西咪替丁对低剂量累积照射比格犬肝组织中SOD_2和GPX_1表达的影响

Effect of cimetidine on the expression of SOD_2 and GPX_1 in low-dose accumulatively irradiated beagle dogs

目的:探讨西咪替丁对低剂量电离辐射比格犬肝组织中SOD_2,GPX_1基因和蛋白表达水平的影响。方法:雄性比格犬24只,分为6组,每组4只,分别为正常对照组、模型对照组、阳性药对照组、西咪替丁低、中、高剂量组,采用60Co-γ射线连续全身照射23 d,每天照射18 h,剂量率为0. 040 8 m Gy·min^(-1),西咪替丁于照射期间连续灌胃(ig)给药,qd。采用qRT-PCR和免疫组化技术,检测受照射犬肝组织中SOD_2,GPX_1基因和蛋白的表达水平。结果:与模型对照组相比,西咪替丁3个剂量组(5. 33,10. 67和21. 33 mg·kg^(-1))显示出不同的效果,西咪替丁中剂量组、高剂量组肝组织中SOD_2蛋白表达均升高(P <0. 05),各剂量组肝细胞中SOD_2基因mRNA水平均升高并具有极显著性差异(P <0. 01);与模型对照组相比,西咪替丁各组肝脏中GPX_1基因mRNA和蛋白表达均显著升高(P <0. 01)。结论:西咪替丁可显著提高肝组织中SOD_2,GPX_1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。

Objective: To investigate the effect of cimetidine on the expression of SOD2,GPX1 gene and protein in low-dose accumulatively irradiated beagle dogs. Methods: Twenty-four male Beagle dogs were divided into six groups,4 in each group: normal control group,model group,positive group and cimetidine high,middle and low dose groups. The dogs were irradiated with60 Co-γ-ray at 0. 040 8 m Gy·min^-1 rate for 23 days,18 hours each day. Cimitidine was administered intragastrically during irradiation,once a day. The expression levels of SOD2,GPX1 gene and protein in the liver tissue of dogs were detected by qRT-PCR and immunohistochemistry techniques.Results: Compared with the model group,cimetidine groups at the dose of 5. 33,10. 67 and 21. 33 mg·kg^-1 respectively show different results. The level of SOD2 protein of cimetidine groups at the dose of 10. 67 and 21. 33 mg·kg-1 was higher(P < 0. 05) and the levels of SOD2 mRNA of the three cimetidine groups were increased significantly(P < 0. 01). Compared with the model group,the levels of GPX1 protein and mRNA of the three cimetidine groups were also increased significantly(P < 0. 01). Conclusion: Cimetidine can upregulate the expression of SOD2,GPX1 gene and protein and it has good protective effect on antioxidant-induced system injury.