多器官功能障碍综合征肠神经—Cajal间质细胞—平滑肌网络形态学变化及大承气汤治疗作用
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摘要
背景:多器官功能障碍综合症(multiple organ dysfunction syndrome, MODS)是腹部外科患者死亡的重要原因,以高代谢、高动力循环状态、过度失控的炎症反应和器官功能障碍为特征的临床综合征。胃肠道被认为是促发全身炎症反应综合征(systemic inflammation response syndrome, SIRS)和MODS的始动器官与靶部位,胃肠功能状态被认为是判断危重病人预后的一项重要指标。促进胃肠运动功能的恢复是有效地阻断MODS向多器官衰竭(multiple organ failure, MOF)发展的有效手段。胃肠道Cajal间质细胞(interstitial cells of Cajal, ICC)形成网络状结构广泛分布于胃肠道各肌层。ICC按照功能分为重要的两种:肌间ICC(ICC-MY),是胃肠慢波(slow wave, SW)活动的起搏器和传导者,具有基本节律起搏和传播功能;深部肌间神经丛ICC(ICC-DMP),是肠神经作用的首要靶细胞,肠神经释放的递质主要是通过ICC-DMP来调节胃肠动力。ICC作为信息整合中转站,参与肠神经系统(enteric nerve system,ENS)信号向平滑肌细胞(smooth muscle cells,SMC)的传送,从而在胃肠动力的发生与调控中起重要作用,同时ENS运动末梢、肌间丛ICC、SMC相互联系形成网络,构成胃肠动力基本功能单位(basic functional unit of gastrointestinal motility,BFUGM)。ICC在肠神经向平滑肌的信号传导中起重要的中介作用,肠神经-ICC-平滑肌网络与胃肠运动功能障碍密切相关。
目的:本实验以细菌性腹膜炎致MODS大鼠模型为研究对象,观察MODS大鼠模型小肠神经-ICC-平滑肌网络的形态学变化以及大承气汤(Da-Cheng-Qi Decoction, DCQD)治疗的影响,探讨MODS致胃肠运动障碍的产生机制和大承气汤治疗MODS机理。
方法:健康成年Wistar大鼠100只,雌雄各半,体重200g-250g,随机分组如下:对照组(20只)、MODS模型组(40只)和DCQD治疗组(40只)。对照组每只动物予腹腔注射1ml生理盐水。MODS模型组和DCQD治疗组每只动物予腹腔注射1ml E.coloi.混悬液,建立细菌性腹膜炎致MODS模型。DCQD治疗组于造模当日即给予DCQD灌胃,2次/日,每次1ml/100g。造模24小时后取存活大鼠上段小肠组织制作肠肌层全厚组织标本,进行c-Kit和囊泡装乙酰胆碱转运体(VAChT)/神经型一氧化氮合酶(nNOS)免疫荧光双标记染色后用于激光扫描共聚焦显微镜检测、分析;制作电镜标本用于透射电镜观测。
结果:
①大体标本:较之对照组,MODS组大鼠胃肠极度扩张,胃肠梗阻征象明显;DCQD治疗组胃肠扩张、梗阻较MODS组明显减轻。
②共聚焦显微镜检测ICC-DMP网络:与对照组相比,MODS组大鼠ICC-DMP数量明显减少(p<0.01),ICC突触的数量减少,相互间的连接不连续,完整的网络样结构消失,细胞荧光强度减弱(p<0.01);DCQD治疗组大鼠ICC-DMP数量比MODS组有所增多(p<0.01),ICC-DMP突触增多,相互保持联系,基本保持网络状结构,细胞的荧光强度比MODS组有所增强(p<0.01)。
③共聚焦显微镜检测肠神经-ICC网络:与对照组相比,MODS组大鼠ICC-DMP数量明显减少(p<0.01),突触的数量减少,完整的网络样结构消失,细胞荧光强度减弱(p<0.01);胆碱能/氮能神经神经纤维明显减少(p<0.01/p<0.01)),神经网结构紊乱,彼此间的连接减少,神经网络的荧光强度减弱(p<0.01/p<0.01));ICC与肠神经纤维两者间失去紧密连接,肠神经-ICC网络的完整结构受到破坏。DCQD治疗组大鼠ICC-DMP数量比MODS组有所增多(p<0.01),保持网络状结构,细胞的荧光强度比MODS组有所增强(p<0.01);胆碱能/氮能神经纤维较MODS组多(p<0.01/p<0.01)),维持神经网络样结构,神经节之间的连接较MODS组增多,荧光强度有所增强(p<0.01/p<0.01));ICC与肠神经纤维之间维持连接,肠神经-ICC网络保持连续。
④透射电镜观测ICC-DMP超微结构:MODS组ICC-DMP细胞核皱缩,胞浆内细胞器数量明显减少,结构出现异常,基底膜缺乏或不完整,超微结构受损明显。较之MODS组,DCQD治疗组ICC-DMP细胞核形态基本正常,胞浆内细胞器数量较多,形态结构较为清楚,基底膜基本完整,超微结构较MODS组损伤明显减轻。
⑤透射电镜观测肠神经-ICC-平滑肌网络的超微结构:与对照组相比,MODS组ICC-DMP细胞突起明显减少或消失,相互间的缝隙连接缺失;ICC-DMP与神经纤维间的突触样连接缺如,间距增加;ICC-DMP相互间及其与平滑肌细胞间缝隙连接消失,存在较大间隙;神经-ICC-平滑肌网络的形态学基础受到明显破坏。较之MODS组,DCQD治疗组部分ICC-DMP细胞突起减少,细胞突起损伤不明显;相互间保持连接;ICC-DMP与神经纤维间保持突触样连接;ICC-DMP与平滑肌细胞间存在缝隙连接,无明显间隙;基本保持神经-ICC-平滑肌网络结构的完整。
结论:①细菌性腹膜炎致MODS组大鼠胃肠极度扩张,胃肠梗阻征象明显;DCQD治疗能够显著改善胃肠麻痹梗阻征。
②MODS时,ICC-DMP网络受到破坏,ICC-DMP超微结构受到损伤;DCQD治疗可维持MODS状态下ICC-DMP网络结构,减轻ICC-DMP超微结构的损伤。
③MODS时,小肠胆碱能/氮能神经和ICC-DMP数量减少,肠神经-ICC网络结构受到破坏; DCQD治疗能够增加神经、ICC的细胞数量,维持肠神经-ICC网络结构的完整。
④MODS时,肠神经、ICC-DMP和平滑肌三者间相互连接的超微结构受到损伤,肠神经-ICC-平滑肌细胞网络的超微结构被破坏;DCQD治疗能够减轻肠神经、ICC和平滑肌三者间相互连接间的超微结构的损伤,维持肠神经-ICC-平滑肌细胞网络形态学基础的完整性。
Background: Multiple organ dysfunction syndrome (MODS) is the main cause of the death of patients with abdominal surgical diseases, which characterized with hyper-metabolizability, hyper-circulation, immoderate and out of controlled inflammatory response and organ dysfunction. The gastrointestinal tract is considered to be the key organ to originate and to trigger systemic inflammation response syndrome (SIRS) and MODS, and the condition of gastrointestinal motility is also thought to be the criterion of evaluation the prognosis of severely injured patients. Improving the recovery of gastrointestinal motility function could effectively prevent MODS from deteriorating to multiple organ failure (MOF). Interstitial cells of Cajal (ICC) show a highly branched morphology and form unique networks in gastrointestinal tract which coordinate gastrointestinal motility. Two populations of ICC are known by their functions: one located in the area of the myenteric plexus (ICC-MY), which form a network between the circular and longitudinal muscle layers, and serve as electrical pacemakers; the other in the area of the deep muscular plexus (ICC-DMP), which lies between the outer and the inner subdivisions of the circular muscle layer, and are densely innervated by excitatory and inhibitory enteric motor neurons. These ICCs form the enteric nerve-ICC-smooth muscle cells network associated with the varicosities of enteric motor neuron and have close association with the smooth muscle cells through gap junctions. As a unique unity, enteric nerve-ICC-smooth muscle cells network is considered to be related to the gastrointestinal dysmitility in many diseases.
Objective: To observe the morphological changes of enteric nerve- ICC-smooth muscle cells network in rats with MODS, and to investigate the therapeutic effects of Da-Cheng-Qi Decoction (DCQD).
