旋转刺激对脓毒症大鼠外周炎症反应的影响
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摘要
目的观察旋转刺激(模拟运动病)对脓毒症大鼠外周炎症反应的影响,以明确运动病大鼠内毒素敏感性变化的机制。方法采用仿制Crampton旋转刺激器建立大鼠运动病模型。将32只大鼠随机分为4组:正常对照组(CO组)、旋转刺激组(RO组)、内毒素损伤组(LP组)、旋转刺激+内毒素损伤组(RL组)。其中RO组仅给予旋转刺激90 min,LP组给予非致死量内毒素脂多糖(lipopolysaccharide,LPS)3 mg/kg腹腔内注射,RL组给予LPS腹腔注射后再接受旋转刺激。分别测定各组的血清炎症介质以及皮质醇(cortisol,CORT)水平。结果 (1)血清炎症介质水平比较,与CO组比较,RO组对促炎因子肿瘤坏死因子α(tumor necrosis factor alpha,TNF-α)、白细胞介素1β(interleukin 1 beta,IL-1β)、白细胞介素6(interleukin 6,IL-6)水平无明显影响,组间比较均无统计学差异(P>0.05),但可以引起抗炎因子白细胞介素10(interleukin 10,IL-10)的升高(P<0.05);LP组和RL组促炎和抗炎因子水平均明显高于CO组(P<0.01),但RL组促炎因子TNF-α、IL-1β和抗炎因子IL-10水平均低于LP组,组间比较均有统计学差异(P<0.01)。(2)血清神经递质和CORT水平比较,与CO组比较,RO组外周血的乙酰胆碱(acetylcholine,Ach)和去甲肾上腺素(noradrenaline,NA)水平明显升高(P<0.01),CORT水平无明显变化(P>0.05),LP组的Ach水平无明显变化(P>0.05),但NA和CORT水平显著升高(P<0.01或0.05);与LP组比较,RL组的Ach和NA水平明显升高(P<0.01),但CORT水平无明显差异(P>0.05)。结论旋转刺激可抑制脓毒症大鼠外周的抗炎和促炎反应,其作用可能与过度应激导致机体免疫功能低下有关。
Objective To observe the effects of rotation stimulation(simulated motion sickness)on peripheral inflammatory response in septic rats,and clarify the mechanism of sensitivity changes of endotoxin in rats with motion sickness.Methods The rat model of motion sickness was established by using the imitated Crampton rotation simulator.Thirty-two rats were randomly divided into four groups:normal control group(CO group),rotation stimulation group(RO group),lipopolysaccharide(LPS)injury group(LP group),ratation stimulation plus LPS injury group(RL group).In RO group,rats were received rotation stimulation for 90 minutes,rats in LP group were given a nonlethal dose of intraperitoneal LPS injection(3 mg/kg),while in RL group,rats were received ratation stimulation after LPS injection.Serum levels of inflammatory mediators and cortisol(CORT)were measured in each group.Results(1)Serum inflammatory cytokines levels.As compared with CO group,simple ratation stimulation had no significant effects on the levels of tumor necrosis factor alpha(TNF-α),interleukin 1 beta(IL-1β)and interleukin 6(IL-6)in RO group(P>0.05),but it could increase interleukin 10(IL-10)level(P<0.05).The levels of TNF-α,IL-1β,IL-6 and IL-10 in LP and RL groups were significantly higher than those in CO group(P<0.01).Rotation stimulation could significantly inhibit the levels of proinflammatory cytokines(TNF-αand IL-1β)and anti-inflammatory cytokines(IL-10)in RL group as compared with those in LP group(P<0.01).(2)Serum acetylcholine(Ach)and CORT levels.As compared with CO group,serum levels of Ach and noradrenaline(NA)were significantly increased by simple ratation stimulation in RO group(P<0.01),but had no effect on CORT levels(P>0.05).LPS injection could induce the elevation of NA and CORT levels(P<0.01 or 0.05),but had no effect on Ach levels(P>0.05)in LP group.The RL group had higher levels of Ach and NA than those in LP group(P <0.01),but had no significant difference of CORT levels between two groups(P >0.05).Conclusion Rotation stimulation can inhibit the peripheral anti-inflammatory and proinflammatory responses in septic rats,which may relate to immune dysfunction causing by excessive stress.
