胆碱能抗炎通路对内毒素复合油酸致大鼠急性肺损伤的影响  

Effect of the Cholinergic Anti-inflammatory Pathway on Acute Lung Injury Induced by Oleic Acid and Lipopolysaccharide in Rats

作　　者：郑晖[1] 许绍发[2] 贾红彦[3] 古淑香[3] 

机构地区：[1]首都医科大学附属北京胸科医院麻醉科,北京101149 [2]首都医科大学附属北京胸科医院胸外科,北京101149 [3]首都医科大学附属北京胸科医院结核病分子生物学实验室,北京101149

出　　处：《结核病与胸部肿瘤》2012年第3期188-193,共6页Tuberculosis and Thoracic Tumor

摘　　要：目的研究胆碱能抗炎通路（cholinergic anti-inflammatory pathway，CAP）对内毒素复合油酸2次打击致大鼠急性肺损伤（acute lung injury，ALI）的影响及其可能的作用机制。方法24只雄性Wistar大鼠，体质量250±20g。按数字表法将大鼠随机分为4组，每组6只。①对照组（control group，C组）：腹腔注射生理盐水10mL·kg^-1；②急性肺损伤（ALI）组：腹腔注射1％内毒素（lipopolysaccharide，LPS）10mg·kg^-1，30min后静脉注射油酸（oleic acid，OA）0．15mL·kg^-1；③电刺激（stimulation，ST）组：右颈迷走神经干连接刺激电极，以5V、2ms、1Hz强度持续刺激神经10min，腹腔注射1％LPS10mg·kg^-1，再持续刺激神经10min，20min后静脉注射OA0．15mL·kg^-1；④他克林（tetrahydroaminoacridine，THA）组：静脉注射胆碱酯酶抑制剂THA1．5mg·kg^-1，10min后行急性肺损伤操作。各组动物均于130min后从颈总动脉采血1mL行血气分析，处死动物采集标本，分别检测肺组织Toll．样受体-2（Toll-like receptor-2，TLR2）和TLR4mRNA、核转录因子κB（nuclear factor kappa-B，NF-κB）p^65、血清白介素-6（interleukin-6，IL-6）、肺组织髓过氧化物酶（mycloperoxidase，MPO）含量和肺组织湿质量-干质量比（wet weight／dry weight，W／D），HE染色观察左肺组织病理学改变。结果ALI组与C组比较，pH和动脉氧分压（partial pressure of oxygen，PaO2）均显著下降，二氧化碳分压（partial pressure of carbon dioxide，PaCO2）显著升高；肺泡破坏严重，有大量组织液渗出；肺组织W／D及MPO活性均显著增高；肺组织NF-κB P^65蛋白表达明显增强；血清IL-6浓度显著升高：与C组相比，其余3个实验组肺组织TLR2和TLR4 mRNA表达均显著增加，组间比较差异无统计学意义；ST组和THA组与ALI组比较，pH和PaO2均显著升高，PaCO2显著下降；肺组织病理改变明显改善；肺组织W／D及MPO活性均显著降低：肺组Objective To investigate the effect of the cholinergic anti-inflammatory pathway （CAP） on the acute lung injury （ALl） induced by oleic acid and lipopolysaccharide in rats. Methods Twenty-four male Wistar rats were randomly divided into four groups （n=6） . （1） Control group：saline, 10 mL . kg^-1, intraperitoneally,（2） ALI group：oleic acid was administrated with 0.15 mL . kg^-1 intravenously 30 min after intraperitoneal injection of lipopolysaccharide （LPS） with 10 mg. kg^-1, （3） stimulation （ST） group： electrical stimulation （5V, 2 ms, 1Hz） of the right cervical vagus nerve for 10 min before and after LPS and OA administration, （4） tetrahydroaminoacridine （THA） group： tetrahydroaminoacridine was given at 1.5 mg. kg i intravenously before LPS and OA administration. Blood and tissue samples were collected 130 minutes after the first drug injection in all groups.TLR2 and TLP4 mRNA, NF- κ Bp65, MPO of lung tissue and IL-6 of serum were measured respectively.The blood gas analysis, wet weight to dry weight ratio （W/D） of right lung, and pathological changes were also observed. Results As compared with group C, the pH and PaO2 decreased markedly in group ALl while the histopathologic changes of lung tissue showed alveolar hemorrhage, necrosis and proteinaceous alveolar edema.W/ D ratio, the activity of MPO, NF-κB expression and the level of serum IL-6 significantly increased. As compared with group C, the expressions of the TLR2 and TLR4 mRNA were markedly increased in other three groups, but no significant change was found among these three groups. As compared with group ALI, pH and PaO2 markedly increased in group ST and group THA as well as PaCO2 decreased.The lung tissue showed slightpathological changes.W/D ratio and the activity of MPO were significantly reduced. The expression of NF- κ B p 65 protein and the amount of serum IL-6 markedly decreased. Conclusions Electrical stimulation of the vagus nerve or administration of THA intravenously could protect t

关 键 词：胆碱能抗炎通路 急性肺损伤 Toll-样受体 

分 类 号：R-332[医药卫生]