Methods: One handred Wistar rats of both sexes weighing 200 to 250g were randomly divided into three groups:control group(n=20), MODS group (n=40)and DCQD treated group(n=40). The model of MODS was established according to previous study. Briefly, 1 ml suspension of 8 x 108cfu/ml of Escherichia coli strain O127 H6, which contained 10% BaSO4, was injected under sterile conditions into the abdominal cavity of the rats in the MODS and DCQD group. The rats of control group were injected 1ml of normal saline. The rats of DCQD treated group were administrated by gavage with DCQD (twice a day) after the suspension was injected. Twenty-four hours after injection, the proximal 10cm segment of jejunum beginning 2cm distal to the pylorus from each group, was studied using c-Kit and vesicular acetylcholine transporter (VAChT)/ neuronal nitric oxide synthase (nNOS) immunohistochemical double-staining with whole-mount preparation technique and confocal laser scanning microscopy and transmission electron microscope.
Results:
1. Anatomical changes: Compared with those in control group, the gastrointestinal tracts were distended significantly in the rats with MODS; Compared with the MODS group, the distention was markedly alleviated in DCQD group.
2. Immunohistochemistry: (1) Compared with the control group, the distributions and densities of ICC-DMP of intestine in MODS group were significantly decreased (P<0.01), the ICC-DMP network was disrupted. After treatment with DCQD, the ICC-DMP network was significantly recovered. Compared with MODS group, the distributions and densities of ICC-DMP of intestine in DCQD group were significantly increased (P<0.01). (2)Compared the MODS group with the control group, the distributions and densities of cholinergic nerves (P<0.01)/ nitrergic nerves (P<0.01) and ICC-DMP (P<0.01) of intestine were significantly decreased respectively, the network of cholinergic/nitrergic nerve-ICC was disrupted. After treatment with DCQD, the damage in network of cholinergic nerve/ nitrergic-ICC were significantly recovered. Compared with MODS group, the distributions and densities of cholinergic nerves (P<0.01)/ Nitrergic nerves (P<0.01) and ICC-DMP (P<0.01) of intestine were significantly increased respectively.
3. Electron microscopy: (1) Compared the ultrastructural features of ICC-DMP of the MODS group with the control group, ICC-DMP displayed severe ultrastructural abnormalities. Injury was displayed in both the perinuclear cytoplasm and the ICC-DMP processes; the nuclei of ICC-DMP were shrunken, and the plasma membrane bleb was observed. Compared the ultrastructural features of ICC-DMP of the DCQD group with the MODS group, the shape of ultrastructural features of ICC-DMP were better than the MODS group, the nuclei was nearly normal. (2) Compared the ultrastructural features of intestinal nerve-ICC-smooth muscle cells network of the MODS group with the control group, the ultrastructural features of ICC-DMP, nerve, smooth muscle cells were severely damaged, the gap junction between ICC-DMP and neighbor smooth muscle cells and the other ICC was enhanced or disappeared, the synaptic-like contact between the varicosities of nerve and ICC-DMP was discontinued. Compared the ultrastructural features of intestinal nerve-ICC-smooth muscle cells network of the DCQD group with the MODS group, the ultrastructural features of ICC-DMP, nerve, smooth muscle cells were significantly recovered, the gap junction between ICC-DMP and neighbor smooth muscle cells and the other ICC could be visualized, the synaptic-like contact between the varicosities of nerve and ICC-DMP was reappeared.
Conclusions: (1) Gross morphological observation of the gastrointestinal tracts revealed a marked intestinal distention in the rats with MODS; this distention was due to the paralysis of gastrointestinal tracts. DCQD could alleviate the distention significantly. (2) ICC-DMP network was severely damaged and the ultrastructural features of ICC-DMP were injured in rats with MODS. DCQD could protect the ultrastructural features of ICC-DMP and maintain the ICC-DMP network. (3) The number of ICC-DMP, cholinergic nerves and nitrergic nerves were reduced in MODS, the enteric nerve-ICC network was damaged significantly. DCQD could enhance the number of the ICC-DMP, cholinergic nerves and nitrergic nerves, and repair the enteric nerve-ICC network. (4)The ultrastructural features between ICC-DMP and smooth muscle cells, ICC-DMP and terminal nerve were damaged significantly in MODS, and the enteric nerve-ICC-smooth muscle cells network was discontinued. DCQD could protect the ultrastructural features, and restore the enteric nerve-ICC- smooth muscle cells network.
目的:本实验以细菌性腹膜炎致MODS大鼠模型为研究对象,观察MODS大鼠模型小肠神经-ICC-平滑肌网络的形态学变化以及大承气汤(Da-Cheng-Qi Decoction, DCQD)治疗的影响,探讨MODS致胃肠运动障碍的产生机制和大承气汤治疗MODS机理。
方法:健康成年Wistar大鼠100只,雌雄各半,体重200g-250g,随机分组如下:对照组(20只)、MODS模型组(40只)和DCQD治疗组(40只)。对照组每只动物予腹腔注射1ml生理盐水。MODS模型组和DCQD治疗组每只动物予腹腔注射1ml E.coloi.混悬液,建立细菌性腹膜炎致MODS模型。DCQD治疗组于造模当日即给予DCQD灌胃,2次/日,每次1ml/100g。造模24小时后取存活大鼠上段小肠组织制作肠肌层全厚组织标本,进行c-Kit和囊泡装乙酰胆碱转运体(VAChT)/神经型一氧化氮合酶(nNOS)免疫荧光双标记染色后用于激光扫描共聚焦显微镜检测、分析;制作电镜标本用于透射电镜观测。
结果:
①大体标本:较之对照组,MODS组大鼠胃肠极度扩张,胃肠梗阻征象明显;DCQD治疗组胃肠扩张、梗阻较MODS组明显减轻。
②共聚焦显微镜检测ICC-DMP网络:与对照组相比,MODS组大鼠ICC-DMP数量明显减少(p<0.01),ICC突触的数量减少,相互间的连接不连续,完整的网络样结构消失,细胞荧光强度减弱(p<0.01);DCQD治疗组大鼠ICC-DMP数量比MODS组有所增多(p<0.01),ICC-DMP突触增多,相互保持联系,基本保持网络状结构,细胞的荧光强度比MODS组有所增强(p<0.01)。
③共聚焦显微镜检测肠神经-ICC网络:与对照组相比,MODS组大鼠ICC-DMP数量明显减少(p<0.01),突触的数量减少,完整的网络样结构消失,细胞荧光强度减弱(p<0.01);胆碱能/氮能神经神经纤维明显减少(p<0.01/p<0.01)),神经网结构紊乱,彼此间的连接减少,神经网络的荧光强度减弱(p<0.01/p<0.01));ICC与肠神经纤维两者间失去紧密连接,肠神经-ICC网络的完整结构受到破坏。DCQD治疗组大鼠ICC-DMP数量比MODS组有所增多(p<0.01),保持网络状结构,细胞的荧光强度比MODS组有所增强(p<0.01);胆碱能/氮能神经纤维较MODS组多(p<0.01/p<0.01)),维持神经网络样结构,神经节之间的连接较MODS组增多,荧光强度有所增强(p<0.01/p<0.01));ICC与肠神经纤维之间维持连接,肠神经-ICC网络保持连续。
④透射电镜观测ICC-DMP超微结构:MODS组ICC-DMP细胞核皱缩,胞浆内细胞器数量明显减少,结构出现异常,基底膜缺乏或不完整,超微结构受损明显。较之MODS组,DCQD治疗组ICC-DMP细胞核形态基本正常,胞浆内细胞器数量较多,形态结构较为清楚,基底膜基本完整,超微结构较MODS组损伤明显减轻。
⑤透射电镜观测肠神经-ICC-平滑肌网络的超微结构:与对照组相比,MODS组ICC-DMP细胞突起明显减少或消失,相互间的缝隙连接缺失;ICC-DMP与神经纤维间的突触样连接缺如,间距增加;ICC-DMP相互间及其与平滑肌细胞间缝隙连接消失,存在较大间隙;神经-ICC-平滑肌网络的形态学基础受到明显破坏。较之MODS组,DCQD治疗组部分ICC-DMP细胞突起减少,细胞突起损伤不明显;相互间保持连接;ICC-DMP与神经纤维间保持突触样连接;ICC-DMP与平滑肌细胞间存在缝隙连接,无明显间隙;基本保持神经-ICC-平滑肌网络结构的完整。
结论:①细菌性腹膜炎致MODS组大鼠胃肠极度扩张,胃肠梗阻征象明显;DCQD治疗能够显著改善胃肠麻痹梗阻征。
②MODS时,ICC-DMP网络受到破坏,ICC-DMP超微结构受到损伤;DCQD治疗可维持MODS状态下ICC-DMP网络结构,减轻ICC-DMP超微结构的损伤。
③MODS时,小肠胆碱能/氮能神经和ICC-DMP数量减少,肠神经-ICC网络结构受到破坏; DCQD治疗能够增加神经、ICC的细胞数量,维持肠神经-ICC网络结构的完整。
④MODS时,肠神经、ICC-DMP和平滑肌三者间相互连接的超微结构受到损伤,肠神经-ICC-平滑肌细胞网络的超微结构被破坏;DCQD治疗能够减轻肠神经、ICC和平滑肌三者间相互连接间的超微结构的损伤,维持肠神经-ICC-平滑肌细胞网络形态学基础的完整性。
Background: Multiple organ dysfunction syndrome (MODS) is the main cause of the death of patients with abdominal surgical diseases, which characterized with hyper-metabolizability, hyper-circulation, immoderate and out of controlled inflammatory response and organ dysfunction. The gastrointestinal tract is considered to be the key organ to originate and to trigger systemic inflammation response syndrome (SIRS) and MODS, and the condition of gastrointestinal motility is also thought to be the criterion of evaluation the prognosis of severely injured patients. Improving the recovery of gastrointestinal motility function could effectively prevent MODS from deteriorating to multiple organ failure (MOF). Interstitial cells of Cajal (ICC) show a highly branched morphology and form unique networks in gastrointestinal tract which coordinate gastrointestinal motility. Two populations of ICC are known by their functions: one located in the area of the myenteric plexus (ICC-MY), which form a network between the circular and longitudinal muscle layers, and serve as electrical pacemakers; the other in the area of the deep muscular plexus (ICC-DMP), which lies between the outer and the inner subdivisions of the circular muscle layer, and are densely innervated by excitatory and inhibitory enteric motor neurons. These ICCs form the enteric nerve-ICC-smooth muscle cells network associated with the varicosities of enteric motor neuron and have close association with the smooth muscle cells through gap junctions. As a unique unity, enteric nerve-ICC-smooth muscle cells network is considered to be related to the gastrointestinal dysmitility in many diseases.
