机构地区:[1]贵州医科大学医学检验学院,贵州贵阳550004 [2]贵州医科大学附属医院贵州省产前诊断中心,贵州贵阳550004 [3]贵阳市妇幼保健院,贵州贵阳550001 [4]毕节市中医院心内科,贵州毕节551700 [5]毕节市第一人民医院眼科,贵州毕节551700
出 处:《中华医院感染学杂志》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)。
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 th
关 键 词:白细胞介素-12单克隆抗体 克罗恩病 小鼠模型 TH1型细胞因子 TH2型细胞因子
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