Objective To observe the effects of rotation stimulation(simulated motion sickness)on peripheral inflammatory response in septic rats,and clarify the mechanism of sensitivity changes of endotoxin in rats with motion sickness.Methods The rat model of motion sickness was established by using the imitated Crampton rotation simulator.Thirty-two rats were randomly divided into four groups:normal control group(CO group),rotation stimulation group(RO group),lipopolysaccharide(LPS)injury group(LP group),ratation stimulation plus LPS injury group(RL group).In RO group,rats were received rotation stimulation for 90 minutes,rats in LP group were given a nonlethal dose of intraperitoneal LPS injection(3 mg/kg),while in RL group,rats were received ratation stimulation after LPS injection.Serum levels of inflammatory mediators and cortisol(CORT)were measured in each group.Results(1)Serum inflammatory cytokines levels.As compared with CO group,simple ratation stimulation had no significant effects on the levels of tumor necrosis factor alpha(TNF-α),interleukin 1 beta(IL-1β)and interleukin 6(IL-6)in RO group(P>0.05),but it could increase interleukin 10(IL-10)level(P<0.05).The levels of TNF-α,IL-1β,IL-6 and IL-10 in LP and RL groups were significantly higher than those in CO group(P<0.01).Rotation stimulation could significantly inhibit the levels of proinflammatory cytokines(TNF-αand IL-1β)and anti-inflammatory cytokines(IL-10)in RL group as compared with those in LP group(P<0.01).(2)Serum acetylcholine(Ach)and CORT levels.As compared with CO group,serum levels of Ach and noradrenaline(NA)were significantly increased by simple ratation stimulation in RO group(P<0.01),but had no effect on CORT levels(P>0.05).LPS injection could induce the elevation of NA and CORT levels(P<0.01 or 0.05),but had no effect on Ach levels(P>0.05)in LP group.The RL group had higher levels of Ach and NA than those in LP group(P <0.01),but had no significant difference of CORT levels between two groups(P >0.05).Conclusion Rotation stimulation can inhibit the peripheral anti-inflammatory and proinflammatory responses in septic rats,which may relate to immune dysfunction causing by excessive stress.
引文
[1]马文领,郑璇,郭俊生.运动病神经生物学机制研究进展[J].中国公共卫生,2007,23(3):307-309
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[7]马国亮,吴新文,迮浩城,等.运动病大鼠对异氟烷麻醉的敏感性及神经递质的变化[J].中华航海医学与高气压医学杂志,2013,20(3):155-158
[8]吴新文,李建玉,曹云飞,等.模拟航海运动病大鼠对异氟烷和七氟烷敏感性的变化[J].广东医学,2011,32(22):2932-2934
[9]蔡懿灵,马文领,李敏,等.旋转刺激条件下大鼠行为变化的研究[J].航天医学与医学工程,2005,18(2):98-101
[10]姜新,谢培增,周赤龙,等.不同救治环境下海战伤救治的效果观察[J].中华航海医学与高气压医学杂志,2008,15(6):339-342
[11]邱晓霞,姜正林,周维镕,等.大鼠运动病敏感性与血浆CORT、促肾上腺皮质激素水平关系[J].中华航海医学与高气压医学杂志(医学版),2005,12(1):45-46,49
[12]汤冠荣,蒋锐,姜正林,等.前庭功能锻炼对运动病大鼠血浆应激相关激素水平的影响[J].中国病理生理杂志,2013,29(6):1065-1069
[13]田大为,郑颖鹃,谢海燕,等.运动病的研究进展[J].军事医学,2014,38(3):230-233