Objective: To observe the morphological changes of enteric nerve- ICC-smooth muscle cells network in rats with MODS, and to investigate the therapeutic effects of Da-Cheng-Qi Decoction (DCQD).
Methods: One handred Wistar rats of both sexes weighing 200 to 250g were randomly divided into three groups:control group(n=20), MODS group (n=40)and DCQD treated group(n=40). The model of MODS was established according to previous study. Briefly, 1 ml suspension of 8 x 108cfu/ml of Escherichia coli strain O127 H6, which contained 10% BaSO4, was injected under sterile conditions into the abdominal cavity of the rats in the MODS and DCQD group. The rats of control group were injected 1ml of normal saline. The rats of DCQD treated group were administrated by gavage with DCQD (twice a day) after the suspension was injected. Twenty-four hours after injection, the proximal 10cm segment of jejunum beginning 2cm distal to the pylorus from each group, was studied using c-Kit and vesicular acetylcholine transporter (VAChT)/ neuronal nitric oxide synthase (nNOS) immunohistochemical double-staining with whole-mount preparation technique and confocal laser scanning microscopy and transmission electron microscope.
Results:
1. Anatomical changes: Compared with those in control group, the gastrointestinal tracts were distended significantly in the rats with MODS; Compared with the MODS group, the distention was markedly alleviated in DCQD group.
2. Immunohistochemistry: (1) Compared with the control group, the distributions and densities of ICC-DMP of intestine in MODS group were significantly decreased (P<0.01), the ICC-DMP network was disrupted. After treatment with DCQD, the ICC-DMP network was significantly recovered. Compared with MODS group, the distributions and densities of ICC-DMP of intestine in DCQD group were significantly increased (P<0.01). (2)Compared the MODS group with the control group, the distributions and densities of cholinergic nerves (P<0.01)/ nitrergic nerves (P<0.01) and ICC-DMP (P<0.01) of intestine were significantly decreased respectively, the network of cholinergic/nitrergic nerve-ICC was disrupted. After treatment with DCQD, the damage in network of cholinergic nerve/ nitrergic-ICC were significantly recovered. Compared with MODS group, the distributions and densities of cholinergic nerves (P<0.01)/ Nitrergic nerves (P<0.01) and ICC-DMP (P<0.01) of intestine were significantly increased respectively.
3. Electron microscopy: (1) Compared the ultrastructural features of ICC-DMP of the MODS group with the control group, ICC-DMP displayed severe ultrastructural abnormalities. Injury was displayed in both the perinuclear cytoplasm and the ICC-DMP processes; the nuclei of ICC-DMP were shrunken, and the plasma membrane bleb was observed. Compared the ultrastructural features of ICC-DMP of the DCQD group with the MODS group, the shape of ultrastructural features of ICC-DMP were better than the MODS group, the nuclei was nearly normal. (2) Compared the ultrastructural features of intestinal nerve-ICC-smooth muscle cells network of the MODS group with the control group, the ultrastructural features of ICC-DMP, nerve, smooth muscle cells were severely damaged, the gap junction between ICC-DMP and neighbor smooth muscle cells and the other ICC was enhanced or disappeared, the synaptic-like contact between the varicosities of nerve and ICC-DMP was discontinued. Compared the ultrastructural features of intestinal nerve-ICC-smooth muscle cells network of the DCQD group with the MODS group, the ultrastructural features of ICC-DMP, nerve, smooth muscle cells were significantly recovered, the gap junction between ICC-DMP and neighbor smooth muscle cells and the other ICC could be visualized, the synaptic-like contact between the varicosities of nerve and ICC-DMP was reappeared.
Conclusions: (1) Gross morphological observation of the gastrointestinal tracts revealed a marked intestinal distention in the rats with MODS; this distention was due to the paralysis of gastrointestinal tracts. DCQD could alleviate the distention significantly. (2) ICC-DMP network was severely damaged and the ultrastructural features of ICC-DMP were injured in rats with MODS. DCQD could protect the ultrastructural features of ICC-DMP and maintain the ICC-DMP network. (3) The number of ICC-DMP, cholinergic nerves and nitrergic nerves were reduced in MODS, the enteric nerve-ICC network was damaged significantly. DCQD could enhance the number of the ICC-DMP, cholinergic nerves and nitrergic nerves, and repair the enteric nerve-ICC network. (4)The ultrastructural features between ICC-DMP and smooth muscle cells, ICC-DMP and terminal nerve were damaged significantly in MODS, and the enteric nerve-ICC-smooth muscle cells network was discontinued. DCQD could protect the ultrastructural features, and restore the enteric nerve-ICC- smooth muscle cells network.
引文
1.甘枚,梁建新。多器官功能障碍综合征的进展。医学综述。2006;l2:862-865
2.岳茂兴。腹部外科疾病并发多器官功能障碍综合征代谢特点及分阶段营养支持治疗。中国危重病急救医学。2003;15:29-31
3.张趣,刘春峰。胃肠道与SIRS和MOD日本医学介绍,2005;26:281-283
4.王晓梅,董云,王一平。MODS与胃肠道关系。中华腹部疾病杂志,2003;3:379-340
5. Gregory M,Swank MD,Edwin A,ct a1.Role ofthe Gut in multiple organ failure:Bacterial translecation and penneablility changes.World J surg,1996;20:411-417
6. Tokyay R, Zeigler ST,Heggers JP,et a1.Efects of anesthesia,surgery fluid resuscitation and endotoxln administration on postbum bacterial translecation.J Trauma.1991;31:1376-1379
7. Hassoun HT,Kone BC,Mercer DW,et a1. Postinjury multiple organfailure:the role of the gut.Shock.2001;15(1):l-7
8.孟宪均.多器官功能障碍综合征研究展望.中华医学杂志,1998;78(6):407-408
9. Matejovie M,Rokyta R Jr,Kromecky A,et a1.Gastroitestinal tract dysfunction in critical illness.Gas Lek Cesk,2002;141(2):46-50
10. Ward SM, Sanders KM, Hirst GDS. Role of interstitial cells of Cajal in neural control of gastrointestinal smooth muscles. Neurogastroenterol Motil, 2004;16 (Suppl.1):112–117
11. Daniel EE. Communication between interstial cells of Cajal and gsstrointestinal mnscle. Neurogastroenterol Motil, 2004;16 (1):118-122
12. Hanani M, Freund HR. Interstitial cells of Cajal—their role in pacing and signal transmission in the digestive system. Acta Physiol Scand,2000;170(3):177-190
13. Wang XY, Paterson C, Huizinga JD. Cholinergic and nitrergic innervation of ICC-DMP and ICC-IM in the human small intestine. Neurogastroenterol motil. 2003;15:531-543
14. Huizinga JD, Ambrous K, Der-Silaphet TD: Co-operation between neural and myogenic mechanisms in the control of distension-induced peristalsis in the mouse small intestine. J Physiol (Lond) 1998;506:843–856
15. Wang XY, Sanders KM, Ward SM. Intimate relationship between interstitial cells of Cajal and enteric nerves in the guinea-pig small intestine. Cell TissueRes,1999;295:247-256
16. Laszlo Nemth, Peter Nemth, Edit Oszlacs, et al. C-kit positive cellular network on normal human bowel and in motility disorders. Acta Biol Szeged, 2001;45(1-4):57-64
17. Takayama I, Horiguchi K, Daigo Y, et al. The interstitial cells of Cajal and a gastroenteric pacemaker system. Arch Histol Cytol,2002;65:1-26
