中华儿科杂志
中華兒科雜誌
중화인과잡지
Chinese Journal of Pediatrics
2010年
1期
19-23
,共5页
左文琼%张育才%龚小慧%张宇鸣
左文瓊%張育纔%龔小慧%張宇鳴
좌문경%장육재%공소혜%장우명
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
TOLL樣受體%血管活性腸肽%脂多糖類%全身炎癥反應綜閤徵%大鼠
TOLL양수체%혈관활성장태%지다당류%전신염증반응종합정%대서
Toll-like receptons%Vasoactive intestinal peptide: Endotoxins%Systemic inflammatory response syndrome%Rats
目的 探讨血管活性肠肽(vasoactive intestinal peptide,VIP)对内毒素(脂多糖,lipopolysaceberide,LPS)致休克大鼠肺损伤后Toll样受体(Toll-like receptor,TLR)2和TLR4 mRNA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.coli O_(55)B_5)10 mg/kg;LPS+VIP组尾静脉注射LPS 10 ms/kg后注射VIP 5 nmol/kg;对照组尾静脉注射等容量生理盐水.分别于注射后6 h和24 h处死,留取肺标本,RT-PCR检测肺TLR2/4 mRNA表达,并观察24 h时肺组织病理变化.结果 (1)肺组织病理改变:制模24 h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)TLR2/4 mRNA表达:注射LPS后6 h、24 h,肺组织TLR2/4 mRNA表达升高(F=16.638,P=0.000;t=5.876,P=0.000);24 h时LPs+VIP组TLR2/4 mRNA表达低于LPS组(F=16.676,P=0.000;t=3.9,16,P<0.001).结论 LPS致休克大鼠肺损伤时,肺组织TLR2/4 mRNA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TLR2/4 mRNA表达有关.
目的 探討血管活性腸肽(vasoactive intestinal peptide,VIP)對內毒素(脂多糖,lipopolysaceberide,LPS)緻休剋大鼠肺損傷後Toll樣受體(Toll-like receptor,TLR)2和TLR4 mRNA錶達的影響.方法 40隻SD大鼠,隨機分為LPS組(16隻)、LPS+VIP組(16隻)和對照組(8隻).LPS組尾靜脈註射LPS(E.coli O_(55)B_5)10 mg/kg;LPS+VIP組尾靜脈註射LPS 10 ms/kg後註射VIP 5 nmol/kg;對照組尾靜脈註射等容量生理鹽水.分彆于註射後6 h和24 h處死,留取肺標本,RT-PCR檢測肺TLR2/4 mRNA錶達,併觀察24 h時肺組織病理變化.結果 (1)肺組織病理改變:製模24 h時.光鏡和透射電鏡下,LPS組見肺泡間隔瀰漫性增寬、炎性細胞浸潤,隔內毛細血管不同程度充血,肺泡壁增厚,肺泡腔結構破壞、炎性細胞浸潤、齣血、間質水腫、細胞器破壞,LPS+VIP組病變較輕.(2)TLR2/4 mRNA錶達:註射LPS後6 h、24 h,肺組織TLR2/4 mRNA錶達升高(F=16.638,P=0.000;t=5.876,P=0.000);24 h時LPs+VIP組TLR2/4 mRNA錶達低于LPS組(F=16.676,P=0.000;t=3.9,16,P<0.001).結論 LPS緻休剋大鼠肺損傷時,肺組織TLR2/4 mRNA錶達增彊.VIP可減輕LPS所緻肺損傷,其機製可能與下調重要炎癥基因TLR2/4 mRNA錶達有關.
목적 탐토혈관활성장태(vasoactive intestinal peptide,VIP)대내독소(지다당,lipopolysaceberide,LPS)치휴극대서폐손상후Toll양수체(Toll-like receptor,TLR)2화TLR4 mRNA표체적영향.방법 40지SD대서,수궤분위LPS조(16지)、LPS+VIP조(16지)화대조조(8지).LPS조미정맥주사LPS(E.coli O_(55)B_5)10 mg/kg;LPS+VIP조미정맥주사LPS 10 ms/kg후주사VIP 5 nmol/kg;대조조미정맥주사등용량생리염수.분별우주사후6 h화24 h처사,류취폐표본,RT-PCR검측폐TLR2/4 mRNA표체,병관찰24 h시폐조직병리변화.결과 (1)폐조직병리개변:제모24 h시.광경화투사전경하,LPS조견폐포간격미만성증관、염성세포침윤,격내모세혈관불동정도충혈,폐포벽증후,폐포강결구파배、염성세포침윤、출혈、간질수종、세포기파배,LPS+VIP조병변교경.(2)TLR2/4 mRNA표체:주사LPS후6 h、24 h,폐조직TLR2/4 mRNA표체승고(F=16.638,P=0.000;t=5.876,P=0.000);24 h시LPs+VIP조TLR2/4 mRNA표체저우LPS조(F=16.676,P=0.000;t=3.9,16,P<0.001).결론 LPS치휴극대서폐손상시,폐조직TLR2/4 mRNA표체증강.VIP가감경LPS소치폐손상,기궤제가능여하조중요염증기인TLR2/4 mRNA표체유관.
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 TLR2/4,4 mRNA expressions on acute lung injury of endotoxic shock induced by lipolysaccharide(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 O_(55)B_5 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 iniected.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 wag full with leukocyte,necrotic cells,segmental hemorrhage and protein effusion.Partial alveo]ar space wag enlarged,lung interstitial edema were observed in LPS 8hock 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 ofthe control group(F= 16.638,P=0.000;t=5.876,P=0.000),TLR2 mRNA and TLR4 mRNA expression on 24 h was down-regulated in LPS+VIP shock subgroup than those in LPS shock subgroup(F=16.676,P=0.000;t=3.946,P<0.001).Conclusion Expressions of TLR2 mRNA and TLR4 mRNA were up-regulated on LPS induced lung injury in rats.VIP mitigated lung injury induced by LPS,which may be related to TLR2 mRNA and TLR4 mRNA down-regulation of expression.The effect of VIP may suggest a protective mechanism in sepsis.VIP may play a potential protective role in severe jnfection.
