血管活性肠肽对肺损伤大鼠Toll样受体mRNA表达的影响  

Effects of vasoactive intestinal peptide on Toll-like receptor （TLR） 2 mRNA and TLR4 mRNA expression on acute lung injury induced by lipopolysach aride in rat

作　　者：左文琼[1] 张育才[1] 龚小慧[1] 张宇鸣[1] 

机构地区：[1]上海交通大学附属儿童医院急救中心上海交通大学儿科危重病研究所,200040

出　　处：《中华儿科杂志》2010年第1期19-23,共5页Chinese Journal of Pediatrics

基　　金：上海市卫生局科技发展基金（05041）;中华儿科杂志第二届百利基金

摘　　要：目的探讨血管活性肠肽（vasoachve intestinal peptide，VIP）对内毒素（脂多糖，lipopolysaccharide，LPS）致休克大鼠肺损伤后Toll样受体（Toll—like receptor，TLR）2和TLR4mRNA表达的影响。方法40只SD大鼠，随机分为LPS组（16只）、LPS＋VIP组（16只）和对照组（8只）。LPS组尾静脉注射LPS（E．coli05585）10mg／kg；LPS＋VIP组尾静脉注射LPS10mg／kg后注射VIP5nmol／kg；对照组尾静脉注射等容量生理盐水。分别于注射后6h和24h处死，留取肺标本，RT—PCR检测肺TLR2／4mRNA表达，并观察24h时肺组织病理变化。结果（1）肺组织病理改变：制模24h时，光镜和透射电镜下，LPS组见肺泡间隔弥漫性增宽、炎性细胞浸润，隔内毛细血管不同程度充血，肺泡壁增厚，肺泡腔结构破坏、炎性细胞浸润、出血、间质水肿、细胞器破坏，LPS＋VIP组病变较轻。（2）TLR2／4mRNA表达：注射LPS后6h、24h，肺组织TLR2／4mRNA表达升高（F=16．638，P=0．000；t=5．876，P=0．000）；24h时LPS＋VIP组TLR2／4mRNA表达低于LPS组（F=16．676，P=0．000；t=3．946，P〈0．001）。结论LPS致休克大鼠肺损伤时，肺组织TLR2／4mRNA表达增强。VIP可减轻LPS所致肺损伤，其机制可能与下调重要炎症基因TLR2／4mRNA表达有关。Objective Vasoactive intestinal peptide （VIP） is a neuro-peptide that can modulate immunity. Previous studies indicated that VIP can attenuate the deleterious consequences of severe sepsis and septic shock by regulating production of inflammatory cytokines in immune activated cells. The signaling induced by bacterial components occurs primarily through Toll like receptors （TLRs）. TLRs have been recognized to play a key role in pathogen recognition and innate immunity. It was convincingly demonstrated that lung is one of early suffered disaster organ and may trigger multiple organ dysfunction syndrome in sepsis. The present study was conducted to investigate the effects of VIP on TLR2/4 mRNA expressions on acute lung injury of endotoxie shock induced by lipopolysaecharide （LPS） in rat. Method Forty Sprague- Dawley rats were randomly divided into 3 groups, i. e. , LPS shock group （ n = 16） , LPS ＋ VIP group （ n = 16 ） ,and control group （n =8）. LPS shock model was established by LPS （E. coli 055B5 10 mg/kg） with tail intravenous injection. The rats in LPS ＋ VIP group were given a bolus of 5 nmol VIP intravenous injection follow by LPS. The rats in control group were given normal saline. The rats were sacrificed at 6 h, 24 h after being injected. The lung tissues were collected. The TLR2 mRNA and TLR4 mRNA expressions were detected by RT-PCR from the lung tissues. Pathological changes of the lungs were observed by light microscope and electron microscope 24 h after LPS injection. Result （ 1 ） Lung histopathology： the alveolar space was full with leukocyte, necrotic cells, segmental hemorrhage and protein effusion. Partial alveolar space was enlarged, lung interstitial edema were observed in LPS shock group. However, pathological changes of LPS ＋ VIP group were milder than those in LPS shock group. （ 2 ） The expressions of TLR2 mRNA and TLR4 mRNA were significantly higher in LPS shock group compared with those of the control group（ F =16. 638 ,P = 0. 000 ;t = 5. 876, P =

关 键 词：TOLL样受体 血管活性肠肽 脂多糖类 全身炎症反应综合征 大鼠 

分 类 号：R285.5[医药卫生—中药学]