18. Epperson A,Hatton WJ,Callaghan B et al. Molecular components expressed in cultured and freshly isolated interstitial cells of Cajal. Am J Physiol 2000;279:C529-G539
19. Horiguchi K, Sanders KM, Ward SM. Enteric motor neurons form synaptic-like junctions with interstitial cells of Cajal in the canine gastric antrum. Cell Tissue Res,2003;311:299–313
20. Iion S, Ward SM, Sanders KM. Interstitial cells of Cajal are functiongal innervated by excitatory motor neurons in the murine intestine. J Physiol, 2004;556(2):521-530
21. Ward SM , Beckett EAH, Wang XY, et al. Interstitial cells of Cajal mediate cholinergic neurotransmission from enteric motor neurons. J Neurosci,2000;20(4):1393–1403
22. Wang XY, Sanders KM, Ward SM. Relationship between interstitial cells of Cajal and enteric motor neurons in the murine proximal colon. Cell Tissue Res, 2000;302:331–342
23. Takayama I, Daigao Y, Ward SM, et al. Differential gene expression in the small intestines of wild type and W/WV mice. Neurogastroenterol Motil, 2001;13:163-168
24. He CL, Burgart L, Wang L, et al. Decreased interstitial cells of Cajal volume in patients with slow-transit constipation. Gastroenterology, 2000;118:14-21
25. Ordog T, Ward SM, Sanders KM. Interstitial cells of Cajal generate electrical slow waves in the murine stomach, J Physiol, 1999;518,(Pt 1): 257-269
26. Dickens EJ, Edwards FR, Hirst GD. Selective knockout of intramuscular interstitial cells reveals their roles in the generation of slow waves oin mouse stomach. J Physiol, 2001;531,(Pt 3): 827-833
27. Tadayoshi Takeuchi,Kaori Fujinami,Yutaka Okishio. Essential role of the interstitial cells of Cajal in Nitric Oxide-Mediated relaxation of longitudinal muscle of the mouse ileum. J Pharmacol Sci. 2004;95:71-80
28. Toma H, Nakamura K, Emson PC, et al. Immunohistochenical distribution of C-kit-positive cells and nitric oxide synthase-positive nerves in the guinea-pig small intestine. J Auton Nerv Syst,1999; 75:93-99
29. Wang XY, Berezin I, Mikkelsen HB, et al. Pathology of interstitial cells of Cajal in relation to inflammation revealed by ultrastructure but not immunohistochemistry. Am J Pathol,2002; 160(4):1529-1540
30.刘勇,齐清会。多器官功能障碍综合征胃肠动力障碍与Cajal间质细胞关系及大承气冲剂治疗机理。2004,天津医科大学博士研究生学位论文。
31. Sanders KM, Ordog T, Koh SD. et al. Development and plasticity of interstitial cells of Cajal. Neurogastroenterol. Mot,1999; 11:311-338
32、Torihashi S, Ward SM, Nishikawa S-I, et al. C-kit-dependent development of interstitial cells and electrical activity in the murine gastrointestinal tract. Cell Tissue Res,1995; 280:97–111
32. Ward SM, Burns AJ, Torihashi S, et al. Mutation of the proto-oncogene c-kit blocks development of interstitial cells and electrical rhythmicity in murine intestine. J Physiol,1994; 480:91–97
33. Huizinga JD, Thuneberg L, Kluppel M, et al. W/kit gene required for interstitial cells of Cajal and for interstitial pacemaker activity. Nature,1995; 373:347-349
34. Pluja L, Alberti E, Fernandez E, Mikkelsen HB, et al. Evidence supporting presence of two pacemakers in rat colon. Am J Physiol Gastrointest Liver Physiol, 2001; 281(1):G255-G266
35. Nemeth L,Puri P. Three-dimensinal morphology of C-Kit-positive cellular network and nitrergic innervation in the human gut. Arch Pathol Leb Med. 2001;125:899-904
36.李丽,多器官功能障碍综合征炎症机制的研究进展现代诊断与治疗。2003; 14(3):164-166
37. Strieter RM, Kumkel SL, Bone RC. Role of tumor necrosis factor-αin disease states and inflammation. Crit Care Med, 1993; 2l (10Supp1): S447-463.
38. Fong Y, Lowrg SF. Tumor necrosis factor in the pathophysiology of infection and sepsis, Clin Immunol Immunopathol, 1990; 55(2):l57-170.
39.朱正华,曹祥龙,熊利泽。炎性免疫细胞凋亡在SIRS和MODS中的作用。中国危重病急救医学,1999; l1:507-509
40.黄重敏,陆富刚,MODS免疫发病机制的研究进展,中国急救医学,2002,22:739-740
41. Ward SM, Ordog T, Koh SD, et al. Pacemaking in interstitial cells of Cajal depends upon calcium handing by endoplasmic reticulum and mitochondria, J Physiol (Lond), 2000; 525:355-361
42. Liu X, Kim CN, Yang J, et al. Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell, 1996; 86:147-157
43. Lu G, Qian X, Berezin I, et al. Imflammation modulates in vitro colonic myoelectric and contractive activity and interstitial cells of Cajal. Am J Physiol,1997; 273(6 Pt 1): G1233-G1245
44. Huizinga JD. Neural injury, repair, and adaptation in the GI tract. IV. Pathophysiology of GI motility relaed to interstitial cells of Cajal. Am J Physiol,1998; 275(Pt 1):G381-G386
45. Ekblad E, Sjuve R, Arner A, Sundler F. Enteric neuroal plasticity and a reduced number of interstitial cells of Cajal in hypertrophic rat ileum, Gut, 1998: Jun;42(6):836-844
46. Altdorfer K, Bagameri G, Donath T, et al. Nitric oxide synthase immunoreactivity of interstitial cells of Cajal in experimental colitis. Inflamm Res,2002; 51:569-571
47. Der T, Bercik P, Donnelly G, et al. Interstitial cells of Cajal and inflammation- induced motor dysfunction in the mouse small intestine. Gastroenterology, 2000; 119(6):1590-1599
48. Nemeth L, Fourcade L, Puri P. Marked morphological differences in the myenteric plexus between the mesenteric and antimesenteric sides of small bowel in premature infants. J Pediatr Surg, 2000; 35(5): 748-752.
49. Kobayashi H, Li Z, Yamataka A, et a1. Acetylcholinesterase distribution and refractory constipation-a new criterion for diagnosis and management. Pediatr surg Int, 2002; 18(5-6): 349-353.
50. Dinah TG, Scott LV, Brady D, et a1. Altered hypothalamie cholinergie responses in patients with nonulcer dyspepsia: a study of pyridostigmine- stimulated growth hormone release. Am J Gastroenterol, 2002; 97 (8):1937-1940.
51. Suzuki H, Ward SM, Bayguinov YR, et a1. Involvement of intramuscular interstitial cells in nitrergic inhibition in the mouse gastric antrum. J Physiol, 2003; 546(Pt 3):751-763
52. Kito Y, Fukuta H, Yamamoto Y, et a1. Excitation of smooth muscles isolated from the guinea-pig gastric antrum in response to depolarization. J Physiol, 2002;543(Pt 1):155-167
53.刘勇,齐清会。MODS大鼠胃肠运动障碍机制和大承气冲剂的治疗作用。中国中西医结合外科杂志,2004; 10:430-432
54. Kohjitani A, Miyawaki T, Funahashi M, et al. Mexiletine inhibits nonadrenergic noncholinergic lower oesophageal sphincter relaxation in rabbits. Eur J Pharmacol, 2003; 465(1-2):145-151
55. Porter AJ, Wattchow DA, Brookes SJ, Costa M. Cholinergic and nitreric intemeurones in the myenteric plexus of the human colon. Gut, 2002; 51(1): 70-75
56.余跃.侯晓华.茹立强等.非溃疡性消化不良患者胃窦壁内NO能和VIP能神经与胃排空关系的研究.中华消化杂志,l 998; 18:291-294
57.龙庆林,王振华.氮能神经递质和胆碱能神经递质对大鼠胃电节律的影响.重庆医学,2003; 9:41-43
58. Berghe PV, Missiaen L, Bellon E. Free cytosolic Ca2+ recordings from myenteric neurons in multilayer intestinal preparations. Neurogastroenterol Mot. 2001; 13: 493-502
59. Salmhofer H, Neuhuber WT, Huber PR. Pivotal role of the interstitial cells of Cajal in the nitric oxide signaling pathway of rat small intestine. Cell Tissue Res. 2001; 305(3):331-340
60. Kimura H, Ito S, Ohta T. Vasoactive intestinal peptide released by acetylcholine in the dog ileum. J Auton Nerv Syst, 1994; 48(2):167-174
61. Tomita R, Fuiisaki S, Ikeda T, eta1. Role of nitric oxide in the colon of patients with slow-transit constipation. Dis Colon Rectum, 2002; 45(5):593-600.
