CN107308317B - 一种防治辐射损伤的中药组合物 - Google Patents
一种防治辐射损伤的中药组合物 Download PDFInfo
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Abstract
本发明一方面提供了一种防治辐射损伤的中药复方制剂归芪益元膏,包括有按重量份计的如下组分:黄芪25~35份、人参12~18份、当归12~18份、熟地12~18份、枸杞子12~18份、麦冬12~18份、五味子8~12份。另一方面,构建病证结合大鼠12C6+束辐射损伤模型,为辐射损伤领域的研究提供动物模型支撑。归芪益元膏能减轻12C6+束辐射造成的旁效应,其机制与改善氧化应激反应水平有关。
Description
技术领域
本发明涉及一种防治辐射损伤的中药复方制剂归芪益元膏,也涉及一种辐射损伤动物模型的构建方法,属于中药技术领域。
背景技术
重离子束(12C6+)是21世纪最理想的放疗射线,在治疗肿瘤方面有极好的发展前景。一方面,由于12C6+束在治疗靶区肿瘤时,对正常组织的辐射损伤不容忽视,因此开发药物防治12C6+束的辐射损伤意义重大。另一方面,令人遗憾的是,在辐射损伤的探索领域,缺乏病证结合动物模型的支撑阻碍了中医中药的防治研究。
发明内容
本发明一方面提供了一种防治辐射损伤的中药复方制剂归芪益元膏,另一方面,研究拟构建病证结合大鼠12C6+束辐射损伤模型,为今后辐射损伤领域的研究提供动物模型支撑。
本发明的第一个方面:
一种防治辐射损伤的中药组合物,包括有按重量份计的如下组分:黄芪25~35份、人参 12~18份、当归12~18份、熟地12~18份、枸杞子12~18份、麦冬12~18份、五味子8~12份。
在一个实施例中,黄芪30份、人参15份、当归15份、熟地15份、枸杞子15份、麦冬 15份、五味子10份。
本发明的第二个方面:
包含有上述中药组合物的中药制剂。
本发明的第三个方面:
中药组合物的制备方法,将各组分进行通过粉碎、压榨、研磨、过筛、渗漉、萃取、水提、醇提、酯提或者层析。
本发明的第四个方面:
大鼠12C6+束辐射损伤模型的构建方法,包括如下步骤:对Wistar大鼠在麻醉状态下接受12C6+束辐射肺部。
辐射强度是250MeV,辐射剂量是8Gy。
麻醉前12小时Wistar大鼠禁食。
本发明的第五个方面:
上述的中药组合物在用于制备12C6+束辐射损伤的治疗药物中的应用。
所述的12C6+束辐射损伤包括有哺乳动物的红细胞(RBC)、白细胞(WBC)、血红蛋白(HGB)、血小板(PLT)的降低。
所述的12C6+束辐射损伤包括有哺乳动物的脾脏指数和胸腺指数降低。
所述的12C6+束辐射损伤包括有骨髓细胞G2/M期阻滞、DNA合成能力阻滞、γH2AX蛋白表达量升高、53BP1蛋白表达量升高、mRNA表达量升高、Bax蛋白表达量升高或者PCNA 蛋白表达量升高。
药理作用:归芪益元膏是博士后导师李金田教授率领的课题组,在多年研究中药复方防治辐射损伤的过程中发明创制的,方由黄芪、人参、当归、熟地、枸杞子、麦冬、五味子组成。黄芪味甘性微温,归脾、肺经,人参味甘微苦性微温,归脾、肺经,二者大补元气,共为君药;当归味辛甘性温,归肝、心、脾经,补血活血,熟地味甘性微温,归肝、肾经,益真阴,滋肾水,二者共为臣药;枸杞子味甘性平,归肝、肾、肺经,滋补肝肾,为佐药;麦冬味甘微苦性微寒,归心、肺、胃经,润肺养阴,五味子味酸性温,归肺、肾、心经,上敛肺气、下滋肾阴,二药同伍,以达“金水相生”的效果,共为使药。该方中的人参、麦冬、五味子组成了生脉散,是益气生津的名方。上述诸药合用,共奏益气滋阴之效。归芪益元膏能减轻12C6+束辐射造成的旁效应,其机制与改善氧化应激反应水平有关。
20世纪60年代邝安堃教授首开先河发现过量肾上腺皮质激素可诱发小鼠呈现类似中医阳虚症状,证候动物模型的发展已走过了整整50年。笔者采用对疾病动物模型进行辨证建立病证结合动物模型。该病证结合动物模型具有疾病和证候的双重特征,为辐射损伤动物模型首次提供了证候物质基础。通过以方测证,进一步证实该模型的合理性,对这一领域的研究奠定了初步基础,为中医中药介入辐射损伤防治领域提供了可靠的动物模型支撑。
