吴茱萸碱对急性放射性肠炎肠黏膜的保护作用及机制

摘要

Objective:To investigate the effects and mechanisms of evodiamine on scute radiation enteritis models and intestinal mucosal barrier. Methods:Totally 50 healthy male mice were randomly divided into normal group(N group),model group(M group),evodiamine prevention and treatment group(PT group),evodiamine treatment group (T group),Simida group(S group). PT group had been given evodiamine for one week in advance. Except N group, the other groups were given a single dose of 6Gy 6MV of higher - energy X - rays on the obdominal region to establish acute radiation enteritis models. Twelve hours later,PT group,T group,S group were given intragastric administration for one week. The morphologic indexes were measured by light microscopy and image analysis system. NF - κB p65 protein was measured by immunohistochemistry,TNF - α was measured by ELISA. Results:PT group,T group,S group had significantly higher levels of crypt depth,thickness of mucosa and entire than M group(P < 0. 01). PT group,T group,S group had significantly decreased NF - κB p65 protein levels(P < 0. 01)and TNF - α activities(P< 0. 01). There were significant differences between PT group and T group,S group(P < 0. 05),no differences be-tween T group and S group(P > 0. 05). Conclusion:Evodiamine could significantly increase levels of crypt depth, thickness of mucosa and entire,protect the intestinal mucosa. Evodiamine reduced NF - κB p65 protein expression levels and TNF - α activities in intestinal tissue. These effects of evodiamine related to timing of administration and length of time,beginning prophylaxis administration before the start of radiation therapy played a stronger role on sup-pressing the inflammatory response than simply therapeutic administration.%目的：探讨吴茱萸碱对急性放射性肠炎疗效及对肠黏膜屏障保护的机制。方法：清洁级小鼠50只，随机分为正常组、模型组、吴茱萸碱预防加治疗组（简称预治组）、吴茱萸碱治疗组（简称治疗组）、思密达组。预治组提前灌胃给药1周。除正常组外的各组采用高能 X 射线照射，总剂量6Gy，建立急性放射性肠炎模型。照射后12h 连续灌胃给药1周。光学显微镜下观察及图像分析软件测定其相关形态学指标，并免疫组化法测定肠组织 NF -κB p65蛋白活性，ELISA 法测定肿瘤坏死因子α（TNF -α）含量。结果：各给药组小鼠肠组织隐窝深度、黏膜及全层壁厚度均显著高于模型组（P <0.01）。NF -κB p65蛋白表达（P <0.01）、TNF -α含量（P <0.01）显著低于模型组。预治组好于治疗组和思密达组，差异有统计学意义（P <0.05）。治疗组与思密达组比较差异没有统计学意义（P >0.05）。结论：吴茱萸碱可明显升高放射性肠炎肠组织隐窝深度、黏膜及全层壁厚度，降低其 NF -κB p65蛋白表达，降低 TNF -α含量。吴茱萸碱上述作用与给药时机和时间相关，放射治疗前即开始预防性用药比单纯治疗给药保护肠黏膜的作用更强。