62. Won KJ, Suzuki T, Hori M, et al. Motility disorder in experimentally obstructed intestine: relationship between muscularis inflammation and disruption of the ICC network. Neurogastroenterol Motil. 2006; 18:53-61
63. Rumessen JJ. Ultrastructure of interstitial cells of Cajal at the colonic submuscular border in patients with ulcerative colitis. Gastroenterology, 1996; 111:1447–1455
64. Suzuki T, Won KJ, Horiguchi K,et al. Muscularis inflammation and the loss of interstitial cells of Cajal inthe endothelin ETB receptor null rat. Am J Physiol, 2004; 287:G638–G646
65. Galeazzi F, Lovato P, Blennerhassett PA, etal. Neural change in Trichinella- infected mice is MHC II independent and involves M-CSF-derived macrophages.Am J Physiol, 2001; 281:G151-G158
66. Pellegrini MSF, Gay J, Vannucchi MG, et al. Alterations of neurokinin receptors and interstitial cells of Cajal during and after jejunal inˉammation induced by Nippostrongylus brasiliensis in the rat. Neurogastroenterol. Mot, 2002; 14:83-95
67. Porcher C, Baldo M, Henry M, et al. Deficiency of intersititial cells of Cajal in the small intestine of patients with Crohn’s disease. Am J Gastroenterol, 2002; 97(1):118-125
68. Seki K, Komuro T. Immunocytochemical demonstration of the gap junction proteins connexin 43 and connexin 45 in the musculature of the rat small intestine. Cell Tissue Res, 2001; 306:417–422
69. Simon AM. Gap junctions: more roles and new structural data. Trends Cell Biol, 1999; 9:169-170
70. Belzer V, Kobilo T, Rich A, Hanani M. Intercellular coupling among interstitial cells of Cajal in the guinea pig small intestine. Cell Tissue Res, 2002; 307:15–21
71. Belzer V, Nissan A, Freund HR, Hanani M. Coupling among interstitial cells of Cajal in the human ileum. Neurogastroenterol Motil, 2004; 16: 75–80
72. Kobilo T, Szurszewski JH, Farrugia G, Hanani M. Coupling and innervation patterns of interstitial cells of Cajal in the deep muscular plexus of the guinea-pig. Neurogastroenterol Motil, 2003; 15:635–641
73. Wang XY, Vannucchi MG, Nieuwmeyer F. Changes in interstitial cells of Cajal at the deep muscular plexus are associated with loss of distention-induced bust-type muscle activity in mice infected by trichinella spiralis. American Journal of Pathology.2005; 167:437-453
74.赵琪,崔乃强,周文洛,寒下药物对致病大肠杆菌DNA合成的抑制作用,中国中西医结合杂志,1995; 15(15):366-368
75.陈海龙,吴咸中,关风林等。中医通里攻下法对多器官功能不全综合征时肠道屏障功能保护作用的实验研究。中国中西医结合杂志,2000; 20:120-122
76.齐清会,王简,回建峰等,大承气冲剂对人体胃肠运动功能的影响。中国中西医结合杂志,2004; 24,1:17-20
77.邱奇,崔乃强,吴咸中。大承气冲剂对腹腔感染所致SIRS/MODS的治疗作用。中国中西医结合外科杂志。2004; 10:239-243。
78.崔克亮,曹书华,王今达。大承气汤对多器官功能障碍综合征防治作用的临床研究。中国中西医结合急救杂志,2003; 10:12-15
79.曹书华,王今达。大承气汤在多器官功能障碍综合征治疗过程中的免疫调节作用。中华创伤杂志,2004; 12:20-23
80.刘勇,齐清会。大承气冲剂治疗对多器官功能不全综合征胃肠Cajal间质细胞形态学影响。中国中西医结合外科杂志,2007; 13:53-58
1. Daniel EE. Communication between interstial cells of Cajal and gsstrointestinal mnscle. Neurogastroenterol Motil, 2004; 16 (1):118-122
2. Nemeth L,Puri P. Three-dimensinal morphology of C-Kit-positive cellular network and nitrergic innervation in the human gut. Arch Pathol Leb Med, 2001; 125:899
3. Ward SM,Beckett EAH,Wang XY. Interstitial cells of Cajal mediate cholinergic neurotransmission from enteric motor neurons. J.Neurosci, 2000; 20(4):1393- 1403
4. Wang XY, Paterson C, Huizinga JD. Cholinergic and nitrergic innervation of ICC-DMP and ICC-IM in the human small intestine. Neurogastroenterol motil, 2003; 15:531-543
5. Berghe PV, Missiaen L,Bellon E. Free cytosolic Ca2+ recordings from myenteric neurons in multilayer intestinal preparations. Neurogastroenterol Mot, 2001; 13: 493-502
6. Nakagawa T, Misawa H, Nakajima Y. Absence of peristalsis in the ileum of W/Wv mutant mice that are selectively deficient in myenteric interstitial cells of Cajal. J.Smooth Muscle Res, 2005; 41(3):141-151
7. Ward SM, Sanders km, Hirst GDS. Role of interstitial cells of Cajal in neural control of gastrointestinal smooth muscles. Neurogastroenterol Motil, 2004; 16;(suppl,1)112-117
8. Takeuchi T, Fujinami K, Okishio Y. Essential role of the interstitial cells of Cajal in Nitric Oxide-Mediated relaxation of longitudinal muscle of the mouse ileum. J Pharmacol Sci, 2004; 95:71-80
9. Beckett EAH, McGeough CA, Sandders KM. Pacing of interstitial cells of Cajal in the murine gastric antrum:neurally mediated and direct stimulation. J,Physiol, 2003; 553:545-559.
10. Wang XY, Vannucchi MG, Nieuwmeyer F. Changes in interstitial cells of Cajal at the deep muscular plexus are associated with loss of distention-induced bust-type muscle activity in mice infected by trichinella spiralis. American Journal of Pathology, 2005; 167:437-453
11. Seki K, Komuro T. Immunocytochemical demonstration of the gap junction proteins connexin 43 and connexin 45 in the musculature of the rat smallintestine. Cell Tissue Res, 2001; 306:417-422
12. Mitsui R, Komuro T. Direct and indirect innervation of smooth muscle cells of rat stomatch,with special reference to the interstitial cells of Cajal. Cell Tissue Res, 2002;309: 219-227
13. Belzer V, Nissan A, Freund HA, Hanani M. Coupling among interstitial cells of Cajal in the human ileum. Neurogastroenterol Motil, 2004; 16:75-80
14. Kobilo T, Szurszewski JH, Farrugia G, hanani M. Coupling and innervation patterns of interstitial cells of Cajal in the deep muscle plexus of the guinea-pig. Neurogastroenterol motil, 2003; 15:635-641
15. Belzer V, Kobilo T, Rich A, Hanani M. Intercellular coupling among interstitial cells of Cajal in the guinea pig small intestine. Cell Tissue Res, 2002; 307:15-21
16. Daniel EE,Thomas J,Ramnarain M,Bowes TJ,Jury J. Do gap junctions couple interstitial cells of Cajal pacing and neurotransmission to gastrointestinal smooth muscle? Neurogastroenterol Motil, 2001;13:297-307
17. Schultz T,Daniel V,Daniel EE. Does ICC pacing require functional gap junctions between ICC and smooth muscle in mouse intestine? Neurogastrenterol Motil, 2003; 15:129-138
18. Yamazawa T,Iino M. Simultaneous imaging of Ca2+ signals in interstitial cells of Cajal and longitudinal smooth muscle cells during rhythmic activity in mouse ileum. J Physiol, 2002; 538:823-835
19. Horiguchi K, Sanders KM, Ward SM. Enteric motor neurons from synaptic-like junctions with interstitial cells of Cajal in the canine gastric antrum. Cell Tissue Res, 2003; 311:299-313.
