Zhang Yijing, Li Ming, Meng Mei, Qin Chengyong
Department of Gastroenterology, Shandong Provincial Hospital, Shandong University, Jinan, People's Republic of China.
J Trauma. 2009 May;66(5):1355-64. doi: 10.1097/TA.0b013e31817d0568.
Physical and immunologic barriers of the small intestine play an important role in development and treatment of sepsis, so a rat model of sepsis was used to investigate the effect of ethyl pyruvate (EP) on the barriers.
Male Wistar rats were divided into sham operated, cecal ligation and puncture, and EP groups. Survival and bacterial translocation were measured in response to EP administration. Physical barrier (including mitochondria of enterocyte, tight junction, microvilli, and the grade of small intestinal mucosa damage) and immunologic barrier (including distribution of T-cell subgroups in small intestinal villi, proportion of T-cell subgroups in mesenteric lymph nodes and spleens, proliferation and cytokines release of splenocytes) were determined by electron and light microscopy, immunohistochemistry, flow cytometry, and enzyme-linked immunosorbent assay, respectively.
Sepsis induced morphologic alteration and immunosuppression in the small intestine. EP administration can prevent these changes, especially immunologic change. Distribution of CD4+ T cells in villi, proportions of CD4+ T cells in mesenteric lymph nodes and spleens, and proliferative capacity of splenocytes were increased in rats treated with EP. Interferon-gamma and Interleukin-4 release were also modulated. Moreover, EP improved survival from 37.1% to 57.1% and reduced bacterial translocation.
EP administration ameliorated physical and immunologic barriers dysfunction of small intestine in a rat model of sepsis. EP may be used to treat sepsis as an immunologic modulator.
小肠的物理和免疫屏障在脓毒症的发生发展及治疗中起重要作用,因此采用脓毒症大鼠模型来研究丙酮酸乙酯(EP)对这些屏障的影响。
将雄性Wistar大鼠分为假手术组、盲肠结扎穿孔组和EP组。测定给予EP后大鼠的存活率和细菌移位情况。分别通过电子显微镜和光学显微镜、免疫组织化学、流式细胞术及酶联免疫吸附测定法来确定物理屏障(包括肠上皮细胞线粒体、紧密连接、微绒毛以及小肠黏膜损伤程度)和免疫屏障(包括小肠绒毛中T细胞亚群的分布、肠系膜淋巴结和脾脏中T细胞亚群的比例、脾细胞的增殖及细胞因子释放)。
脓毒症可导致小肠形态改变和免疫抑制。给予EP可预防这些变化,尤其是免疫方面的变化。给予EP的大鼠绒毛中CD4⁺T细胞的分布、肠系膜淋巴结和脾脏中CD4⁺T细胞的比例以及脾细胞的增殖能力均增加。干扰素-γ和白细胞介素-4的释放也受到调节。此外,EP使存活率从37.1%提高到57.1%,并减少了细菌移位。
在脓毒症大鼠模型中,给予EP可改善小肠的物理和免疫屏障功能障碍。EP可作为一种免疫调节剂用于治疗脓毒症。