本发明的以上组成中,各味药的重量是以生药计算的,如果以克为单位,上述配方组成可制成一个疗程剂量的药物制剂,若日服2-4次,为20-40天的服用量,如制成制剂,则因制剂的大小不同可制成100-1000剂。所述100-1000剂是指单位剂量的制剂形式,如片剂100-1000片,胶囊剂100-1000粒,颗粒剂l00-1000份,口服液l00-l000ml,膏剂l00-l000份,丸剂10-1000丸等。
以上组成是按重量作为配比的,在生产时可按照相应比例增大或减少,如大规模生产可以以kg为单位,或以t(吨)为单位;小规模制剂也可以以g为单位。重量可以增大或者减小,但各组成之间的生药材重量配比的比例不变。
以上重量配比的比例是经过科学筛选得到的,对于特殊病人,如重症或轻症,肥胖或瘦小的病人,可以相应调整组成的量的配比,增加或减少不超过100%,药效基本不变。
本发明的中药组合物,是通过将上述配方组成的中药原料药材经过提取或其他方式加工,制成药物活性物质,随后,以该物质为原料,需要时加入药物可接受的载体,按照制剂学的常规技术制成的。所述活性物质可以通过分别提取中药原料得到,也可以通过共同提取中药原料药材得到,也可以通过其他方式待到,如:通过粉碎、压榨、研磨、过筛、渗漉、萃取、水提、醇提、酯提、层析等方法得到、这些活性物质可以是浸膏形式的物质,可以是干浸膏也可以是流浸膏,根据制剂的不同需要决定制成不同的浓度。
本发明的中药组合物,优选的是单位剂量的药物制剂形式,在制成药物制剂时可以制成任何可药用的剂型,这些剂型选自:片剂、胶囊剂、口服液、口含剂、颗粒剂、丸剂、散剂、膏剂、丹剂、优选的是口服制剂形式,最优选的是丸剂,片剂,胶囊剂,颗粒剂。
本发明的中药组合物,其药物活性物质是经过提取加工制得的,如可以用以下方法加工:
以上药物粉碎,用炼蜜制丸,
或
以上药物经过水煮,得到水提取物,浓缩成膏,以该清膏为原料,需要时加入药物可接受的载体,按照制剂学的常规技术制成。
本发明的中药组合物,根据需要可以加入一些药物可接受的载体,可以采用制剂学常规技术制备该药物制剂,如将药物活性物质与药物可接受的载体混合。所述药物可接受的的载体选自:蜂蜜、练蜜、甘露醇、山梨醇、山梨酸或钾盐、焦亚硫酸钠、亚硫酸氢钠、硫代硫酸钠、盐酸半胱氨酸、巯基乙酸、蛋氨酸、维生素A、维生素C、维主素E、维生素D、氮酮、EDTA二钠、EDTA钙钠,一价碱金属的碳酸盐、醋酸盐、磷酸盐或其水溶液、盐酸、醋酸、硫酸、磷酸、氨基酸、氯化钠、氯化钾、乳酸钠、木糖醇、麦芽糖、葡萄糖、果糖、右旋糖苷、甘氨酸、淀粉、蔗糖、乳糖、甘露糖醇、硅衍生物、纤维素及其衍生物、藻酸盐、明胶、聚乙烯吡咯烷酮、甘油、丙二醇、乙醇、土温60-80、司班-80、蜂蜡、羊毛脂、液体石蜡、十六醇、没食子酸酯类、琼、三乙醇胺、碱性氨基酸、尿素、尿囊素、碳酸钙、碳酸氢钙、表面活性剂、聚乙二醇、环糊精、B-环糊精、磷脂类材料、高岭土、滑石粉、硬脂酸钙、硬脂酸镁等。
本发明的中药制剂,在制成药剂时,单位剂量的药剂可含有本发明的药物活性物质 0.1~l000mg,其余为药学上可接受的载体。药学上可接受的载体以重量计可以是制剂总重量的0.01-99.9%。
本发明的药物制剂在使用时根据病人的情况确定用法用量。服用方法因病人的体质情况对症服用,如日服1-4次,每次1-4丸。
附图说明
图1 3组大鼠总路程比较其中,
图2 3组大鼠活动时间比较
图3 3组大鼠休息时间比较
图4 3组大鼠平均速度比较
图5 3组大鼠摄食量比较
图6 3组大鼠饮水量比较
图7 3组大鼠心率比较
图8 3组大鼠肛温比较
图9 3组大鼠排尿量比较
图10 3组大鼠体重比较
图11 3组大鼠血象比较
图12 3组大鼠脾脏指数、胸腺指数比较
图13归芪益元膏的制备工艺流程图
图14大鼠肺肾组织病理形态学改变(空白对照组(左肺))
图15大鼠肺肾组织病理形态学改变(单纯辐射组(左肺))