20. Thuneberg L, Peters S. Toward a concept of stretch-coupling in smooth muscle.I.Anatomy of interstitial segmentation and sleeve contractions. Anat Rec, 2001; 262:110-124
21. Ward SM,Sandders KM. Interstitial cells of Cajal :primary targets of enteric motor innervation. Anat Rec, 2001; 262:125-135
22. Epperson A,Hatton WJ,Callaghan B et al. Molecular components expressed in cultured and freshly isolated interstitial cells of Cajal. Am J Physiol, 2000; 279:C529-539
23. Salmhofer H, Neuhuber WL,Huber PR. Pivotal role of the interstitial cells of Cajal in the nitric oxide signaling pathway of rat small intestine. Cell Tissue Res., 2001; 305:331-340
24. Jun JY, Choi S, Yeum CH. Substeance P induced inward current and regulates pacemaker currents through tachykinin NK1 receptor in cultured interstitial cells of Cajal of murine small intestine. European Journal of Phamacology, 2004; 495:35-42
25. Harrington AM, Hutson JM, Southwell BR. Immunohistochemical localization of substance P NK1 receptor in guinea pig distal colon. Neurogastroenterol Motil, 2005; 17:727-737
26. Faussone-Pellegrini MS, Gay J, Vannucchi MG. Alterations of neurokinin receptors and interstitial cells of Cajal during and after jejunal inflammation induced by Nippostrongylus brasiliensis in the rat. Neurogastroenterol mot, 2004;14:83-95
27. Ward SM, Bayguinov J, Won KJ, Grundy D, Berthoud HR. Distribution of the vanilloid receptor (VR1) in the gastrointestinal tract. J Comp Neurol, 2003; 465: 121–35
28. Patterson LM,Zheng HY, Ward SM. Immunohistochemical identification of cholecystokinin A receptors on interstitial cells of Cajal,smooth muscle,and enteric neurons in rat pylorus. Cell Tissue Res, 2001;305:11-23
29. Vanderwinden JM, Liu H, Menu R, et al. The pathology of infantile hypertrophic pyloric stenosis after healing. J Pediatr Surg, 1996, 31:1530-1534
30.张亚萍,张宽学,高革,等.大鼠胃肠道Cajal间质细胞的超微结构研究.胃肠病学和肝病学杂志, 2002; 11(2): 112-114
31. Isozaki K, Hirota S, Miyagawa J, et al. Deficiency of c-Kit+ cells in patients with a myopathic form of chronic idiopathic intestinal pseudo-obstruction. Am J Gastroenterol, 1997; 92:332-334
32. Campbell F, Hewlett B, Ho J, et al. Interstitial cells of Cajal (ICC) are absent or deranged in intestinal pseudo-obstruction (Abstract). Lab Invest, 1998; 78:61A
33. Vanderwinden JM, Rumessen JJ. Interstitial cells of Cajal in human gut and gastrointestinal disease. Microsc Res Tech, 1999; 47(5):344-360
34. Huizinga JD, Berezin I, Sircar K, et al. Development of interstitial cells of Cajal in a full-term infant without an enteric nervous system. Gastroenterology, 2001;120(2):561-567
35. He CL, Soffer EE, Ferris CD, et al. Decreased interstitial cells of Cajal volume in patients with slow-transit constipation. Gastroenterology. 2000;118(1):14-21
36.童卫东,张胜本,张连阳,等.长期应用大黄对大鼠结肠肌电及Cajal间质细胞的影响.第三军医大学学报,2000; 22(4):351-353
37. Robertson K, Masson I, Hall S. Hirschsprung’s disease: genetic mutation in mice and men. Gut, 1997; 41:436-441
38. Rumessen JJ. Ultrastructure of interstitial cells of Cajal at the colonic subnuscular border in patients with ulcerative colitis. Gastroenterology, 1996; 111(6):1447-1455
2.岳茂兴。腹部外科疾病并发多器官功能障碍综合征代谢特点及分阶段营养支持治疗。中国危重病急救医学。2003;15:29-31
3.张趣,刘春峰。胃肠道与SIRS和MOD日本医学介绍,2005;26:281-283
4.王晓梅,董云,王一平。MODS与胃肠道关系。中华腹部疾病杂志,2003;3:379-340
5. Gregory M,Swank MD,Edwin A,ct a1.Role ofthe Gut in multiple organ failure:Bacterial translecation and penneablility changes.World J surg,1996;20:411-417
6. Tokyay R, Zeigler ST,Heggers JP,et a1.Efects of anesthesia,surgery fluid resuscitation and endotoxln administration on postbum bacterial translecation.J Trauma.1991;31:1376-1379
7. Hassoun HT,Kone BC,Mercer DW,et a1. Postinjury multiple organfailure:the role of the gut.Shock.2001;15(1):l-7
8.孟宪均.多器官功能障碍综合征研究展望.中华医学杂志,1998;78(6):407-408
9. Matejovie M,Rokyta R Jr,Kromecky A,et a1.Gastroitestinal tract dysfunction in critical illness.Gas Lek Cesk,2002;141(2):46-50
10. Ward SM, Sanders KM, Hirst GDS. Role of interstitial cells of Cajal in neural control of gastrointestinal smooth muscles. Neurogastroenterol Motil, 2004;16 (Suppl.1):112–117
11. Daniel EE. Communication between interstial cells of Cajal and gsstrointestinal mnscle. Neurogastroenterol Motil, 2004;16 (1):118-122
12. Hanani M, Freund HR. Interstitial cells of Cajal—their role in pacing and signal transmission in the digestive system. Acta Physiol Scand,2000;170(3):177-190
13. Wang XY, Paterson C, Huizinga JD. Cholinergic and nitrergic innervation of ICC-DMP and ICC-IM in the human small intestine. Neurogastroenterol motil. 2003;15:531-543
14. Huizinga JD, Ambrous K, Der-Silaphet TD: Co-operation between neural and myogenic mechanisms in the control of distension-induced peristalsis in the mouse small intestine. J Physiol (Lond) 1998;506:843–856
15. Wang XY, Sanders KM, Ward SM. Intimate relationship between interstitial cells of Cajal and enteric nerves in the guinea-pig small intestine. Cell TissueRes,1999;295:247-256
16. Laszlo Nemth, Peter Nemth, Edit Oszlacs, et al. C-kit positive cellular network on normal human bowel and in motility disorders. Acta Biol Szeged, 2001;45(1-4):57-64
17. Takayama I, Horiguchi K, Daigo Y, et al. The interstitial cells of Cajal and a gastroenteric pacemaker system. Arch Histol Cytol,2002;65:1-26
18. Epperson A,Hatton WJ,Callaghan B et al. Molecular components expressed in cultured and freshly isolated interstitial cells of Cajal. Am J Physiol 2000;279:C529-G539
19. Horiguchi K, Sanders KM, Ward SM. Enteric motor neurons form synaptic-like junctions with interstitial cells of Cajal in the canine gastric antrum. Cell Tissue Res,2003;311:299–313
20. Iion S, Ward SM, Sanders KM. Interstitial cells of Cajal are functiongal innervated by excitatory motor neurons in the murine intestine. J Physiol, 2004;556(2):521-530
21. Ward SM , Beckett EAH, Wang XY, et al. Interstitial cells of Cajal mediate cholinergic neurotransmission from enteric motor neurons. J Neurosci,2000;20(4):1393–1403
22. Wang XY, Sanders KM, Ward SM. Relationship between interstitial cells of Cajal and enteric motor neurons in the murine proximal colon. Cell Tissue Res, 2000;302:331–342
23. Takayama I, Daigao Y, Ward SM, et al. Differential gene expression in the small intestines of wild type and W/WV mice. Neurogastroenterol Motil, 2001;13:163-168
24. He CL, Burgart L, Wang L, et al. Decreased interstitial cells of Cajal volume in patients with slow-transit constipation. Gastroenterology, 2000;118:14-21
25. Ordog T, Ward SM, Sanders KM. Interstitial cells of Cajal generate electrical slow waves in the murine stomach, J Physiol, 1999;518,(Pt 1): 257-269
26. Dickens EJ, Edwards FR, Hirst GD. Selective knockout of intramuscular interstitial cells reveals their roles in the generation of slow waves oin mouse stomach. J Physiol, 2001;531,(Pt 3): 827-833
27. Tadayoshi Takeuchi,Kaori Fujinami,Yutaka Okishio. Essential role of the interstitial cells of Cajal in Nitric Oxide-Mediated relaxation of longitudinal muscle of the mouse ileum. J Pharmacol Sci. 2004;95:71-80
28. Toma H, Nakamura K, Emson PC, et al. Immunohistochenical distribution of C-kit-positive cells and nitric oxide synthase-positive nerves in the guinea-pig small intestine. J Auton Nerv Syst,1999; 75:93-99
29. Wang XY, Berezin I, Mikkelsen HB, et al. Pathology of interstitial cells of Cajal in relation to inflammation revealed by ultrastructure but not immunohistochemistry. Am J Pathol,2002; 160(4):1529-1540
30.刘勇,齐清会。多器官功能障碍综合征胃肠动力障碍与Cajal间质细胞关系及大承气冲剂治疗机理。2004,天津医科大学博士研究生学位论文。
31. Sanders KM, Ordog T, Koh SD. et al. Development and plasticity of interstitial cells of Cajal. Neurogastroenterol. Mot,1999; 11:311-338
32、Torihashi S, Ward SM, Nishikawa S-I, et al. C-kit-dependent development of interstitial cells and electrical activity in the murine gastrointestinal tract. Cell Tissue Res,1995; 280:97–111
32. Ward SM, Burns AJ, Torihashi S, et al. Mutation of the proto-oncogene c-kit blocks development of interstitial cells and electrical rhythmicity in murine intestine. J Physiol,1994; 480:91–97
33. Huizinga JD, Thuneberg L, Kluppel M, et al. W/kit gene required for interstitial cells of Cajal and for interstitial pacemaker activity. Nature,1995; 373:347-349
34. Pluja L, Alberti E, Fernandez E, Mikkelsen HB, et al. Evidence supporting presence of two pacemakers in rat colon. Am J Physiol Gastrointest Liver Physiol, 2001; 281(1):G255-G266
35. Nemeth L,Puri P. Three-dimensinal morphology of C-Kit-positive cellular network and nitrergic innervation in the human gut. Arch Pathol Leb Med. 2001;125:899-904
36.李丽,多器官功能障碍综合征炎症机制的研究进展现代诊断与治疗。2003; 14(3):164-166
37. Strieter RM, Kumkel SL, Bone RC. Role of tumor necrosis factor-αin disease states and inflammation. Crit Care Med, 1993; 2l (10Supp1): S447-463.
