CGRP通过抑制TNF-α介导单磷酰脂A对大鼠小肠的预适应延迟保护作用  

Calcitonin gene-related peptide mediates delayed preconditioning of monophosphoryl lipid A by decreasing tumor necrosis factor α in rat small intestine

作　　者：杨彩红[1] 张轩萍[1] 梁月琴 李焰 郝一彬[1] 

机构地区：[1]山西医科大学’药理教研室 [2]机能实验室,山西太原030001

出　　处：《中国病理生理杂志》2012年第4期669-674,共6页Chinese Journal of Pathophysiology

基　　金：山西医科大学博士启动基金资助项目(No.03201102)

摘　　要：目的:探讨降钙素基因相关肽(CGRP)介导的单磷酰脂A(MLA)对大鼠小肠的预适应延迟保护作用是否通过抑制肿瘤坏死因子α(TNF-α)而产生。方法:通过给予MLA(500μg.kg-1,ip)药物预适应,利用在体缺血再灌注(I/R)和原位灌流模型,检测外周血、灌流液和组织中乳酸脱氢酶(LDH)活性、丙二醛(MDA)含量和组织形态学改变以显示缺血再灌注损伤和药物的作用;通过放射免疫法测定血浆中CGRP和TNF-α含量探讨MLA预适应对大鼠小肠保护作用的机制。结果:与I/R组相比,给予MLA后可使I/R组LDH活性和MDA含量明显降低(P<0.05);同时MLA使I/R损伤大鼠CGRP含量显著升高,TNF-α含量下降(P<0.01)。使用CGRP拮抗剂CGRP8-37及辣椒素(capsaicin)耗竭CGRP后,均可消除MLA的这一作用。结论:MLA对在体、原位灌流大鼠小肠均诱导产生预适应的延迟保护作用;CGRP可能通过抑制TNF-α的产生而介导MLA诱导的预适应延迟保护作用。AIM： To explore whether monophosphoryl lipid A participates in the protective process of the delayed ischemic preconditioning in the small intestine of rats,and whether endogenous calcitonin gene-related peptide and tumor necrosis factor α are mediators in this process.METHODS： Intestinal ischemia was induced by occlusion of super mesenteric artery for 30 min,followed by reperfusion for 60 min.The ischemia/reperfusion（I/R） injury was made by 1 h ischemia and 15 min reperfusion in situ perfusion in rat small intestine.The intestine lesions were evaluated by the measurement of serum lactate dehydrogenase and malondialdehyde in the small intestinal tissues.In addition,calcitonin gene-related peptide and tumor necrosis factor α in plasma and superior mesenteric vein effluent were also examined.RESULTS： Pretreatment with monophosphoryl lipid A（500 μg/kg,ip） 24 h prior to I/R significantly alleviated the histolo-gical lesions of intestinal tissues,decreased serum level of lactate dehydrogenase and reduced the tissue content of malondialdehyde.Moreover,monophosphoryl lipid A markedly increased plasma concentrations of calcitonin gene-related peptide and decreased plasma concentrations of tumor necrosis factor α.Pretreatment with capasicin,which specifically depletes the neurotransmitter content of sensory nerves,or calcitonin gene-related peptide（8-37）,a selective calcitonin gene-related peptide receptor antagonist,inhibited the increase in calcitonin gene-related peptide release and subsequently abrogated the protective effect of monophosphoryl lipid A.CONCLUSION： Monophosphoryl lipid A pharmacologically mimics delayed preconditioning,which may be related to the stimulation of calcitonin gene-related peptide release and inhibition of tumor necrosis factor α production in rat small intestine.

关 键 词：单磷酰脂A 降钙素基因相关肽 肿瘤坏死因子 

分 类 号：R363[医药卫生—病理学]