图16大鼠肺肾组织病理形态学改变(归芪益元膏组(左肺))
图17大鼠肺肾组织病理形态学改变(空白对照组(右肺))
图18大鼠肺肾组织病理形态学改变(单纯辐射组(右肺))
图19大鼠肺肾组织病理形态学改变(归芪益元膏组(右肺))
具体实施方式
实施例1
材料
1.动物健康雄性SPF级Wistar大鼠,体质量180~200g,鼠龄38~40周,30只,由甘肃中医药大学实验动物中心提供,许可证号码:SCXK(甘)2015-0002。饲养期间保持自由饮水和进食,饲养环境温度为(24±1)℃,湿度为(55±5)%,实验前适应性喂养1周。
2.药物和试剂归芪益元膏药物组成:黄芪30g、人参15g、当归15g、熟地15g、枸杞子15g、麦冬15g、五味子10g。方中原药材由甘肃省高校中藏药化学与质量研究省级重点实验室提供并质量鉴定。归芪益元膏水煎液自制,生药共计115g,先用凉水浸泡30min,用水量为生药量的8倍,武火煎沸后,文火煎30min,滤出药液;再加6倍量水煎沸后文火煎20min,滤出药液,合并2次煎液,浓缩至97.28mL,生药量为1.028g/mL。水合氯醛(批号:20160325):国药集团上海化学试剂有限公司。
3.仪器中国科学院近代物理研究所兰州重离子研究装置(HIRFL-CSR)。大鼠自发活动视频分析系统:DigBehv-L,上海吉量软件科技有限公司。多道生理信号采集处理系统:RM6240BD,成都仪器厂。天平:910324,Sartorius anglytic。肛温表。动物血球分析仪:HEMAVET950s,美国HEMAVET。
方法
1.病证结合模型制备30只Wistar大鼠,采用随机数字表法分为正常对照组、单纯辐射组、归芪益元膏组,Wistar大鼠在麻醉状态下接受250MeV12C6+束辐射右侧肺部,辐射剂量 8Gy,麻醉剂为10%水合氯醛(300mg/Kg体重)腹腔注射,麻醉前12小时大鼠禁食。正常对照组也同步采取麻醉措施,辐射时右侧肺部对准束流窗口,辐射剂量0Gy。
各组分别于12C6+束照射前,正常对照组及单纯辐射组给予0.9%氯化钠注射液,每次2mL,每天1次ig,连续7天;归芪益元膏组给予归芪益元膏水煎液10.28g/(kg·d),每次2mL,每天1次ig,连续7天。各组分别于12C6+束照射后,继续按原定方案灌胃7天,处死大鼠,检测相关指标。
本实验中动物处置方法符合动物伦理学标准。
2.病证结合动物模型的诊断标准中医辨证标准参考《中医虚证辨证参考标准》中气虚、阴虚证的标准。具体证候:神疲乏力,纳呆,心悸,午后潮热,口干多饮,尿少便结,舌红绛少苔,脉细数。西医诊断标准参照《放射病诊断标准及处理原则》拟定。具体症状:乏力,食欲减退,白细胞明显下降。
3.客观指标测定
3.1自发活动采用大鼠自发活动视频分析系统观察各组大鼠于照射后第1、3、7天的总路程、活动时间、休息时间、平均速度的变化。
3.2摄食量、饮水量、心率、肛温、排尿量、体重各组大鼠于照射后第1、3、7天早晨9时灌胃前,分别称量剩余食物量、剩余饮水量、排尿量、体重并作记录以观察摄食量、饮水量、排尿量、体重。各组大鼠于上述同样时间点用多道生理信号采集处理系统记录心率。各组大鼠于照射后第1、3、7天下午15时用肛温表测肛门温度并作记录。
3.3血象大鼠辐射7天后采样,取材前称重,股动脉取血,采用动物血球分析仪对血象进行检测。
3.4脾脏指数、胸腺指数各组大鼠处死后,立即取出脾脏和胸腺,计算脾脏指数及胸腺指数。
结果
1.3组大鼠自发活动变化见图1~4(注:与正常对照组比较,**P<0.01;与单纯辐射组比较,△△P<0.01)。单纯辐射组的总路程、活动时间、平均速度呈降低趋势,休息时间呈增加趋势,与正常对照组比较均有极显著差异(P<0.01),表明辐射使大鼠的自发活动趋向减弱。归芪益元膏组的总路程、活动时间、平均速度呈增高趋势,休息时间呈降低趋势,并且从辐射后第1天到第7天与单纯辐射组比较有极显著差异(P<0.01),表明归芪益元膏处理对辐射大鼠的自发活动有改善作用。