38. Fong Y, Lowrg SF. Tumor necrosis factor in the pathophysiology of infection and sepsis, Clin Immunol Immunopathol, 1990; 55(2):l57-170.
39.朱正华,曹祥龙,熊利泽。炎性免疫细胞凋亡在SIRS和MODS中的作用。中国危重病急救医学,1999; l1:507-509
40.黄重敏,陆富刚,MODS免疫发病机制的研究进展,中国急救医学,2002,22:739-740
41. Ward SM, Ordog T, Koh SD, et al. Pacemaking in interstitial cells of Cajal depends upon calcium handing by endoplasmic reticulum and mitochondria, J Physiol (Lond), 2000; 525:355-361
42. Liu X, Kim CN, Yang J, et al. Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell, 1996; 86:147-157
43. Lu G, Qian X, Berezin I, et al. Imflammation modulates in vitro colonic myoelectric and contractive activity and interstitial cells of Cajal. Am J Physiol,1997; 273(6 Pt 1): G1233-G1245
44. Huizinga JD. Neural injury, repair, and adaptation in the GI tract. IV. Pathophysiology of GI motility relaed to interstitial cells of Cajal. Am J Physiol,1998; 275(Pt 1):G381-G386
45. Ekblad E, Sjuve R, Arner A, Sundler F. Enteric neuroal plasticity and a reduced number of interstitial cells of Cajal in hypertrophic rat ileum, Gut, 1998: Jun;42(6):836-844
46. Altdorfer K, Bagameri G, Donath T, et al. Nitric oxide synthase immunoreactivity of interstitial cells of Cajal in experimental colitis. Inflamm Res,2002; 51:569-571
47. Der T, Bercik P, Donnelly G, et al. Interstitial cells of Cajal and inflammation- induced motor dysfunction in the mouse small intestine. Gastroenterology, 2000; 119(6):1590-1599
48. Nemeth L, Fourcade L, Puri P. Marked morphological differences in the myenteric plexus between the mesenteric and antimesenteric sides of small bowel in premature infants. J Pediatr Surg, 2000; 35(5): 748-752.
49. Kobayashi H, Li Z, Yamataka A, et a1. Acetylcholinesterase distribution and refractory constipation-a new criterion for diagnosis and management. Pediatr surg Int, 2002; 18(5-6): 349-353.
50. Dinah TG, Scott LV, Brady D, et a1. Altered hypothalamie cholinergie responses in patients with nonulcer dyspepsia: a study of pyridostigmine- stimulated growth hormone release. Am J Gastroenterol, 2002; 97 (8):1937-1940.
51. Suzuki H, Ward SM, Bayguinov YR, et a1. Involvement of intramuscular interstitial cells in nitrergic inhibition in the mouse gastric antrum. J Physiol, 2003; 546(Pt 3):751-763
52. Kito Y, Fukuta H, Yamamoto Y, et a1. Excitation of smooth muscles isolated from the guinea-pig gastric antrum in response to depolarization. J Physiol, 2002;543(Pt 1):155-167
53.刘勇,齐清会。MODS大鼠胃肠运动障碍机制和大承气冲剂的治疗作用。中国中西医结合外科杂志,2004; 10:430-432
54. Kohjitani A, Miyawaki T, Funahashi M, et al. Mexiletine inhibits nonadrenergic noncholinergic lower oesophageal sphincter relaxation in rabbits. Eur J Pharmacol, 2003; 465(1-2):145-151
55. Porter AJ, Wattchow DA, Brookes SJ, Costa M. Cholinergic and nitreric intemeurones in the myenteric plexus of the human colon. Gut, 2002; 51(1): 70-75
56.余跃.侯晓华.茹立强等.非溃疡性消化不良患者胃窦壁内NO能和VIP能神经与胃排空关系的研究.中华消化杂志,l 998; 18:291-294
57.龙庆林,王振华.氮能神经递质和胆碱能神经递质对大鼠胃电节律的影响.重庆医学,2003; 9:41-43
58. Berghe PV, Missiaen L, Bellon E. Free cytosolic Ca2+ recordings from myenteric neurons in multilayer intestinal preparations. Neurogastroenterol Mot. 2001; 13: 493-502
59. Salmhofer H, Neuhuber WT, Huber PR. Pivotal role of the interstitial cells of Cajal in the nitric oxide signaling pathway of rat small intestine. Cell Tissue Res. 2001; 305(3):331-340
60. Kimura H, Ito S, Ohta T. Vasoactive intestinal peptide released by acetylcholine in the dog ileum. J Auton Nerv Syst, 1994; 48(2):167-174
61. Tomita R, Fuiisaki S, Ikeda T, eta1. Role of nitric oxide in the colon of patients with slow-transit constipation. Dis Colon Rectum, 2002; 45(5):593-600.
62. Won KJ, Suzuki T, Hori M, et al. Motility disorder in experimentally obstructed intestine: relationship between muscularis inflammation and disruption of the ICC network. Neurogastroenterol Motil. 2006; 18:53-61
63. Rumessen JJ. Ultrastructure of interstitial cells of Cajal at the colonic submuscular border in patients with ulcerative colitis. Gastroenterology, 1996; 111:1447–1455
64. Suzuki T, Won KJ, Horiguchi K,et al. Muscularis inflammation and the loss of interstitial cells of Cajal inthe endothelin ETB receptor null rat. Am J Physiol, 2004; 287:G638–G646
65. Galeazzi F, Lovato P, Blennerhassett PA, etal. Neural change in Trichinella- infected mice is MHC II independent and involves M-CSF-derived macrophages.Am J Physiol, 2001; 281:G151-G158
66. Pellegrini MSF, Gay J, Vannucchi MG, et al. Alterations of neurokinin receptors and interstitial cells of Cajal during and after jejunal inˉammation induced by Nippostrongylus brasiliensis in the rat. Neurogastroenterol. Mot, 2002; 14:83-95
67. Porcher C, Baldo M, Henry M, et al. Deficiency of intersititial cells of Cajal in the small intestine of patients with Crohn’s disease. Am J Gastroenterol, 2002; 97(1):118-125
68. Seki K, Komuro T. Immunocytochemical demonstration of the gap junction proteins connexin 43 and connexin 45 in the musculature of the rat small intestine. Cell Tissue Res, 2001; 306:417–422
69. Simon AM. Gap junctions: more roles and new structural data. Trends Cell Biol, 1999; 9:169-170
70. Belzer V, Kobilo T, Rich A, Hanani M. Intercellular coupling among interstitial cells of Cajal in the guinea pig small intestine. Cell Tissue Res, 2002; 307:15–21
71. Belzer V, Nissan A, Freund HR, Hanani M. Coupling among interstitial cells of Cajal in the human ileum. Neurogastroenterol Motil, 2004; 16: 75–80
72. Kobilo T, Szurszewski JH, Farrugia G, Hanani M. Coupling and innervation patterns of interstitial cells of Cajal in the deep muscular plexus of the guinea-pig. Neurogastroenterol Motil, 2003; 15:635–641
73. Wang XY, Vannucchi MG, Nieuwmeyer F. Changes in interstitial cells of Cajal at the deep muscular plexus are associated with loss of distention-induced bust-type muscle activity in mice infected by trichinella spiralis. American Journal of Pathology.2005; 167:437-453
74.赵琪,崔乃强,周文洛,寒下药物对致病大肠杆菌DNA合成的抑制作用,中国中西医结合杂志,1995; 15(15):366-368
75.陈海龙,吴咸中,关风林等。中医通里攻下法对多器官功能不全综合征时肠道屏障功能保护作用的实验研究。中国中西医结合杂志,2000; 20:120-122
76.齐清会,王简,回建峰等,大承气冲剂对人体胃肠运动功能的影响。中国中西医结合杂志,2004; 24,1:17-20
77.邱奇,崔乃强,吴咸中。大承气冲剂对腹腔感染所致SIRS/MODS的治疗作用。中国中西医结合外科杂志。2004; 10:239-243。
78.崔克亮,曹书华,王今达。大承气汤对多器官功能障碍综合征防治作用的临床研究。中国中西医结合急救杂志,2003; 10:12-15
79.曹书华,王今达。大承气汤在多器官功能障碍综合征治疗过程中的免疫调节作用。中华创伤杂志,2004; 12:20-23
80.刘勇,齐清会。大承气冲剂治疗对多器官功能不全综合征胃肠Cajal间质细胞形态学影响。中国中西医结合外科杂志,2007; 13:53-58
1. Daniel EE. Communication between interstial cells of Cajal and gsstrointestinal mnscle. Neurogastroenterol Motil, 2004; 16 (1):118-122
