MNNG亚慢性暴露致大鼠食管损伤及炎性反应机制研究

目的观察MNNG亚慢性暴露对大鼠血清肿瘤坏死因子-α(TNF-α)、白细胞介素6(IL-6)、白介素1β(IL-1β)含量及食管组织结构的影响。方法65只SPF级雄性Wistar大鼠随机分为生理盐水对照组、80、120、160和200μg/ml MNNG染毒组,每组13只。对照组大鼠采用等量生理盐水灌胃,实验组大鼠以80、120、160和200μg/ml MNNG灌胃染毒,同时自由饮用含30μg/ml MNNG的水,持续染毒13周。通过食管组织切片观察大鼠食管组织的结构变化,采用ELISA法测定大鼠血清中TNF-α、IL-1β和IL-6含量,蛋白印迹法(Western blot)检测大鼠食管组织中炎性相关蛋白β-catenin和p-gsk-3α变化。结果大鼠食管组织切片结果显示,MNNG亚慢性暴露可导致大鼠食管粘膜角化、粘膜下出血及食管黏膜广泛糜烂坏死,部分大鼠食管切片中有炎性细胞浸润。与对照组相比,120和160μg/ml MNNG实验组大鼠血清TNF-α、IL-1β明显升高;实验组大鼠血清IL-6含量与对照组相比均明显升高,差异有统计学意义(P<0.05)。MNNG亚慢性暴露组大鼠食管组织中β-catenin和p-gsk-3α的表达量与对照组相比均明显升高(P<0.05)。结论MNNG亚慢性暴露可引起大鼠血清TNF-α、IL-6、IL-1β含量及食管组织结构的明显改变,本研究可为MNNG亚慢性暴露致大鼠食管损伤及炎性反应机制探索提供参考。

Mechanism of esophageal injury and inflammatory response induced by sub-chronic exposure to MNNG in rats

Objective To observe the effects of sub-chronic exposure to MNNG on the contents of serum tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),interleukin-1β(IL-1β),and esophageal tissue structure in rats.Methods Sxity-five SPF-grade male Wistar rats were randomly divided into normal saline control group,80,120,160 and 200μg/ml MNNG groups,13 rats in each group.The rats in the control group were given the same amount of normal saline by gavage.At the same time,they were free to drink water with 30μg/ml MNNG lasting for 13 weeks.The changes of esophageal tissue structure were observed by esophageal tissue section,the levels of TNF-α,IL-1β,and IL-6 in serum were measured by ELISA,the changes of inflammatory-related proteinsβ-catenin and p-gsk-3αin esophageal tissue were detected by Western blot.Results The result of esophageal tissue sections showed that sub-chronic exposure to MNNG could lead to esophageal mucosal keratinization,submucosal hemorrhage,extensive erosion and necrosis of esophageal mucosa in rats,and inflammatory cell infiltration was found in some esophageal sections.Compared with the control group,the levels of serum TNF-α and IL-1β in 120 and 160μg/ml MNNG experimental groups were significantly higher than those in the control group,and the levels of serum IL-6 in the experimental group were significantly higher than those in the control group.Compared with the control group,the expression of β-catenin and p-gsk-3α in the esophageal tissue of rats exposed to MNNG were significantly increased(P<0.05).Conclusion Sub-chronic MNNG exposure can cause significant changes in serum levels of TNF-α,IL-6,IL-1β,and esophageal tissue structure in rats.This study can provide a reference for exploring the mechanism of esophageal injury and inflammatory response induced by sub-chronic MNNG exposure.