12-氧-十四烷酰佛波醇-13-癸酰酯对小鼠肠道急性放射损伤的保护作用及机制研究

摘要

目的 研究12-氧-十四烷酰佛波醇-13-癸酰酯(TPD)对小鼠肠道急性放射损伤的保护作用及其机制.方法 将20只6~8周雌性BALB/c小鼠随机分为4组:对照组、TPD组(25、50、100 μg/kg),10 Gy 60Co γ射线全身照射造成小鼠急性肠道放射损伤模型,TPD组照射前经尾静脉连续给药3 d,观察小鼠照射后20 d的生存时间,并用相同方法测定照射后3.5 d隐窝数量.大鼠小肠隐窝上皮细胞(IEC-6)给予1 nmol/L TPD作用12 h后经10 Gy 60 Co γ射线照射,应用CCK-8法检测照射后0、1、2、3、4 d细胞增殖情况.结果 对照组小鼠平均存活4.2 d,最佳给药组(100 μg/kg)平均存活时间为10 d;对照组和最佳给药组平均隐窝数量分别为(11.0 ±1.3)个、(35.1 ±1.9)个;连续测定4 d IEC-6增殖活性,给药组平均D值明显高于对照组.结论 TPD对小鼠肠道急性放射损伤有保护作用,其保护作用机制可能是通过促进小肠隐窝上皮细胞增殖、增加小肠隐窝数量来实现.%Objective To investigate the effect of 12-O-tetradecanoylophorbol-13-decanoate(TPD)on protection against acute intestinal radiation injury of mice and the possible mechanism.Methods Twenty female BALB/c mice aged 6-8 weeks were divided by random number table method into the control group and TPD groups(25,50,and 100 μg/kg). A radiation-damaged model of mice was irradiated by 10 Gy 60Co γ-rays,while the TPD groups were pretreated for 3 d with caudal vein injection before irradiation.The survival time of 20 days and the number of crypts at 3.5 days after irradiation were detected.Rat intestinal epithelial cells(IEC-6)were treated with 1 nmol/L TPD for 12 h before irradiation with 10 Gy 60Co γ-rays,and CCK-8 was used to detect the capability of cell proliferation at 0,1,2,3 and 4 d after irradiation. Results The mice in the control group survived for an average of 4.2 days,compared to 10 days in the optimal TPD group (100 μg/kg).The average number of crypts in the control group and the best TPD group was 11.0 ±1.3 and 35.1 ±1.9 respectively.The proliferation activity of IEC-6 was measured for four consecutive days.The average D value of the TPD groups was significantly higher than that of control.Conclusion TPD has a protective effect against acute intestinal radiation injury, and its protective mechanism may be achieved by promoting intestinal crypt cell proliferation and increasing the number of crypts in the intestine.