Cajal细胞在脓毒症所致胃肠动力障碍中的形态改变及厚朴酚干预的实验研究

doi:10.3969/j.issn.1006-7795.2013.02.001

首都医科大学学报 ›› 2013, Vol. 34 ›› Issue (2): 163-170.doi: 10.3969/j.issn.1006-7795.2013.02.001

Cajal细胞在脓毒症所致胃肠动力障碍中的形态改变及厚朴酚干预的实验研究

苗彬¹, 张淑文¹, 王红¹, 杨铁城², 周德山³, 王宝恩¹

1. 首都医科大学附属北京友谊医院感染内科, 北京 100050;
2. 首都医科大学附属北京天坛医院急诊科, 北京 100053;
3. 首都医科大学基础医学院解剖与组织胚胎学教研室, 北京 100069

收稿日期:2013-01-16 出版日期:2013-04-21 发布日期:2013-04-17
通讯作者: 张淑文 E-mail:zhangsw401106@sina.com
基金资助:
国家自然科学基金资助(81173411)。

Magnolol pretreatment prevents sepsis-induced intestinal dysmotility by maintaining functional interstitial cells of Cajal

MIAO Bin¹, ZHANG Shuwen¹, WANG Hong¹, YANG Tiecheng², ZHOU Deshan³, WANG Baoen¹

1. Department of Infection, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China;
2. Department of Emergency, Beijing Tiantan Hospital, Capital Medical University, Beijing 100053, China;
3. Department of Histology and Embryology, School of Basic Medical Science, Capital Medical University, Beijing 100069, China

Received:2013-01-16 Online:2013-04-21 Published:2013-04-17
Supported by:
This study was supported by the National Natural Science Foundation of China(81173411).

摘要/Abstract

摘要：

目的研究Cajal细胞在脓毒症所致胃肠运动障碍中的形态变化,以及厚朴酚和莫沙必利干预对其影响。方法采用尾静脉注射内毒素的方法制备脓毒症小鼠模型。动物采用数字表法随机分为4组,分别为对照组、脓毒症模型组、模型厚朴酚干预组和模型莫沙必利干预组。造模后12 h分别测定各组小肠传输速率、小肠平滑肌肌条自主收缩频率以及波幅,进行小肠动力学研究。制备小肠平滑肌铺片,以免疫荧光组织化学染色法观察各组间小肠Cajal细胞形态变化并定量计算细胞数量和细胞突触长度。提取小肠肌条组织测定超氧化物歧化酶活力和丙二醛含量以及一氧化氮含量,评价脓毒症时小肠氧化应激状态。结果造模12 h后,脓毒症模型组小肠传输速率较对照组明显减慢(P<0.05),厚朴酚和莫沙必利干预可以明显增加小肠传输速率(P<0.05)。造模12 h后,脓毒症模型组小肠肌条自主收缩频率和波长较对照组明显减慢(P<0.05),厚朴酚和莫沙必利干预可以明显增加小肠肌条收缩频率和波长(P<0.05)。小肠肌条铺片免疫荧光组织化学染色显示,同对照组相比,脓毒症模型组的Cajal细胞数量明显减少,从正常的每mm²有235个降低到113左右,残存细胞的突起变粗,长度也缩短,分支减少,不能形成完整的细胞网络。在厚朴酚干预组中,平均每mm²有201个作用小肠Cajal细胞,较脓毒症模型组上升;平均每个细胞的突起长度为687 μm并形成复杂的细胞网络,平均每个细胞的突触长度和总细胞的突触长度较脓毒症模型组增加。在莫沙必利干预组中,也可以见到小肠Cajal细胞数量较脓毒症模型组上升,平均每个细胞的突触长度和总细胞的突触长度增加。与对照组相比,脓毒症模型组小肠组织超氧化物歧化酶活力明显降低(P<0.05 ),丙二醛浓度显著增高(P<0.05 ),小肠组织一氧化氮浓度显著增高(P<0.05),提示脓毒症时小肠处于过度氧化应激状态。厚朴酚干预可以增加超氧化物歧化酶活力(P<0.05 ),丙二醛水平降低(P<0.05 ),明显降低小肠组织一氧化氮水平(P<0.05),提示厚朴酚可以纠正脓毒症时的过度氧化应激。但莫沙必利干预和脓毒症模型组相比,超氧化物歧化酶活力、丙二醛浓度以及一氧化氮浓度差异无统计学意义。结论脓毒症时可发生严重的胃肠运动障碍,Cajal细胞形态学发生明显变化。肠道氧化应激是胃肠运动障碍重要发生机制。厚朴酚可以改善脓毒症所致胃肠运动障碍。拮抗氧化应激和调控Cajal细胞可能是其产生这一作用的机制。

关键词: Cajal细胞, 厚朴酚, 一氧化氮, 氧化应激

Abstract:

Objective To investigate the mechanism by which magnolol treatment prevents sepsis-induced dysmotility in lipopolysaccharide(LPS)-treated mice. Methods Sepsis was induced by intravenous(tail vein) injection of LPS. Animals were divided into four groups: the magnolol-treated septic group, the mosapride-treated septic group,the placebo-treated septic group, and the control group. Intestinal transit and circular smooth muscle contraction were measured 12 h after LPS injection, and immunocytochemisty was performed to study the morphology of ICCs. NO content, superoxide dismutase(SOD) activity, and malondialdehyde(MDA) concentration were detected using commercial kits. Results Intestinal transit and muscular contractility were significantly lower in the LPS-treated group than in the control group. Immunocytochemical experiments showed that the total number of ICCs, and the total and average lengths of the ICC processes were significantly decreased in the LPS-treated group compared with those in the control group. In LPS-treated animals, magnolol pretreatment significantly accelerated intestinal transit, increased circular muscle contraction, and prevented ICC morphological changes. Magnolol pretreatment prevented the sepsis-induced increase in NO concentration, and MDA concentration, and decrease in SOD activity in LPS-treated animals. Conclusion Magnolol treatment prevented sepsis-induced intestinal dysmotility by regulating oxidative stress to maintain functional ICCs.

Key words: Cajal cells, magnolol, nitric oxide, oxidative stress

中图分类号:

R969.4

苗彬, 张淑文, 王红, 杨铁城, 周德山, 王宝恩. Cajal细胞在脓毒症所致胃肠动力障碍中的形态改变及厚朴酚干预的实验研究[J]. 首都医科大学学报, 2013, 34(2): 163-170.

MIAO Bin, ZHANG Shuwen, WANG Hong, YANG Tiecheng, ZHOU Deshan, WANG Baoen. Magnolol pretreatment prevents sepsis-induced intestinal dysmotility by maintaining functional interstitial cells of Cajal[J]. Journal of Capital Medical University, 2013, 34(2): 163-170.

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Cajal细胞在脓毒症所致胃肠动力障碍中的形态改变及厚朴酚干预的实验研究

Magnolol pretreatment prevents sepsis-induced intestinal dysmotility by maintaining functional interstitial cells of Cajal

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