【作者】 樊哲；

【导师】 田晓峰；

【作者基本信息】 大连医科大学 ， 外科学， 2009， 硕士

【摘要】 肠缺血再灌注损伤是严重创伤、休克等疾病治疗过程中经常发生的病理生理过程,可导致许多严重并发症,是多脏器功能衰竭(MODS)发生、发展的重要原因之一。肠缺血再灌注不仅损伤肠道本身,对远隔器官如肝、肺的功能均产生严重影响。核转录因子κB(NFκB)能调节许多炎症介质的基因转录和表达。NFκB的活化在急性肺损伤的发生发展中起重要的作用。姜黄是类姜黄素家族成员中的一员,姜黄属植物的根茎和块根中提取的黄色酚类物质,研究表明姜黄具有强大的抗氧化和抗炎作用,可以作为NFκB的阻滞剂发挥很多作用。目的:探讨中药姜黄提取物(curcumin)对大鼠肠缺血再灌注肺损伤肺的保护作用及其机制。方法:雄性Wistar大鼠24只随机分成对照组(control组,n=6)、模型组(IIR组,n=6)、1 mg/kg姜黄处理组(低剂量姜黄组,n=6)和5 mg/kg姜黄处理组(高剂量姜黄组,n=6)。IIR组、低剂量姜黄组和高剂量姜黄组大鼠行肠系膜上动脉夹闭1小时再灌注2小时。处理组于再灌注前10分钟分别以1 mg/kg和5 mg/kg姜黄行左股静脉注射,对照组及IIR组给予等量生理盐水。观察大鼠肠、肺组织病理学、肺泡灌洗液蛋白含量,检测血清IL-6和TNF-α水平,测定肺组织匀浆SOD、MPO水平,采用免疫组化法观察肺组织ICAM-1、NFκB表达并用Western-blot法检测其含量。结果:肠缺血1小时再灌注2小时可导致严重的肺组织的损伤,表现为肺组织有明显的水肿、渗出和炎性细胞浸润。与对照组相比,肺泡灌洗液蛋白含量(BALF)升高(P<0.01),肺组织SOD活性降低(P<0.01),肺组织MPO活性增强(P<0.01);血清TNF-α、IL-6水平亦有显著升高(P<0.01、P<0.01);肺组织ICAM-1、NFκB表达增强。与IIR组相比,1 mg/kg姜黄处理和5 mg/kg姜黄处理组肺组织的病理表现及损伤程度明显减轻,BALF降低(P<0.01),SOD活性升高(P<0.05),血清TNF-α、IL-6水平降低(P<0.01、P<0.01),肺组织ICAM-1、NFκB表达减弱。但MPO活性仅在1 mg/kg姜黄处理组有显著降低(P<0.01)。结论:(1)肠缺血1小时再灌注2小时引起严重的肺损伤;(2)肠缺血再灌注引起肺损伤的机制复杂,NFκB激活参与了这一损伤过程;(3)姜黄可以保护肠缺血再灌注引发的肺损伤。更多还原

【Abstract】 Intestine ischemia reperfusion (IIR) is a pathophysiologic process frequently during the therapy of many diseases such as serious trauma and shock and may result in many serious complications. The enterogenic infection is the effect induced by the impaired intestinal mucosal barrier, and it is the key cause that leads to systemic inflammatory response syndrome and multiple organ dysfunction syndrome. Intestine ischemia reperfusion not only hurts the intestines but also causes the remote organs such as lung failure. The transcription factor nuclear factor kappaB (NFκB) can regulate transcription and expression of many inflammatory mediators. The research has proved that the lung damage caused by IIR is related with NFκB, and the activation of NFκB plays an important role in the IIR. Curcumin, a member of the curcuminoid family of compounds, is a yellow colored phenolic pigment obtained from powdered rhizome. Present research discovered that curcumin has powerful anti-inflammatory and antibacterial effects. As an inhibitor of NFκB, it has many effective effects.Objective: To investigate the protection of curcumin on lung during intestinal ischemia reperfusion injury (IIR) and to examine the possible mechanism of this process.Method: Rats were randomly divided into 4 groups: control group, IIR group, the 1 mg/kg curcumin treated (low dosage group) and the 5 mg/kg curcumin treated (high dosage group) (n=6). The IIR model was established by clamping superior mesenteric artery (SMA) for 1 hour and reperfusion for 2 hours. The 2 treated groups were administrated with femoral vein injection of 1 mg/kg and 5 mg/kg curcumin 10 min before reperfusion. Lung histology and bronchia alveolus lung fluid (BALF) protein were assayed. Serum IL-6 and TNF-α, lung superoxide dismutase (SOD) and myeloper- oxidase (MPO) as well as the expression level of NFκB and ICAM-1 were measured.Result: Lung injury induced by intestinal IIR, was characterized by edema, hemorrhage and neutrophil infiltration as well as the significant rising of BALF protein. In model groups, compared with control group, the levels of serum IL-6, TNF-α, lung MPO increased (P<0.01, P<0.01, P<0.01) and lung SOD decreased (P<0.01) in I/R group. Strong positive expression of NFκB P65 and ICAM-1 was observed. After the administration of low and high dosage curcumin, the level of BALF protein, serum IL-6, TNF-α, decreased significantly (P<0.01, P<0.01, P<0.01) and lung SOD increased obviously (P<0.05) while lung MPO decreased (P<0.01) only in the low dosage group, the expression of NFκB P65 and ICAM-1 decreased when compared to IIR group.Conclusion: (1) This study demonstrated that intestinal IIR may result in severe lung damage; (2) The mechanism of lung injury induced by IIR is complicated, which has relation with the activation of NFκB; (3) Curcumin can protect lung against IIR injury which may be related with inhibiting the activation of NFκB.更多还原