早期应激对SD大鼠内脏感觉和肠道炎症的影响
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摘要
目的:1、探讨应激事件(包括早期应激与急性应激)对大鼠肠道炎症细胞浸润的影响;2、探讨早期应激与急性应激对大鼠内脏感觉的影响。
方法:36只雄性新生SD幼鼠,分为正常对照组(CON,n=12)、母婴分离组(MS,n=12)、急性避水应激组(WA,n=12)。MS组幼鼠出生第2天开始进行母婴分离,持续至出生后第3周。WA组动物于出生后第60天接受避水实验。2月龄时各组大鼠接受直肠气囊扩张大鼠腹部回缩反射(AWR)评分和腹壁肌电测定;结束后取结肠组织作常规病理学检查和肥大细胞计数(甲苯胺蓝染色法)、并测定结肠黏膜孵育上清液白细胞介素-1β(IL-1β)和类胰蛋白酶水平(ELISA法)。
结果:MS组结肠黏膜炎症评分(1.60±0.52)分别高于WA组(0.60±0.70)、CON组(0.50±0.53)(P均<0.05);MS组结肠黏膜肥大细胞数量(6.97±1.12,个/HPF)分别高于WA组(3.79±0.53,个/HPF)、CON组(3.76±0.61,个/HPF)(P均<0.05);MS组结肠粘膜组织孵育上清液IL-1β浓度(22.72±2.63pg/g)也分别高于WA组(13.96±1.34 pg/g)和CON组(13.94±1.71 pg/g)(P均<0.05);MS组上清液类胰蛋白酶浓度(2.99±0.37ng/g)分别高于WA组(1.66±0.27 ng/g)和CON组(1.66±0.33 ng/g)(P均<0.05)。当结肠内气囊压力为40、60、80 mmHg时, MS组和WA组的AWR评分和腹壁肌电幅值明显高于CON组(P均<0.05),而且与上述各项炎症指标存在正相关关系(P均<0.05)。
结论:应激(包括早期、急性应激)可以诱导内脏感觉过敏,早期应激还可诱导肠道低度炎症,这种低度炎症与内脏感觉过敏相关。
AIM: To evaluate the role of stress(early-life stress and acute sterss) on intestinal mucosal inflammation and visceral sensitivity in rats.
METHODS:Thirty-six newborn male Sprague-Dawley(SD) rats were randomly divided into control group(CON,n=12), maternal separation group(MS,n=12) and acute water avoidance group(WA,n=12). The newborn rats in MS were recepted maternal separation between 2~(nd) -21~(st) day postnatal . The rats in WA were recepted a water avoidance at the 60~(th) day. At the 2nd month, abdominal withdrawal reflex (AWR) and myoelectric amplitude (MA) of the oblique externus abdominis muscle were recorded respectively after colonic distention. The colonic tissue samples were collectted for histopathologic examinations and toluidine blue stain, and the contents of IL-1βand tryptase in colon tissue culture supernants were dected by ELISA.
RESULT:The mean mucosal inflammation score in MS(1.60±0.52) was ,significantly higher than in WA(0.60±0.70,P=0.000) and in CON(0.50±0.53,P=0.000).The mast cell numbers in MS(6.97±1.12,cells/HPF) were significantly higher than that in WA(3.79±0.53,P=0.000) and in CON(3.76±0.61,P=0.000) respectively. The content of IL-1βin MS was 22.72±2.63pg/g,significantly higher than in WA (13.96±1.34 pg/g,P=0.001) and CON(13.94±1.71 pg/g,P=0.000). The content of tryptase in MS was 2.99±0.37ng/g,that's significantly higher than in WA(1.66±0.27 ng/g,P=0.000) and CON (1.66±0.33 ng/g,P=0.000).When the balloon pressure was up to 40, 60, 80mmHg respectively, the AWR score and MA in MS and WA were significantly higher than those in CON(all P < 0.05), and these indexes were positively correlated with the mucosal inflammation(P<0.05,respectively ).
CONLUSIONS:The stress(including early-life stress and acute sterss) may activate the visceral sensitivity, and the arly-life stress may induce low grade mucosal inflammation in the colon which may activate the visceral sensitivity.
