乌司他丁对重症肺炎大鼠CD4^+CD25^+调节性T细胞及相关细胞因子的调控机制分析  

Analysis on regulatory mechanism of ulinastatin on CD4^+,CD25^+,regulatory T cells and related cytokines in severe pneumonia rats.

作　　者：王亮 范菱 黄德亮 WANG Liang;FAN Ling;HUANG De-liang(Department of Pediatrics,Jingzhou Second People's Hospital,Jingzhou Hubei 434000,China.)

机构地区：[1]荆州市第二人民医院儿二科,湖北荆州434000

出　　处：《临床和实验医学杂志》2020年第12期1263-1266,共4页Journal of Clinical and Experimental Medicine

基　　金：湖北省科技厅自然科学基金(编号:2010CDB09103)。

摘　　要：目的探究乌司他丁对重症肺炎大鼠CD4^+CD25^+调节性T细胞及相关细胞因子的调控机制。方法选取60只雄性SD大鼠,将其中的45只采用肺炎克雷伯杆菌标准菌株感染SD大鼠,建立大鼠重症肺炎模型,并分为模型组、低剂量乌司他丁组(腹腔注射乌司他丁5×10^4 U/kg)和高剂量乌司他丁组(腹腔注射乌司他丁10×10^4 U/kg),另外15只作为空白对照组,空白对照组和模型组给予注射等量的生理盐水。使用流式细胞仪检测各组大鼠7 d、9 d、11 d外周血及肺泡灌洗液(BALF)中CD4^+、CD25^+、Treg细胞表达;检测各组大鼠外周血及BALF中白细胞(WBC)、中性粒细胞(PMN)水平;使用酶联免疫吸附试验检测各组大鼠外周血白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)、白细胞介素-4(IL-4)及白细胞介素-10(IL-10)水平。结果与空白对照组比较,模型组大鼠各时间段外周血及BALF中Treg/CD4^+T细胞比值、WBC、PMN,血清中IL-6、TNF-α水平显著升高(P<0.05),血清中IL-4水平显著降低(P<0.05);与模型组比较,使用乌司他丁处理各组大鼠各时间段外周血及BALF中Treg/CD4^+T细胞比值、WBC、PMN,血清中IL-6、TNF-α水平显著降低,且呈浓度依赖性(P<0.05),血清中IL-4水平显著升高,且呈浓度依赖性(P<0.05)。结论乌司他丁可以通过调节大鼠免疫功能及炎症因子降低重症肺炎大鼠并且严重程度,且在一定剂量范围内呈剂量依赖性。Objective To investigate the regulatory mechanism of ulinastatin(UTI)on CD4^+,CD25^+,regulatory T cells and related cytokines in severe pneumonia rats.Methods 60 male SD rats were enrolled.45 of them were infected with SD rats by standard strain of Klebsiella pneumoniae.The model of severe pneumonia rat was established.Tehy were divided into model group,low-dose UTI group(5×10^4U/kg)and high-dose UTI group(10×10^4U/kg).The other 15 cases were enrolled as blank control group(Control).Flow cytometry was performed to detect expression of CD4^+,CD25^+and Treg cells in peripheral blood and brocho-alveolar larage fluid(BALF)in each group on 7th,9th and 11th d.The levels of white blood cells(WBC)and neutrophil(PMN)in peripheral blood and BALF of each group were detected.The levels of interleukin-6(IL-6),tumor necrosis factorα(TNF-α),interleukin-4(IL-4)and interleukin-10(IL-10)in peripheral blood of each group were detected by Elisa.Results Compared with blank control group,Treg/CD4^+T cells ratio in peripheral blood and BALF,WBC,PMN,levels of serum IL-6 and TNF-αin model group were significantly increased all the time(P<0.05),while serum IL-4 level was significantly decreased(P<0.05).Compared with model group,Treg/CD4^+T cells ratio in peripheral blood and BALF,WBC,PMN,levels of serum IL-6 and TNF-αin all groups treated with UTI were significantly decreased all the time,showing concentration-dependence(P<0.05),while serum IL-4 level was significantly increased,showing concentration-dependence(P<0.05).Conclusion UTI can reduce severity of severe pneumonia rats by regulating immune function and inflammatory factors in rats,showing concentration-dependence in a certain dose range.

关 键 词：大鼠 重症肺炎 乌司他丁 T细胞 细胞因子 

分 类 号：R563.1[医药卫生—呼吸系统]