FBW7基因敲除的放射诱导性胃肠综合征小鼠肠道损伤变化及其机制  

Changes of intestinal damage in FBW7 deletion mice with radiation-induced gastrointestinal syndrome

作　　者：章屹然 王兆熹 彭涵 朱军 张健 李惠晨 ZHANG Yiran;WANG Zhaoxi;PENG Han;ZHU Jun;ZHANG Jian;LI Huichen(School of Basic Medicine,Air Force Military Medical University,Xi'an 710032,China;不详)

机构地区：[1]空军军医大学基础医学院,西安710032 [2]空军军医大学西京医院整形外科 [3]空军军医大学西京医院消化外科

出　　处：《山东医药》2022年第20期41-45,共5页Shandong Medical Journal

基　　金：陕西省自然科学基础研究计划一般项目(2022JQ-894)。

摘　　要：目的观察FBW7基因敲除的放射诱导性胃肠综合征(GIS)小鼠肠道损伤变化,并探讨相关机制。方法野生型雄性C57/BL小鼠15只纳入对照组,另选15只通过Cre/loxp系统进行FBW7肠道特异性基因敲除,作为实验组。对两组小鼠进行60Go全身照射,照射剂量为8 Gy,建立GIS模型。比较两组小鼠的存活时间、体质量改变情况和腹泻情况以评价放射损伤;观察两组小鼠小肠段组织病理学情况,测量小肠绒毛长度、隐窝深度及小肠上皮细胞髓过氧化物酶(MPO)活性;采用ELISA法检测两组小肠上皮细胞中的IL-1β、IL-6、TNF-α;采用免疫组化染色观察并计数Ki-67、PCNA阳性细胞以反映肠道细胞增殖情况;采用TUNEL免疫荧光染色观察小肠上皮细胞凋亡情况,采用免疫组化法检测小肠上皮细胞中的Caspase-3、Bax蛋白。结果与对照组相比,实验组存活时间更长,体质量下降更快,腹泻评分降低,小肠组织病理学评分降低,肠道绒毛长度及小肠隐窝深度增高(P均<0.05)。实验组小肠上皮细胞MPO活性及IL-1β、IL-6、TNF-α表达低于对照组(P均<0.05)。实验组Ki-67、PCNA阳性细胞数量多于对照组,小肠上皮细胞凋亡数及Caspase-3、Bax蛋白相对表达量低于对照组(P均<0.05)。结论肠道FBW7基因敲除的GIS小鼠放射性肠道损伤程度减轻,炎症反应减轻,其机制可能与抑制小肠上皮细胞凋亡、促进肠道隐窝干细胞增殖有关。Objective To observe the changes of intestinal damage in FBW7 deletion mice with radiation-induced gastrointestinal syndrome(GIS)and to explore the related mechanisms.Methods Fifteen wild-type male C57/BL mice were included in the control group,while another 15 mice were selected for FBW7 deletion by the Cre/loxp system as the experimental group.The mice of the two groups were irradiated with 60Go whole body with a radiation dose of 8 Gy to estab-lish the GIS models.The evaluation of radiation damage was carried out by comparing average survival time,weight change of the mice and diarrhea of mice in the two groups,respectively.We observed the histopathological condition of the small intestine,the length of intestinal villi and crypt depth,and myeloperoxidase(MPO)expression level in small intesti-nal epithelial cells.We detected the expression levels of interleukin-1β(IL-1β),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in the small intestinal epithelial cells by ELISA.We observed and calculated Ki67 and proliferating cell nuclear antigen(PCNA)positive cells by immunohistochemical staining to reflect the proliferation ability of intestinal cells in the two groups.We observed the apoptosis of intestinal epithelial cells by TUNEL immunofluorescence staining,and de-tected Caspase-3 and Bax proteins in intestinal epithelial cells by immunohistochemistry.Results The experimental group had longer survival time,faster weight loss,lower diarrhea score,lower intestinal histopathological scores,and in-creased intestinal villus length and intestinal crypt depth than the control group(all P<0.05).The activity of MPO and the expression levels of IL-1β,IL-6 and TNF-αin the experimental group were lower than those in the control group(all P<0.05).The numbers of Ki-67 and PCNA positive cells were larger while the relative expression levels of Caspase-3 and Bax proteins were lower in the experimental group than in the control group(all P<0.05).Conclusion FBW7 deletion may significantly reduce the degree of radiation-i

关 键 词：FBW7基因 泛素连接酶复合体 辐射损伤 胃肠综合征 放射疗法 

分 类 号：R730.5[医药卫生—肿瘤]