方法:36只雄性新生SD幼鼠,分为正常对照组(CON,n=12)、母婴分离组(MS,n=12)、急性避水应激组(WA,n=12)。MS组幼鼠出生第2天开始进行母婴分离,持续至出生后第3周。WA组动物于出生后第60天接受避水实验。2月龄时各组大鼠接受直肠气囊扩张大鼠腹部回缩反射(AWR)评分和腹壁肌电测定;结束后取结肠组织作常规病理学检查和肥大细胞计数(甲苯胺蓝染色法)、并测定结肠黏膜孵育上清液白细胞介素-1β(IL-1β)和类胰蛋白酶水平(ELISA法)。
结果:MS组结肠黏膜炎症评分(1.60±0.52)分别高于WA组(0.60±0.70)、CON组(0.50±0.53)(P均<0.05);MS组结肠黏膜肥大细胞数量(6.97±1.12,个/HPF)分别高于WA组(3.79±0.53,个/HPF)、CON组(3.76±0.61,个/HPF)(P均<0.05);MS组结肠粘膜组织孵育上清液IL-1β浓度(22.72±2.63pg/g)也分别高于WA组(13.96±1.34 pg/g)和CON组(13.94±1.71 pg/g)(P均<0.05);MS组上清液类胰蛋白酶浓度(2.99±0.37ng/g)分别高于WA组(1.66±0.27 ng/g)和CON组(1.66±0.33 ng/g)(P均<0.05)。当结肠内气囊压力为40、60、80 mmHg时, MS组和WA组的AWR评分和腹壁肌电幅值明显高于CON组(P均<0.05),而且与上述各项炎症指标存在正相关关系(P均<0.05)。
结论:应激(包括早期、急性应激)可以诱导内脏感觉过敏,早期应激还可诱导肠道低度炎症,这种低度炎症与内脏感觉过敏相关。
AIM: To evaluate the role of stress(early-life stress and acute sterss) on intestinal mucosal inflammation and visceral sensitivity in rats.
METHODS:Thirty-six newborn male Sprague-Dawley(SD) rats were randomly divided into control group(CON,n=12), maternal separation group(MS,n=12) and acute water avoidance group(WA,n=12). The newborn rats in MS were recepted maternal separation between 2~(nd) -21~(st) day postnatal . The rats in WA were recepted a water avoidance at the 60~(th) day. At the 2nd month, abdominal withdrawal reflex (AWR) and myoelectric amplitude (MA) of the oblique externus abdominis muscle were recorded respectively after colonic distention. The colonic tissue samples were collectted for histopathologic examinations and toluidine blue stain, and the contents of IL-1βand tryptase in colon tissue culture supernants were dected by ELISA.
RESULT:The mean mucosal inflammation score in MS(1.60±0.52) was ,significantly higher than in WA(0.60±0.70,P=0.000) and in CON(0.50±0.53,P=0.000).The mast cell numbers in MS(6.97±1.12,cells/HPF) were significantly higher than that in WA(3.79±0.53,P=0.000) and in CON(3.76±0.61,P=0.000) respectively. The content of IL-1βin MS was 22.72±2.63pg/g,significantly higher than in WA (13.96±1.34 pg/g,P=0.001) and CON(13.94±1.71 pg/g,P=0.000). The content of tryptase in MS was 2.99±0.37ng/g,that's significantly higher than in WA(1.66±0.27 ng/g,P=0.000) and CON (1.66±0.33 ng/g,P=0.000).When the balloon pressure was up to 40, 60, 80mmHg respectively, the AWR score and MA in MS and WA were significantly higher than those in CON(all P < 0.05), and these indexes were positively correlated with the mucosal inflammation(P<0.05,respectively ).
CONLUSIONS:The stress(including early-life stress and acute sterss) may activate the visceral sensitivity, and the arly-life stress may induce low grade mucosal inflammation in the colon which may activate the visceral sensitivity.
引文
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[22]Mayer EA,Naliboff BD,Chang L,Coutinho SV. V.Stress and irritable bowel syndrome[J].Am J Physiol Gastrointest Liver Physiol,2001;280(4);519-524. PMID: 11254476
[23]Mayer EA,Berman S,Derbyshire SW,Suyenobu B,Chang L,Fitzgerald L,Mandelkern M,Hamm L,Vogt B,Naliboff BD.The effect of the 5-HT3 receptor antagonist, alosetron, on brain responses to visceral stimulation in irritable bowel syndrome patients.Aliment Pharmacol Ther.2002;16(7):1357-1366. PMID: 12144587
[24] Dickhaus B,Mayer EA,Firooz N,Stains J,Conde F,Olivas TI,Fass R,Chang L,Mayer M,Naliboff BD.Irritable bowel syndrome patients show enhanced modulation of visceral perception by auditory stress[J].Am J Gastroenterol. 2003;98(1):135-43 .PMID: 12526949
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