2. Nemeth L,Puri P. Three-dimensinal morphology of C-Kit-positive cellular network and nitrergic innervation in the human gut. Arch Pathol Leb Med, 2001; 125:899
3. Ward SM,Beckett EAH,Wang XY. Interstitial cells of Cajal mediate cholinergic neurotransmission from enteric motor neurons. J.Neurosci, 2000; 20(4):1393- 1403
4. Wang XY, Paterson C, Huizinga JD. Cholinergic and nitrergic innervation of ICC-DMP and ICC-IM in the human small intestine. Neurogastroenterol motil, 2003; 15:531-543
5. Berghe PV, Missiaen L,Bellon E. Free cytosolic Ca2+ recordings from myenteric neurons in multilayer intestinal preparations. Neurogastroenterol Mot, 2001; 13: 493-502
6. Nakagawa T, Misawa H, Nakajima Y. Absence of peristalsis in the ileum of W/Wv mutant mice that are selectively deficient in myenteric interstitial cells of Cajal. J.Smooth Muscle Res, 2005; 41(3):141-151
7. Ward SM, Sanders km, Hirst GDS. Role of interstitial cells of Cajal in neural control of gastrointestinal smooth muscles. Neurogastroenterol Motil, 2004; 16;(suppl,1)112-117
8. Takeuchi T, Fujinami K, Okishio Y. Essential role of the interstitial cells of Cajal in Nitric Oxide-Mediated relaxation of longitudinal muscle of the mouse ileum. J Pharmacol Sci, 2004; 95:71-80
9. Beckett EAH, McGeough CA, Sandders KM. Pacing of interstitial cells of Cajal in the murine gastric antrum:neurally mediated and direct stimulation. J,Physiol, 2003; 553:545-559.
10. Wang XY, Vannucchi MG, Nieuwmeyer F. Changes in interstitial cells of Cajal at the deep muscular plexus are associated with loss of distention-induced bust-type muscle activity in mice infected by trichinella spiralis. American Journal of Pathology, 2005; 167:437-453
11. Seki K, Komuro T. Immunocytochemical demonstration of the gap junction proteins connexin 43 and connexin 45 in the musculature of the rat smallintestine. Cell Tissue Res, 2001; 306:417-422
12. Mitsui R, Komuro T. Direct and indirect innervation of smooth muscle cells of rat stomatch,with special reference to the interstitial cells of Cajal. Cell Tissue Res, 2002;309: 219-227
13. Belzer V, Nissan A, Freund HA, Hanani M. Coupling among interstitial cells of Cajal in the human ileum. Neurogastroenterol Motil, 2004; 16:75-80
14. Kobilo T, Szurszewski JH, Farrugia G, hanani M. Coupling and innervation patterns of interstitial cells of Cajal in the deep muscle plexus of the guinea-pig. Neurogastroenterol motil, 2003; 15:635-641
15. Belzer V, Kobilo T, Rich A, Hanani M. Intercellular coupling among interstitial cells of Cajal in the guinea pig small intestine. Cell Tissue Res, 2002; 307:15-21
16. Daniel EE,Thomas J,Ramnarain M,Bowes TJ,Jury J. Do gap junctions couple interstitial cells of Cajal pacing and neurotransmission to gastrointestinal smooth muscle? Neurogastroenterol Motil, 2001;13:297-307
17. Schultz T,Daniel V,Daniel EE. Does ICC pacing require functional gap junctions between ICC and smooth muscle in mouse intestine? Neurogastrenterol Motil, 2003; 15:129-138
18. Yamazawa T,Iino M. Simultaneous imaging of Ca2+ signals in interstitial cells of Cajal and longitudinal smooth muscle cells during rhythmic activity in mouse ileum. J Physiol, 2002; 538:823-835
19. Horiguchi K, Sanders KM, Ward SM. Enteric motor neurons from synaptic-like junctions with interstitial cells of Cajal in the canine gastric antrum. Cell Tissue Res, 2003; 311:299-313.
20. Thuneberg L, Peters S. Toward a concept of stretch-coupling in smooth muscle.I.Anatomy of interstitial segmentation and sleeve contractions. Anat Rec, 2001; 262:110-124
21. Ward SM,Sandders KM. Interstitial cells of Cajal :primary targets of enteric motor innervation. Anat Rec, 2001; 262:125-135
22. Epperson A,Hatton WJ,Callaghan B et al. Molecular components expressed in cultured and freshly isolated interstitial cells of Cajal. Am J Physiol, 2000; 279:C529-539
23. Salmhofer H, Neuhuber WL,Huber PR. Pivotal role of the interstitial cells of Cajal in the nitric oxide signaling pathway of rat small intestine. Cell Tissue Res., 2001; 305:331-340
24. Jun JY, Choi S, Yeum CH. Substeance P induced inward current and regulates pacemaker currents through tachykinin NK1 receptor in cultured interstitial cells of Cajal of murine small intestine. European Journal of Phamacology, 2004; 495:35-42
25. Harrington AM, Hutson JM, Southwell BR. Immunohistochemical localization of substance P NK1 receptor in guinea pig distal colon. Neurogastroenterol Motil, 2005; 17:727-737
26. Faussone-Pellegrini MS, Gay J, Vannucchi MG. Alterations of neurokinin receptors and interstitial cells of Cajal during and after jejunal inflammation induced by Nippostrongylus brasiliensis in the rat. Neurogastroenterol mot, 2004;14:83-95
27. Ward SM, Bayguinov J, Won KJ, Grundy D, Berthoud HR. Distribution of the vanilloid receptor (VR1) in the gastrointestinal tract. J Comp Neurol, 2003; 465: 121–35
28. Patterson LM,Zheng HY, Ward SM. Immunohistochemical identification of cholecystokinin A receptors on interstitial cells of Cajal,smooth muscle,and enteric neurons in rat pylorus. Cell Tissue Res, 2001;305:11-23
29. Vanderwinden JM, Liu H, Menu R, et al. The pathology of infantile hypertrophic pyloric stenosis after healing. J Pediatr Surg, 1996, 31:1530-1534
30.张亚萍,张宽学,高革,等.大鼠胃肠道Cajal间质细胞的超微结构研究.胃肠病学和肝病学杂志, 2002; 11(2): 112-114
31. Isozaki K, Hirota S, Miyagawa J, et al. Deficiency of c-Kit+ cells in patients with a myopathic form of chronic idiopathic intestinal pseudo-obstruction. Am J Gastroenterol, 1997; 92:332-334
32. Campbell F, Hewlett B, Ho J, et al. Interstitial cells of Cajal (ICC) are absent or deranged in intestinal pseudo-obstruction (Abstract). Lab Invest, 1998; 78:61A
33. Vanderwinden JM, Rumessen JJ. Interstitial cells of Cajal in human gut and gastrointestinal disease. Microsc Res Tech, 1999; 47(5):344-360
34. Huizinga JD, Berezin I, Sircar K, et al. Development of interstitial cells of Cajal in a full-term infant without an enteric nervous system. Gastroenterology, 2001;120(2):561-567
35. He CL, Soffer EE, Ferris CD, et al. Decreased interstitial cells of Cajal volume in patients with slow-transit constipation. Gastroenterology. 2000;118(1):14-21
36.童卫东,张胜本,张连阳,等.长期应用大黄对大鼠结肠肌电及Cajal间质细胞的影响.第三军医大学学报,2000; 22(4):351-353
37. Robertson K, Masson I, Hall S. Hirschsprung’s disease: genetic mutation in mice and men. Gut, 1997; 41:436-441
38. Rumessen JJ. Ultrastructure of interstitial cells of Cajal at the colonic subnuscular border in patients with ulcerative colitis. Gastroenterology, 1996; 111(6):1447-1455