染料木素羟丙基-β-环糊精包合物的制备及其对睾丸电离辐射损伤的保护作用  

Preparation of genistein hydroxypropyl-β-cyclodextrin inclusion complexes and their protective role against testis ionizing radiation injuries

作　　者：葛焕焕 何磊 王增禄 张英起 郝强 李萌 王征[1] 张存 GE Huanhuan;HE Lei;WANG Zenglu;ZHANG Yingqi;HAO Qiang;LI Meng;WANG Zheng;ZHANG Cun(Co-construction Collaborative Innovation Center for Chinese Medicine Resources Industrialization by Shaanxi&Education Ministry,Shaanxi University of Chinese Medicine,Xianyang 712046,China;Department of Biopharmaceutics,School of Pharmacy,Air Force Medical University)

机构地区：[1]陕西中医药大学陕西中药资源产业化省部共建协同创新中心,咸阳712046 [2]空军军医大学药学系生物制药学教研室

出　　处：《山西医科大学学报》2023年第1期83-89,共7页Journal of Shanxi Medical University

基　　金：陕西省自然科学基础研究计划项目-杰出青年科学基金项目(2022JC-53)。

摘　　要：目的制备染料木素羟丙基-β-环糊精包合物,并探究包合物能否提高染料木素对睾丸电离辐射损伤的保护作用。方法使用超声法按染料木素与β-环糊精的摩尔比为1∶2,1∶2.5和1∶3制备包合物,通过高效液相色谱法、水中溶解度测定、显微镜成像法和扫描电子显微镜观察法对其进行表征。60只雄性C57BL/6小鼠随机分为正常对照组、单独照射组、包合物低、中、高剂量组(分别以35,70,140 mg/kg的包合物灌胃)、染料木素混悬液组(70 mg/kg的染料木素灌胃),每组10只;另选取30只C57B/L雄性小鼠进行生育实验,随机分为正常对照组、单独照射组和包合物组(140 mg/kg的包合物灌胃)。单独照射组、包合物低、中、高剂量组和染料木素混悬液组小鼠均接受4 Gy X射线一次全身辐射。各治疗组给予相应剂量的药物灌胃,每天1次,辐射前和辐射后分别连续给药2周。辐射后21 d观察睾丸组织病理变化,检测精子活力。辐射后36 d开始将生育实验的各组雄鼠与正常雌鼠连续合笼,记录受孕率和窝仔数。结果当染料木素与羟丙基β-环糊精的摩尔比为1∶3时制备的包合物包合率最高,3批次的包合率分别为94.49%,92.87%和91.63%,溶解度提高了405倍,显微镜成像图片与扫描电子显微镜图片均提示包合物与物理混合物在结构和微观形貌上均有着明显差异,说明包合物制备成功。睾丸组织病理结果显示,与正常对照组比较,单独照射组小鼠睾丸生精小管萎缩明显,生精上皮出现大量空泡结构;与单独照射组比较,染料木素混悬液组小鼠睾丸生精上皮空泡占视野面积比例无差异,而包合物低、中、高剂量组小鼠睾丸生精上皮空泡占视野面积比例减小(P<0.05)。小鼠精子活力结果显示,与正常对照组比较,单独照射组小鼠精子活力下降(P<0.05);与单独照射组比较,染料木素混悬液组小鼠精子活力有升高的趋势,但差异没有统�Objective To prepare the inclusion complexes of genistein with hydroxypropyl-β-cyclodextrin,and explore whether the inclusion complexes can improve the protective effect of genistein against testicular ionizing radiation damage.Methods The inclusion complexes of genistein andβ-cyclodextrin with molar ratios of 1∶2,1∶2.5 and 1∶3 were prepared by ultrasonic method,and they were characterized by high-performance liquid chromatography,water solubility measurements,microscopic imaging and scanning electron microscope observation.Sixty male C57BL/6 mice were randomly divided into normal control group,irradiation group,low,me-dium and irradiation high dose inclusion complex groups(35,70 and 140 mg/kg inclusion complex by gavage,respectively)and genistein suspension group(70 mg/kg genistein by gavage),with 10 mice in each group.Another 30 male C57B/L mice were selected for fertility experiment and randomly divided into normal control group,irradiation group and inclusion complex group(140 mg/kg inclusion complex by gavage).Mice in irradiation group,low,medium and high dose inclusion complex groups and genistein suspension group were irradiated with 4 Gy X-ray.The mice in each treatment group were given the corresponding dose of drugs by gavage once a day for two weeks before irradiation and two weeks after irradiation.The pathological changes of testis and sperm motility were observed at 21 d after irradiation.From 36 d after irradiation,the male rats were continuously cohabited with normal female rats in each group in fertility experiment,and the conception rate and the litter size were recorded.Results When the molar ratio of genistein to hydroxypropylβ-cyclodextrin was 1∶3,the inclusion rate of the prepared clathrate was the highest(94.49%,92.87%and 91.63%for the three batches),the solubility was increased by 405 times,the inclusion complex and the physical mixture had obvious differences in structure and micro-morphology under microscope and scanning electron microscope,which indicated that the inclusion c

关 键 词：染料木素 羟丙基-Β-环糊精 包合物 电离辐射 睾丸 精子 

分 类 号：R965[医药卫生—药理学]