目的 研究西咪替丁对低剂量累积电离辐射比格犬脾组织病理变化及其对脾组织超氧化物歧化酶2(SOD2)、谷胱甘肽过氧化酶1(GPX1)蛋白和基因表达的影响,探讨西咪替丁对低剂量辐射损伤防护作用的可能机制。方法 取24只雄性比格犬,每组4只,共6组,分别为正常对照组,模型组,阳性药对照组,西咪替丁低、中、高剂量组(5.33,10.67,21.33 mg·kg-1),采用60Co-γ射线连续全身照射23 d,剂量率为0.040 8 mGy·min-1,西咪替丁于照射期间连续灌胃给药每天1 次。采用显微镜观察脾组织形态学和超微结构的改变;采用qRT-PCR 和免疫组化技术,检测受照射犬脾组织中SOD2、GPX1基因和蛋白的表达水平。结果 与模型对照组相比,西咪替丁组的脾组织形态学和超微结构病变有改善;与模型对照组相比,西咪替丁低剂量组、中剂量组、高剂量组脾组织中SOD2、GPX1蛋白表达均升高(P<0.05),同时西咪替丁各剂量组脾细胞中SOD2、GPX1基因mRNA水平均升高并具有极显著性差异(P<0.01)。结论 西咪替丁对脾组织的病理变化有明显改善作用,可显著提高脾组织中SOD2、GPX1基因和蛋白的表达水平,对低剂量辐射导致的氧化损伤具有较好的防护作用。
Abstract
OBJECTIVE To study the effect of cimetidine on the histopathology and the expression of SOD2, GPX1 gene and protein in low-dose accumulative irradiated Beagle dogs spleen and to investigate the mechanism of cimetidine′s protective effect on low-dose accumulative irradiation. METHODS Twenty-four male Beagle dogs were divided into six groups: normal control group,model group,positive drug control group and cimetidine groups at the dose of 5.33, 10.67, 21.33 mg·kg-1 respectively. The dogs were irradiated with 60Co-γ-ray at 0.040 8 mGy·min-1 rate for 23 d. Cimitidine was administered intragastrically during irradiation, once a day. Microscope was adopted to observe the pathologic change of spleen and the expression levels of SOD2,GPX1 gene and protein in the spleen tissue of dogs were detected by qRT-PCR and immunohistochemistry techniques. RESULTS Compared with the model group,cimetidine ameliorated the pathological changes and ultrastructure lesions in the spleen of dogs. Also compared with the model group, the levels of SOD2 and GPX1 protein in cimetidine groups at the dose of 5.33, 10.67, 21.33 mg·kg-1 were higher(P<0.05) and the levels of SOD2 and GPX1 mRNA of the three cimetidine groups were increased significantly(P<0.01). CONCLUSION Cimetidine can reduce the histological damage. Cimetidine can upregulate the expressions of SOD2 and GPX1 gene and protein and it has good protective effect on the antioxidant system injury.
关键词
西咪替丁 /
低剂量辐射 /
比格犬 /
超氧化物歧化酶2 /
谷胱甘肽过氧化酶1
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Key words
cimetidine /
low-dose radiation /
Beagle dog /
SOD2 /
GPX1
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中图分类号:
R963
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参考文献
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脚注
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基金
国家科技重大专项重大新药创制项目资助(2014ZX09J14103-07B)
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