观察西咪替丁对低剂量率累积照射比格犬脾脏细胞凋亡及凋亡相关蛋白表达的影响,探讨其辐射保护作用机制.雄性比格犬24只,平均分为6组: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(5.33、10.67、21.33 mg/kg),采用60Co γ射线连续全身照射23 d,剂量率为0.040 8 mGy/min.西咪替丁于照射期间连续灌胃给药,每天1次.累积受照991.44 mGy时,采用TUNEL法检测西咪替丁对照射后比格犬脾脏细胞凋亡的影响,同时用免疫组织化学法检测各组脾脏细胞凋亡相关蛋白P53、Bcl-2、Bax和Caspase-3的表达.结果表明:高剂量西咪替丁能明显抑制照射诱导的脾脏细胞凋亡;西咪替丁能促进脾脏细胞中Bcl-2的表达,明显降低Bax、Caspase-3和P53的表达.推测西咪替丁可能通过升高比格犬脾脏细胞Bcl-2的表达,降低Bax、Caspase-3和P53的表达来抑制细胞凋亡,对脾脏免受低剂量率累积照射的损伤具有较好的辐射保护作用.%ABSTRACT The aim of this study was to investigate the effect of cimetidine on spleen cell apoptosis and the expression of apoptosis-related proteins in Beagle dogs exposed to low-dose-rate radiation and to explore its mechanism of radioprotection. Twenty-four male Beagle dogs were divided into six groups: normal control group, model group, positive control group, and cimetidine-treated groups at doses of 5.33, 10.67, and 21.33 mg/kg. The dogs were irradiated with 60Co γ-rays at a rate of 0.040 8 mGy/min for 23 d. Cimetidine was administered intragastrically once daily during the irradiation period. At cumulative dose of 991.44 mGy, the apoptosis of spleen cells was observed by the TUNEL assay, and the expression of Bcl-2, Bax, and P53 in the spleen was detected by immunohistochemistry. A high dose of cimetidine significantly inhibited spleen cell apoptosis induced by irradiation. In addition, the expression of Bcl-2 in the spleen increased in the cimetidine groups. Moreover, the expression of Bax, caspase-3, and P53 was reduced and the change was statistically significant in the cimetidine groups. Cimetidine induced the expression of Bcl-2 and reduced the expression of Bax, caspase-3, and P53 in the spleen cells of Beagle dogs, thereby inhibiting apoptosis and protecting the spleen from cumulative exposure to low-dose-rate radiation.
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