金雀异黄素对三硝基苯磺酸诱导的结肠炎小鼠的干预作用及其可能机制  

Intervention effect of genistein on mice with trinitrobenzene-sulfonic acid-induced colitis and its possible mechanism

作　　者：张怡华 吕晓丹[2] 曾睿智 韩冰 张维维[1] 徐小芳 陈如艳 叶卫政 陈晓战 范俊华[1] 詹灵凌[2] 吕小平[1] ZHANG Yi-hua;LYU Xiao-dan;ZENG Rui-zhi;HAN Bing;ZHANG Wei-wei;XU Xiao-fang;CHEN Ru-yan;YE Wei-zheng;CHEN Xiao-zhan;FAN Jun-hua;ZHAN Ling-ling;LYU Xiao-ping(Department of Gastroenterology,the First Affiliated Hospital of Guangxi Medical University,Nanning 530021,China;Department of Clinical Laboratory,the First Affiliated Hospital of Guangxi Medical University,Nanning 530021,China)

机构地区：[1]广西医科大学第一附属医院消化内科,南宁市530021 [2]广西医科大学第一附属医院检验科,南宁市530021

出　　处：《广西医学》2022年第7期739-744,共6页Guangxi Medical Journal

基　　金：国家自然科学基金(81860104);广西医疗卫生适宜技术开发与推广应用项目(S2018049);广西壮族自治区卫生健康委员会项目(Z20200398)。

摘　　要：目的分析金雀异黄素(GEN)对三硝基苯磺酸(TNBS)诱导的结肠炎小鼠的干预作用,并探讨其可能的作用机制。方法将32只C57BL/6雄性小鼠随机分为正常对照组、模型组、柳氮磺砒啶组和GEN组,每组8只。除正常对照组外,其他3组均采用TNBS法建立结肠炎小鼠模型。造模第2天,给予正常对照组、模型组生理盐水灌胃,对柳氮磺砒啶组、GEN组分别给予柳氮磺砒啶、GEN灌胃。造模后第2天评估各组小鼠的疾病活动指数(DAI),于干预7 d后处死小鼠,测量结肠长度,评估结肠大体形态损伤指数(CMDI),镜下观察结肠组织病理变化,检测血清白细胞介素(IL)-1β、IL-10、肿瘤坏死因子(TNF)-α水平及结肠组织核因子κB抑制蛋白α(IκB-α)和p65蛋白表达量。结果造模后,除正常对照组外,其他组小鼠开始出现大便异常,体重下降,但在药物干预后7 d柳氮磺砒啶组、GEN组小鼠上述情况逐渐减轻。与正常对照组相比,模型组小鼠结肠缩短,结肠组织中炎症细胞浸润明显,DAI和CMDI均升高,血清IL-1β、TNF-α水平升高,血清IL-10水平降低,结肠组织IκB-α、p65蛋白相对表达量上调(均P<0.05)。与模型组相比,柳氮磺砒啶组、GEN组小鼠结肠长度延长,结肠组织中炎症细胞浸润减轻,DAI和CMDI均降低,血清IL-1β、TNF-α水平下降,血清IL-10水平升高,结肠组织IκB-α、p65蛋白相对表达量下调(均P<0.05)。结论GEN可缓解TNBS诱导的结肠炎小鼠的炎症症状和结肠损伤情况,其作用机制可能与抑制核因子κB信号通路从而发挥抗炎作用有关。Objective To analyze the intervention effect of genistein(GEN) on mice with colitis induced by trinitrobenzene-sulfonic acid(TNBS), and to investigate its possible mechanism of action. Methods Thirty-two male C57 BL/6 mice were randomly divided into normal control group, model group, sulfasalazine group and GEN group, with eight mice in each group. Except for the normal control group, the other three groups employed the TNBS method to establish mouse models of colitis. On the second day of modeling, the normal control and model groups were given normal saline by gavage, and the sulfasalazine group and the GEN group were intragastrically given sulfasalazine and GEN, respectively. Mice′s disease activity index(DAI) was assessed in each group on the second day after modeling. After seven days of the intervention, the mice were sacrificed to measure the length of the colon, the Colon Macroscopic Damage Index(CMDI) was evaluated, the pathological changes in colon tissues were observed under the microscope, and serum levels of interleukin(IL)-1β, IL-10, and tumor necrosis factor(TNF)-α, as well as the expression of inhibitor of nuclear factor κB α(IκB-α) and p65 proteins in colon tissues were detected. Results After modeling, except for the normal control group, mice in the other groups began to sustain abnormal defecation and weight loss;however, seven days after drug intervention, the aforementioned conditions were attenuated gradually in mice of the sulfasalazine and GEN groups. Compared with those in the normal model group, mice in the model group exhibited decreased colon length, obvious inflammatory cell infiltration in colon tissues, elevated DAI and CMDI, higher serum levels of IL-1β and TNF-α, a reduced serum IL-10 level, and up-regulated relative expression of IκB-α and p65 proteins in colon tissues(all P<0.05). Compared with those in the model group, mice in the sulfasalazine and GEN groups had prolonged colon lengths, decreased inflammatory cell infiltration in colon tissues, reduced DAI and CMD

关 键 词：炎症性肠病 金雀异黄素 三硝基苯磺酸 结肠炎 炎症反应 核因子ΚB信号通路 小鼠 

分 类 号：R574.62[医药卫生—消化系统]