】 the Da Cheng Qi Decoction (DCQTD) is the main prescription of curing for empirical Yang Ming organs in traditional Chinese medicine; it has been used for curing endotoxemia and has obvious effect in recent years. But up to now the mechanism of its action especially the relationship between clinical effects and chemical components of DCQD is still controversial, so its formulation reform and quality standards can’t be fixed, then its clinical application and new drugs’research are subjected to certain restrictions.Objective:This text evaluates the treatment of DCQD and its different extracts on endotoxemia by the index of plasma endotoxin, immunohistochemistry, biochemical testing and histological, then explore the mechanisms and efficacy of parts of DCQD, and then provide the basis for exploring the material basis of efficacy and mechanism of action of DCQD.Methods:Divide 126 male KM mice into 7 groups randomly, groups are separately control group,model group, DCQD group, chloroform group, ethyl group, ethanol group and ethanol precipitation Group,18 KM mice each group. Mice of control group are abdominal injected NS(10mg/kg) sterile, the others are abdominal injected LPS (10mg/kg) the treatment groups are given remedy liquid (8.11g/kg·d) by Ig at 0.5h before and lh after attacking and 0.5h before collecting blood; the control group and model group are given NS at the same time.8 hours later, collect 0.5ml ventricular blood under sterile conditions and detect the plasma ET, collect parts of the liver to have the immunohistochemistry, and take the heart. Liver and kidney to have the histological. Then explore the treatment of DCQD and its different parts in Endtoxemia; at the same time, divide 54 male KM mice into 3 groups randomly, groups are control group, model group and rhein group,18 KM mice each group, the ways of Ig and modeling are the same as the above. And then observe the changes of endotoxin, inflammatory cytokines in liver tissue and liver tissue biopsy in mice of endtoxemia by modeling, to explore the protecting effect of rhein on mice of endtoxemia.Results:The effect of DCQD group and ethyl group are significantly better than other curing groups on improving the plasma endotoxin, TNF-α, IL-1β, IL-10, MDA and the pathological inflammatory activity of heart, liver and kidney.Conclusions:The DCQD and its ethyl acetate and rhein all have obvious effects on Endotoxemia, the mechanism may be the following:promote the recovery of gastrointestinal function, prevent the bacterial translocation, decrease the absorption of endotoxin; reduce the excessive inflammatory response, improve symptoms, stabilize the balance of the body’s immune; scavenging oxygen free radicals, protect liver sinusoidal endothelial cells; and protect the heart, liver, kidney and other organ functions and so on.更多还原