[14]Sheehan SE,Oman CM,Duda KR.Motion sickness:a cholinomimetic agent hypothesis[J].J Vestib Res,2011,21(4):209-217
[15]Tracey KJ.Physiology and immunology of the cholinergic antiinflammatory pathway[J].J Clin Invest,2007,117(2):289-296
[16]Bellavance MA,Rivest S.The HPA-immune axis and the immunomodulatory actions of glucocorticoids in the brain[J].Front Immunol,2014,5:1-13
[17]Eisenman LM.Motion sickness may be caused by a neurohumoral action of acetylcholine[J].Med Hypotheses,2009,73(5):790-793
[18]Rosas-Ballina M,Tracey KJ.Cholinergic control of inflammation[J].J Intern Med,2009,265(6):663-679
[19]Wang DW,Yin YM,Yao YM.Vagal modulation of the inflammatory response in sepsis[J].Int Rev Immunol,2016,35(5):415-433
[20]Báez-Pagán CA,Delgado-Vélez M,Lasalde-Dominicci JA.Activation of the macrophageα7 nicotinic acetylcholine receptor and control of inflammation[J].J Neuroimmune Pharmacol,2015,10(3):468-476
[2]孔哲,牛丽静,高萱,等.运动病的神经通路研究进展[J].河北师范大学学报(自然科学版),2005,29(1):88-90
[3]Oman CM,Cullen KE.Brainstem processing of vestibular sensory exafference:implications for motion sickness etiology[J].Exp Brain Res,2014,232(8):2483-2492
[4]Kumar V,Sharma A.Is neuroimmunomodulation a future therapeutic approach for sepsis?[J].Int Immunopharmacol,2010,10(1):9-17
[5]Johnston GR,Webster NR.Cytokines and the immunomodulatory function of the vagus nerve[J].Br J Anaesth,2009,102(4):453-462
[6]房巍,梁小燕,姚橹,等.旋转刺激对大鼠的内毒素敏感性及脑干神经递质含量的影响[J].华南国防医学杂志,2016,30(12):766-768
[7]马国亮,吴新文,迮浩城,等.运动病大鼠对异氟烷麻醉的敏感性及神经递质的变化[J].中华航海医学与高气压医学杂志,2013,20(3):155-158
[8]吴新文,李建玉,曹云飞,等.模拟航海运动病大鼠对异氟烷和七氟烷敏感性的变化[J].广东医学,2011,32(22):2932-2934
[9]蔡懿灵,马文领,李敏,等.旋转刺激条件下大鼠行为变化的研究[J].航天医学与医学工程,2005,18(2):98-101
[10]姜新,谢培增,周赤龙,等.不同救治环境下海战伤救治的效果观察[J].中华航海医学与高气压医学杂志,2008,15(6):339-342
[11]邱晓霞,姜正林,周维镕,等.大鼠运动病敏感性与血浆CORT、促肾上腺皮质激素水平关系[J].中华航海医学与高气压医学杂志(医学版),2005,12(1):45-46,49
[12]汤冠荣,蒋锐,姜正林,等.前庭功能锻炼对运动病大鼠血浆应激相关激素水平的影响[J].中国病理生理杂志,2013,29(6):1065-1069
[13]田大为,郑颖鹃,谢海燕,等.运动病的研究进展[J].军事医学,2014,38(3):230-233
[14]Sheehan SE,Oman CM,Duda KR.Motion sickness:a cholinomimetic agent hypothesis[J].J Vestib Res,2011,21(4):209-217
[15]Tracey KJ.Physiology and immunology of the cholinergic antiinflammatory pathway[J].J Clin Invest,2007,117(2):289-296
[16]Bellavance MA,Rivest S.The HPA-immune axis and the immunomodulatory actions of glucocorticoids in the brain[J].Front Immunol,2014,5:1-13
[17]Eisenman LM.Motion sickness may be caused by a neurohumoral action of acetylcholine[J].Med Hypotheses,2009,73(5):790-793
[18]Rosas-Ballina M,Tracey KJ.Cholinergic control of inflammation[J].J Intern Med,2009,265(6):663-679
[19]Wang DW,Yin YM,Yao YM.Vagal modulation of the inflammatory response in sepsis[J].Int Rev Immunol,2016,35(5):415-433
[20]Báez-Pagán CA,Delgado-Vélez M,Lasalde-Dominicci JA.Activation of the macrophageα7 nicotinic acetylcholine receptor and control of inflammation[J].J Neuroimmune Pharmacol,2015,10(3):468-476