摘要
目的研究白细胞介素-12(IL-12)单克隆抗体对克罗恩病模型小鼠辅助性T细胞1/辅助性T细胞2(Th1/Th2)免疫平衡的调节作用。方法选择BALB/c健康小鼠30只,将30只小鼠分为正常对照组(10只)和实验小鼠(20只),实验组小鼠做克罗恩病模型,建模成功后将实验组小鼠分为克罗恩病组和IL-12单克隆抗体组各10只,IL-12单抗组小鼠腹腔注射IL-12单抗(25 mg/kg),正常对照组和克罗恩病组小鼠腹腔注射0.2 ml的生理盐水。处理4周后,对三组小鼠疾病活动程度、结肠重量、结肠长度进行评价,使用酶联免疫吸附试验法检测三组小鼠结肠组织中Th1型细胞因子干扰素-γ(IFN-γ)、肿瘤坏死因子-α(TNF-α)、IL-1β、IL-8和Th2型细胞因子IL-4、IL-10及IL-12、IL-23表达水平。结果克罗恩病组小鼠疾病活动程度评分、结肠组织中Th1型细胞因子IFN-γ、TNF-α、IL-1β、IL-8、IL-12、IL-23分别为(4.12±0.23)分、(563.49±21.36)ng/ml、(120.69±6.69)ng/L、(43.73±3.58)ng/ml、(179.68±4.26)ng/ml、(148.69±6.58)ng/L、(762.58±26.58)pg/ml高于IL-12单克隆抗体组(1.62±0.17)分、(472.59±15.64)ng/ml、(106.25±3.27)ng/L、(37.62±2.16)ng/ml、(163.57±3.12)ng/ml、(98.67±5.12)ng/L、(412.68±16.98)pg/ml)和对照组,而结肠重量/长度为(42.36±3.16)mg/cm大于IL-12单克隆抗体组(33.59±2.07)mg/cm)和对照组小鼠;结肠组织中Th2型细胞因子IL-4、IL-10为(55.27±1.62)pg/ml、(90.27±3.68)pg/ml低于IL-12单克隆抗体组(61.27±2.21)pg/ml、(98.67±1.68)pg/ml)和对照组(P<0.05)。结论IL-12单克隆抗体通过改善Th1型细胞因子、Th2型细胞因子的异常表达,对Th1/Th2免疫平衡进行调节,进而抑制克罗恩病的炎症反应,起到治疗的效果。
OBJECTIVE To study the regulating effect of interleukin-12(IL-12)monoclonal antibody on the helper T cell 1/helper T cell 2(Th1/Th2)immune balance in Crohn’s disease model mice.METHODS Totally 30 healthy BALB/c mice were selected and divided into 10 of the normal control group(10 mice)and the 20 of experimental group.The experimental group were treated with crohn’s disease model.After successful modeling,The experimental group with successful modeling were divided into 10 of the crohn’s disease group and 10 of the IL-12 monoclonal antibody group(10 mice each).The IL-12 mAb treatment group were received intraperitoneal injection of IL-12 mAb(25 mg/kg,once per week),and the control group and Crohn disease group were given intraperitoneal injection of 0.2 mL of normal saline.After 4 weeks of treatment,the degree of disease activity,colon weight and colon length of three groups of mice were evaluated.The levels of Th1 cytokine such as interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-8(IL-8),and Th2 cytokines including IL-4,IL-10,IL-12 and IL-23 in the colon tissue of three groups of mice were detected by enzyme-linked immunosorbent assay.RESULTS The scores of disease activity,Th1 cytokines including IFN-γ,TNF-α,IL-1β,IL-8,IL-12 and IL-23 in Crohn’s disease group were(4.12±0.23),(563.49±21.36)ng/ml,(120.69±6.69)ng/L,(43.73±3.58)ng/ml,(179.68±4.26)ng/ml,(148.69±6.58)ng/L and(762.58±26.58)pg/ml,respectively,significantly higher than those in the monoclonal antibody group(1.62±0.17)points,(472.59±15.64)ng/ml,(106.25±3.27)ng/L,(37.62±2.16)ng/ml,(163.57±3.12)ng/ml,(98.67±5.12)ng/L,and(412.68±16.98)pg/ml,respectively and the control group,while the colon weight/length was(42.36±3.16)mg/cm,significantly greater than that of the IL-12 monoclone antibody group(33.59±2.07)mg/cm and the control group mice.The Th2 type cytokines IL-2 in the colon tissue including IL-4 and IL-10 were(55.27±1.62)pg/ml and(90.27±3.68)pg/ml,respectively,significantly lower than that of IL-12 monoclonal antibody group(61.27±2.21)pg/ml and(98.67±1.68)pg/ml,respectively and control group(P<0.05).CONCLUSION IL-12 monoclonal antibody could regulate the immune balance of Th1/Th2 by improving the abnormal expression of Th1 and Th2 cytokines,and then suppressed the inflammatory response of Crohn’s disease and had a therapeutic effect.
作者
杨娟
杨国珍
杨瀚林
汤弘婷
王海燕
杨梅
邓荣
李琴山
YANG Juan;YANG Guo-zhen;YANG Han-lin;TANG Hong-ting;WANG Hai-yan;YANG Mei;DENG Rong;LI Qin-shan(Guizhou Medical University,Guiyang,Guizhou 550004,China;不详)
出处
《中华医院感染学杂志》
CAS
CSCD
北大核心
2020年第4期497-502,共6页
Chinese Journal of Nosocomiology
基金
国家自然科学基金资助项目(81460365,81402451,81760039,81960476)
贵州省科技厅基金资助项目(2019-1270)
贵州医科大学附属医院博士启动基金资助项目(201404)。
作者简介
通讯作者:李琴山,E-mail:282418286@qq.com。
