吴茱萸碱对急性放射性肠炎疗效及相关机制实验研究

Therapeutic Effect of Evodiamine on Acute Radiation Enteritis and Possible Mechanisms

目的:探讨吴茱萸碱对急性放射性肠炎疗效及可能的机制。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+治疗组、吴茱萸碱治疗组、思密达组。吴茱萸碱预防加治疗组提前灌胃给药1周,除正常组外的各组采用高能X射线照射,总剂量6 Gy建立急性放射性肠炎模型,照射后12h连续灌胃给药1周,光学显微镜下观察并进行组织学评分,并测定组织中IL-6相关基因m RNA水平及DAO含量。结果:各给药组小鼠肠组织组织学评分均显著好于模型组(P<0.01);肠组织IL-6相关基因m RNA水平、肠组织DAO含量显著好于模型组(P<0.01);吴茱萸碱预防+治疗组好于吴茱萸碱治疗组和思密达组两组,差异有统计学意义(P<0.05);吴茱萸碱治疗组与思密达组比较,IL-6相关基因m RNA水平好于思密达组(P<0.05),其余指标差异没有统计学意义(P>0.05)。结论:吴茱萸碱可明显改善放射性肠炎肠组织组织学评分,降低其L-6相关基因m RNA水平,升高肠组织DAO含量,吴茱萸碱上述作用与给药时机和时间相关,开始放射治疗前即开始预防性用药比单纯治疗给药抑制炎症反应的作用更强。

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, model group, evodiamine prevention and treatment group, evodiamine treatment group, Simida group. Evodiamine prevention and treatment group had been given evodiamine for one week in advance. Except normal group, the other groups were given a single dose of 6 Gy of higher-energy X-rays on the obdominal region to establish acute radiation enteritis models. Twelve hours later, evodiamine prevention and treatment group, evodiamine treatment group, Simida group were given intragastric administration for one week. The morphologic indexes were measured by light microscopy and histologic grading. IL-6 related genes mRNA was measured by RT-PCR, DAO was measured by spectrophotometric method. Results： Evodiamine prevention and treatment group, evodiamine treatment group, Simida group had significantly better histologie grading than model group （P〈0.01）. Evodiamine prevention and treatment group, evodiamine treatment group, Simida group had significantly decreased IL-6 related genes mRNA levels （P〈0.01） and rised DAO levels （P〈0.01）. There were significantly differences between evodiamine prevention and treatment group and evodiamine treatment group, Simida group （ P〈0.05 ）. Except IL-6 related genes rnRNA levels （P〈0.05）, there were no differences between evodiamine treatment group and Simida group （ P〉0.05 ）. Conclusion ： Evodiamine could significantly improve histologic grading, protect the intestinal mucosa. Evodiamine reduced IL-6 related genes mRNA levels and rised DAO levels 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 suppressing the inflammatory response than simply therapeutic administration.