Cyp4a14基因对小鼠肠炎模型肠道黏膜氧化应激反应的影响  

Effect of Cyp4a14 gene on intestinal mucosal oxidative stress in mice with enteritis

作　　者：肖中岳[1] 轩青霞 高强[1] Xiao Zhongyue;Xuan Qingxia;Gao Qiang(Dept of Oncology,The First Affiliated Hospital,Henan University of Science and Technology,Luoyang 471003;Dept of Ultrasound,Luoyang Maternal and Child Health Hospital,Luoyang 471023)

机构地区：[1]河南科技大学第一附属医院肿瘤科,洛阳471003 [2]洛阳市妇幼保健院超声科,洛阳471023

出　　处：《安徽医科大学学报》2021年第1期38-42,共5页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:81370487)。

摘　　要：目的探讨Cyp4a14基因、丙二醛(MDA)及相关炎症因子对小鼠肠道黏膜氧化应激反应的影响。方法选取雄性Cyp4a14野生型(Cyp4a14^(+/+))和基因敲除纯合型(Cyp4a14^(-/-))小鼠,随机分为Cyp4a14^(+/+)对照组、Cyp4a14^(+/+)DSS组、Cyp4a14^(-/-)对照组、Cyp4a14^(-/-) DSS组。两对照组均给予饮用水自由饮用6 d,两葡聚糖硫酸钠(DSS)组均给予3.0%DSS溶液自由饮用6 d。肠道炎症情况通过体质量变化、疾病活动度(DAI)、结肠长度和HE染色等方法进行综合评估。通过实时定量PCR技术分别检测小鼠结肠组织中炎症因子白细胞介素1β(IL-1β)和肿瘤坏死因子α(TNF-α) mRNA的表达情况,并利用生物化学方法检测血清中MDA浓度评价结肠组织氧化应激程度。结果两对照组均无肠炎表现,Cyp4a14^(-/-) DSS组呈轻度肠炎表现,Cyp4a14^(+/+)DSS组小鼠呈重度肠炎表现。Cyp4a14^(+/+)DSS组和Cyp4a14^(-/-) DSS组小鼠结肠组织中炎症因子IL-1β和TNF-αmRNA在结肠中的表达均升高,且Cyp4a14^(+/+) DSS组较Cyp4a14^(-/-) DSS组进一步升高。MDA在Cyp4a14^(-/-)对照组小鼠血清中浓度较Cyp4a14^(+/+)对照组下降,与两对照组相比,Cyp4a14^(+/+)DSS组和Cyp4a14^(-/-) DSS组小鼠血清MDA浓度均升高,尤以Cyp4a14^(+/+)DSS组升高更显著,四组小鼠之间均有差异(F=573.233,P<0.001)。结论 Cyp4a14基因敲除后小鼠结肠组织脂质过氧化物MDA产生减少,且对DSS诱导的结肠炎敏感性下降,结果提示Cyp4a14基因可能是小鼠结肠组织氧化应激的促进因素,并通过MDA参与炎性反应对肠道组织的损伤。Objective To investigate the effects of Cyp4 a14 gene, Malondialdehyde(MDA) and the related inflammatory factors on intestinal mucosal oxidative stress in mice.Methods Male mice of Cyp4 a14^(+/+) and Cyp4 a14^(-/-) were selected and randomly divided into 4 groups: Cyp4 a14^(+/+) control group, Cyp4 a14^(+/+) DSS group, Cyp4 a14^(-/-) control group, Cyp4 a14^(-/-)DSS group. Both control groups were given cleaning water to drink for 6 days, and both DSS groups were given 3.0% DSS solution to drink for 6 days. Colon inflammation was comprehensive evaluated by changes in constitution/quantity, disease activity index(DAI), colonic length and HE staining. The mRNA levels of pro-inflammation cytokines(IL-1β and TNF-α) were quantified by Real-time PCR. The concentration of MDA in serum was measured by biochemical method to evaluate the degree of oxidative stress.Results There was no signs of enteritis in the two control groups, Cyp4 a14-/- DSS group showed mild enteritis, while Cyp4 a14+/+ DSS group showed severe enteritis. The expressions of IL-1β and TNF-α in the colon increased both in Cyp4 a14^(+/+) DSS group and Cyp4 a14^(-/-) DSS group, and Cyp4 a14^(+/+) DSS group increased more significant than Cyp4 a14^(-/-) DSS group. The serum concentration of MDA in Cyp4 a14-/- control group decreased compared with that in Cyp4 a14^(+/+) control group. Compared with the two control groups, serum MDA concentrations both increased in the Cyp4 a14^(+/+) DSS group and the Cyp4 a14^(-/-) DSS group, especially in the Cyp4 a14^(+/+) DSS group, There were differences among the four groups(F=573.233, P<0.001).Conclusion Lipid peroxides MDA decreases in colon tissues of mouse knockout of Cyp4 a14 gene, and the sensitivity to DSS-induced colitis decreases, suggesting that Cyp4 a14 gene may be a promoter of oxidative stress in colon tissues of mice.

关 键 词：丙二醛 Cyp4a14 炎症性肠病 结肠炎 

分 类 号：R574.62[医药卫生—消化系统]