Leng Yu-xin, Wei Yan-yu, Zhou Shu-pei, Duan Li-ping
Department of Gastroenterology, Third Hospital, Peking University, Beijing, China.
Zhonghua Yi Xue Za Zhi. 2009 Nov 17;89(42):2992-6.
To establish the irritable bowel syndrome (IBS) rat model by the combination of acute stress and transient intestinal infection with Trichinella spiralis (T.S.).
The rat model of acute cold restraint stress post-infection (PI + ACRS) was established as following: the intestinal infection with 1500 T.S. in 1 ml saline to adult male BN rats was performed at Day 0 by gastric lavage. Then a 2-hour stimulus of ACRS was administered at Day 100. Age matched transiently infected without stress rats (PI) and normal rats served as controls (CON) (n = 6, for each). After anesthesia, all the rats underwent colonic manometry in vivo at Day 100. The colonic pressures at 3 different states (baseline for 20 min; 1 ml balloon distension stimulation for 5 min and 2 ml balloon distension stimulation for 20 min) were traced with a 5-minute interval between each two. The following parameters were recorded: (1) Duration (Dur.): total time of contractions during each state. (2) Maximum (Max.): highest amplitude of constructional waves (mm Hg). (3) Area: area under contraction waves. (4) Number (Num.): frequencies of contraction wave during each state. The visceromoter response to colorectal distension (CRD) was analyzed at Day 100 post-infection. And the distension volume of AWR 3 was detected for 5 times with a 20-min interval in each rat.
The histological damage of intestine induced by T.S. infection is transient. Although such acute infectious features as epithelial edema, hyperemia and marked eosinophil infiltration appeared at Day 10 PI, the histological changes almost recovered at Day 100 PI in both the PI group and the PI + ACRS group. Both the stimuli of transient infection and the ACRS post-infection induced intestinal dysmotility and visceral hypersensitivity. The ACRS post infection further worsened the transiently induced infection. The parameters of Num, Max and Area in the PI + ACRS group were all significantly higher than those of the PI group [Max: (41 +/- 17) mm Hg vs (22 +/- 6) mm Hg, P = 0.000; Area: (7693 +/- 2822) mm Hg.s vs (5092 +/- 1687) mm Hgxs, P = 0.000; Num: 9.5 +/- 2.6 vs 6.6 +/- 3.1, P = 0.000]; so was the distension volume of AWR3 [(2.25 +/- 0.29) ml vs (2.52 +/- 0.32) ml, P = 0.004]. As compared with the range of normal values from controls, the abnormality rates of motility parameters and visceral threshold in PI + ACRS group also had an larger increment than those of the PI group (PI + ACRS: 50.0% - 87.5% and 100% respectively, PI: 25.0% - 37.5% and 90.0% respectively).
The pathophysiological changes in the PI + ACRS rats are consistent with those of IBS. Aggravated by psychological factors, these rats reproduce the symptoms of intestinal dysmotility and visceral hypersensitivity. A proper animal model has been established for the investigation of IBS.
通过急性应激与旋毛虫(T.S.)短暂肠道感染相结合的方法建立肠易激综合征(IBS)大鼠模型。
按照以下步骤建立感染后急性冷束缚应激(PI + ACRS)大鼠模型:于第0天通过灌胃给成年雄性BN大鼠接种1500条旋毛虫(溶于1 ml生理盐水中)。然后在第100天给予2小时的急性冷束缚应激刺激。将年龄匹配的未受应激的短暂感染大鼠(PI)和正常大鼠作为对照(CON)(每组n = 6)。在第100天麻醉后,所有大鼠进行活体结肠测压。记录结肠在3种不同状态下(20分钟基线状态;1 ml气囊扩张刺激5分钟;2 ml气囊扩张刺激20分钟)的压力,每两种状态之间间隔5分钟。记录以下参数:(1)持续时间(Dur.):每种状态下收缩的总时间。(2)最大值(Max.):收缩波的最高幅度(毫米汞柱)。(3)面积:收缩波下的面积。(4)次数(Num.):每种状态下收缩波的频率。在感染后第100天分析对结直肠扩张(CRD)的内脏运动反应。并在每只大鼠中以20分钟的间隔检测5次AWR3的扩张体积。
旋毛虫感染所致的肠道组织学损伤是短暂的。虽然在感染后第10天出现了上皮水肿、充血和明显的嗜酸性粒细胞浸润等急性感染特征,但在感染后第100天,PI组和PI + ACRS组的组织学变化几乎都恢复了。短暂感染刺激和感染后急性冷束缚应激均诱导肠道运动障碍和内脏高敏感性。感染后急性冷束缚应激进一步加重了短暂诱导的感染。PI + ACRS组的Num、Max和面积参数均显著高于PI组[Max:(41±17)毫米汞柱对(22±6)毫米汞柱,P = 0.000;面积:(7693±2822)毫米汞柱·秒对(5092±1687)毫米汞柱·秒,P = 0.000;Num:9.5±2.6对6.6±3.1,P = 0.000];AWR3的扩张体积也是如此[(2.25±0.29)ml对(2.52±0.32)ml,P = 0.004]。与对照组的正常范围值相比,PI + ACRS组的运动参数异常率和内脏阈值的异常率也比PI组有更大幅度的增加(PI + ACRS组分别为50.0% - 87.5%和100%,PI组分别为25.0% - 37.5%和90.0%)。
PI + ACRS大鼠的病理生理变化与肠易激综合征一致。受心理因素影响,这些大鼠重现了肠道运动障碍和内脏高敏感性症状。已建立了一种合适的动物模型用于肠易激综合征的研究。