西咪替丁对胸部分割照射小鼠脾脏损伤的治疗作用

Therapy effect of cimetidine on spleen of mice irradiated with thoracic fractionated irradiation

目的探究西咪替丁(CMTD)对局部分割照射小鼠的治疗作用。方法雄性C57BL/6小鼠30只,随机单位组设计分为对照组、单纯照射组和照射给药组(CMTD,100 mg/kg),每组10只;采用X射线局部分割照射小鼠右胸腔,8 Gy/d照射,连续3 d,累积照射剂量为24 Gy,剂量率为0.883 Gy/min。照射后连续7 d给予照射给药组小鼠灌胃CMTD(100 mg·kg^-1·d^-1),对照组和单纯照射组给予生理盐水。照射后第7天检测小鼠体重、脏器指数、脾脏T淋巴细胞亚群、B淋巴细胞亚群、NK细胞亚群变化以及脾脏组织病理学改变。结果分割照射对小鼠体重影响不大,但可诱发远端效应,使脾脏脏器指数降低为(0.369±0.011),与对照组的(0.396±0.022)比较,差异有统计学意义(t=2.978,P<0.05);改变脾脏病理结构,脾脏CD3+、CD4+、CD8+、CD3+CD4+、CD3+CD8+淋巴细胞比例显著降低(t=5.754、3.570、4.442、5.281、4.570,P<0.05)。而照射给药组小鼠体重恢复明显,脾脏组织损伤缓解,脾脏淋巴细胞亚群比例恢复,CD3+、CD3+CD4+、CD3+CD8+淋巴细胞显著升高(t=3.523、2.706、2.520,P<0.05),但仍低于正常水平。结论CMTD可有效改善X射线分割照射对小鼠脾脏的损伤,提高照后小鼠的免疫功能,可作为潜在的抗辐射治疗药物。

Objective To investigate the protective effect of cimetidine on mice with fractionated X-ray irradiation through right thorax.Methods Thirty male C57BL/6 mice were randomly divided into control group,irradiation group and irradiation+cimetidine group(100 mg/kg),10 mice in each group.Mice right thorax was locally irradiated with X-rays at a dose rate of 0.883 Gy/min to a cumulative dose of 24 Gy,8 Gy per day in 3 d.After irradiation,the irradiation+cimetidine group was given cimetidine(100 mg·kg^-1·d^-1)for 7 d consecutively,and Ctrl and IR groups were given saline.Seven days after irradiation,the mice weight,spleen index and its T lymphocytes,B lymphocytes and NK cells were measured.Spleen tissue was stained with HE for pathological observation.Results The fractionated irradiation lightly suppressed mice growth but obviously induced abscopal damage on spleen so that the spleen index were decreased.The irradiation group(0.369±0.011)had statistically significant difference compared with the control group(0.396±0.022)(t=2.978,P<0.05),the spleen pathological structure became disorder,and the percentages of CD3+,CD4+,CD3+CD4+,CD3+CD8+lymphocytes in spleen were decreased significantly(t=5.754,3.570,4.442,5.281,4.570,P<0.05).Cimetidine could partially restore the weight of irradiated mice,relieved spleen structure damage and effectively restored lymphocyte subsets,and partly recovered the levels of CD3+,CD3+CD4+,CD3+CD8+lymphocytes in the spleen(t=3.523,2.706,2.520,P<0.05).Conclusions Cimetidine,as a potential radiation protection drug,could effectively reduce the mouse spleen injury induced by X-ray fractionated irradiation by improving mouse immune function.