TGF-β1在脓毒症炎症反应中的变化及作用：体内及体外研究  

The effect of TGF-β1 on inflammatory factors in an experimental sepsis model and THP-1 cells

作　　者：张彧[1] 邢静[1] 李荟苹[1] 

机构地区：[1]大连医科大学附属第一医院急诊科,辽宁大连116011

出　　处：《中国急救医学》2016年第4期307-311,I0001,共6页Chinese Journal of Critical Care Medicine

基　　金：辽宁省教育厅科学研究一般项目

摘　　要：目的动态观察脓毒症大鼠外周血转化生长因子-β1（TGF—β1）在体内外炎症反应中的表达变化，了解其在炎症反应中的表达特点，同时通过体外实验研究，探讨TGF—β1调节脓毒症炎症反应的作用及机制。方法体内实验：通过盲肠结扎穿孔法（cecal ligation puncture，CLP）制备大鼠脓毒症模型，ELASA法检测不同时间点大鼠外周血TGF—β1、TNF-α及IL-10水平的变化，比较三者之间的关系，观察各脏器病理变化及大鼠死亡率。体外实验：采用TGF-β1siRNA技术，检测THP-1细胞培养液中TNF-α、IL-10表达水平，探讨体外TGF—β1调节炎症反应的作用。结果脓毒症大鼠外周血TGF—β1、TNF-α及IL-10表达水平在CLP后6～48h均明显升高，与对照组比较差异均有统计学意义（P〈0．05），其中TGF—β1在CLP后24h升高最明显。体外对TGF-β1RNAi干扰后，THP-1细胞分泌TNF—α明显增加（P〈0．05），而对IL-10无明显影响。结论TGF-β1在脓毒症的病理过程中表达增加，参与脓毒症炎症反应，可抑制TNF-α的生成，发挥抗炎症反应作用，但是对抗炎因子IL-10无明显影响。Objective This study aimed to investigate the dynamic change of TGF-β1 in serum of a cecal ligation and puncture （CLP） sepsis model in rats, with its effects on inflammatory factors, and discuss the mechanism of TGF-β1 in THP-1 cells. Methods A total of 152 Sprague-Dawley rats were used in vivo experiment. The rats were randomly divided into two groups, including control group （n = 32, four sub-groups, each sub-group 8 rats） and model group （n = 120, four sub-groups, each sub-group 30 rats）. Rats in control groups were sacrificed after anesthesia. Rats in model groups were sacrificed on different time points （6 h, 12 h, 24 h, 48 h） after CLP. The serum was collected to investigate the level of TGF-β1, TNF-α and IL-10 at the same time. Rat＇s mortality and pathological changes were also investigated. By TGF-β1 siRNA technology, the level of TNF-α and 1L-10 were tested in the THP-1 cell culture medium. Results In model groups, the levels of TGF-β1, TNF-α and IL-10 were significantly increased at all the time points after CLP （P 〈 0.05）. The level of TGF-β1 in serum reached the peak at 24 h after CLP. The mortality of rats increased as time gone by. Histopathological resuits in model groups were significantly different from those in the control group. Compared with NC group, cell secretion of TNF-α in THP-1 cells after TGF-β1 RNAi significantly increased （P 〈 0.05）, while the secretion of IL- 10 did not increased （P 〉 0.05）. Conclusion The findings obtained from the experimental sepsis model suggest that TGF-β 1 is involved in inflammatory process in sepsis. The findings obtained from the vitro experiment indicates that TNF-α should be promoted by TGF-β1 RNAi in THP-I cell, while IL-10 should not be ＂affected.

关 键 词：脓毒症 转化生长因子-β1(TGF-β1) TGF-Β1 RNAI 炎症反应 

分 类 号：R575.2[医药卫生—消化系统]