(中国辐射防护研究院药物安全性评价中心,药物毒理与放射损伤药物山西省重点实验室,中核放射毒理与放射性药物临床前评价重点实验室,太原 030006)
Q95-33
(Drug Safety Evaluation Center of China Institute for Radiation Protection,Shanxi Key Laboratory of Drug Toxicology and Drug for Radiation Injury, CNNC Key Laboratory on Radiotoxicology and Radiopharmaceutical Preclinical Evaluation, Taiyuan 030006, China)
目的 探讨亚低温治疗对放射性肺损伤的防护作用,并与临床常用抗辐射药氨磷汀比较防护效果?方法 75 只雄性SD 大鼠随机分为空白对照组?单纯照射组?氨磷汀阳性对照组?亚低温预防组及亚低温治疗组?除空白对照组外其余组均接受20 Gy 电子线全胸单次照射,氨磷汀阳性组在照射前30 min 腹腔注射氨磷汀;亚低温预防组大鼠体温降至亚低温状态后进行射线照射,并维持6 h;亚低温治疗组大鼠接受照射后将体温保持在亚低温状态并持续6 h?在照射后当天?第14 天及第35 天做肺组织病理组织学检测及胶原纤维检测,测定大鼠血清中丙二醛(MDA)含量,还原型谷胱甘肽(GSH)含量及超氧化物歧化酶活性(SOD),检测肺组织匀浆中TNF?α 含量,并观察肺组织凋亡情况?结果 照射后各受照组SOD 活性立即降低,第14 天时亚低温治疗组的SOD 活性高于单纯照射组( P < 0. 05);与单纯照射组比较,氨磷汀阳性组及亚低温干预组第14 天血清中MDA 含量均显著降低( P < 0. 05);照射后6 h 单纯照射组TNF?α 含量显著升高,氨磷汀阳性组及亚低温治疗组与单纯照射组相比,上升程度较低( P < 0. 05);照射当天单纯照射组凋亡细胞大量增多且分布广泛,各干预组都相应减少,但组间差异不明显?结论 亚低温治疗能提高放射性肺损伤大鼠的抗氧化能力?抗炎症能力及抗凋亡能力,与临床常用药氨磷汀作用效果相近?
Objective To investigate the protective effect of mild hypothermia on radiation?induced lung injury, and to compare the differences with the clinically used drug amifostine. Methods Seventy?five male Sprague Dawley rats were randomly divided into control, irradiation, amifostine, mild hypothermia prevention, and mild hypothermia treatment groups. All groups (except the control group) received a single?dose 20 Gy electron?beam full?chest irradiation. The amifostine group received an intraperitoneal amifostine injection(150 mg/ kg)at 30 min before irradiation. The hypothermia prevention group received mild body cooling initiated prior to irradiation(34 ±1℃)and continued for 6 h. The hypothermia treatment group received mild body cooling immediately after irradiation and continued for 6 h. Lung tissues were examined by histopathology and for collagen content. Serum levels of malondialdehyde and glutathione, and superoxide dismutase (SOD) activity, were examined at 14 d and 35 d after irradiation. Tumor necrosis factor α levels in the lung tissue homogenates, and apoptosis in the lung tissues, were also examined. Results Serum SOD activity decreased immediately after irradiation, and was significantly recovered in the mild hypothermia treatment group at 14 d recovery compared with the irradiation group ( P < 0. 05). Malondialdehyde content in the amifostine group and mild hypothermia intervention group were lower than the irradiation group at 14 d recovery ( P < 0. 05). TNF?α levels in the irradiation group were significantly increased at 6 h after irradiation, but were significantly reduced in the amifostine group and mild hypothermia treatment group ( P < 0. 05). Numbers of apoptotic cells in the irradiation group were significantly increased and widely distributed in the irradiation group, but were reduced in all intervention groups (there were no differences between the intervention groups). Conclusions Mild hypothermia can provide antioxidant, anti?inflammatory, and anti?apoptotic effects following radiation?induced lung injury in rats, to levels similar to that using the clinical drug amifostine.
王远飞,李曙芳,王新钢,王永丽,许文黎,黄立群,岳娟,安全.亚低温对放射性肺损伤大鼠的保护作用[J].中国实验动物学报,2018,26(5):624~630.
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