2.3组大鼠摄食量、饮水量、心率、肛温、排尿量、体重变化见图5~10(注:与正常对照组比较,**P<0.01;与单纯辐射组比较,△△P<0.01)。正常对照组摄食量、饮水量、体重呈逐渐增长趋势。单纯辐射组的摄食量、排尿量、体重呈下降趋势,饮水量、心率、肛温呈上升趋势,与正常对照组比较均有极显著差异(P<0.01),表明辐射可影响大鼠的摄食量、饮水量、心率、肛温、排尿量、体重。归芪益元膏组的摄食量、饮水量、心率、肛温、体重呈上升趋势,排尿量呈下降趋势,并且从辐射后第1天到第7天与单纯辐射组比较有极显著差异(P<0.01),表明归芪益元膏处理可明显改善辐射大鼠的上述症状及体征。
3.3组大鼠血象变化见图11(注:与正常对照组比较,**P<0.01;与单纯辐射组比较,△△P<0.01)。单纯辐射组的红细胞(RBC)、白细胞(WBC)、血红蛋白(HGB)、血小板(PLT) 降低,与正常对照组比较均有极显著差异(P<0.01),表明辐射改变了大鼠的血象。归芪益元膏组的RBC、WBC、HGB、PLT升高,与单纯辐射组比较有极显著差异(P<0.01),表明归芪益元膏处理对辐射大鼠血象有一定的保护作用。
4.3组大鼠脾脏指数、胸腺指数变化见图12(注:与正常对照组比较,**P<0.01;与单纯辐射组比较,△△P<0.01)。单纯辐射组的脾脏指数和胸腺指数降低,与正常对照组比较均有极显著差异(P<0.01),表明辐射改变了大鼠的脾脏指数和胸腺指数。归芪益元膏组的脾脏指数和胸腺指数升高,与单纯辐射组比较有极显著差异(P<0.01),表明归芪益元膏处理可明显减轻辐射对大鼠脾脏和胸腺的损伤,有一定的保护作用。
实施例2
1实验动物分组
SPF级健康雄性Wistar大鼠42只,体重(200±20)g,由甘肃中医药大学SPF级实验动物中心提供(合格证号SCXK(甘)2015-0002),查随机数字表将其分为空白对照组、单纯辐射组和辐照+药物组。饲养在甘肃中医药大学SPF级实验动物中心,SPF级实验动物设施使用证号为SYXK(甘)2015-0005。
2实验药品制备
方药组成:黄芪30g,当归、熟地、麦冬、人参、枸杞子各15g,五味子10g。方中原药材由本校甘肃省高校中藏药化学与质量控制实验室提供并质量鉴定。制备过程由甘肃中医药大学中药制药实验室完成。归芪益元膏按下述方法制备:取处方量药材,加12倍量水回流提取2次,每次6倍量水,每次回流1.5小时,合并提取液,沉降,300目筛过滤,减压浓缩至生药量1.5g/ml,作为药膏。分别以原药膏2wt‰的比例加入阿斯巴甜,3wt‰的比例加入苯甲酸钠,与原药膏混合均匀,溶解。取黄原胶(原药膏的4wt‰)和1,2-丙二醇按1:5的比例配成混悬液,加入上述药膏中,混合均匀后,用胶体磨循环研磨1分钟,收膏,灌装、灭菌,即得。流程如图13所示。
3实验动物灌胃
各组分别于12C6+束照射前,正常对照组及单纯辐射组给予0.9%氯化钠注射液,每次2mL,每天1次ig,连续7天;归芪益元膏组给予归芪益元膏10.28g/(kg·d),每次2mL,每天1次 ig,连续7天。
4实验动物照射
重离子照射在中国科学院近代物理研究所兰州重离子加速器研究装置(HeavyIon Research Facility in Lanzhou-Cooler Storage Ring,简称HIRFL-CSR)的浅层肿瘤治疗终端上进行,束流为12C6+离子束。坪区照射,能量为165MeV,LET为20keV/um,吸收剂量率为2Gy/min,用空气电离室监测剂量,单纯辐射组和辐照+药物组大鼠右肺部照射剂量为2Gy。
5实验动物处理
照射后分别于6h、12h、24h处死各组大鼠6只,取血,取左、右肺、左肾组织进行相关指标检测。
6指标检测方法
Q-PCR、Western-blot和免疫组化检测大鼠右肺、左肺、左肾组织中DNA损伤、细胞增殖及凋亡相关基因表达情况,硝酸还原酶法检测NO含量变化,HE染色观察大鼠左肺、右肺组织形态学变化。全自动动物血球分析仪检测大鼠外周血象变化。流式细胞仪检测骨髓细胞周期的变化。
7实验结果
7.1大鼠一般状况
辐射各组大鼠精神差,反应迟钝,活动减少,呼吸急促,体重减轻,皮毛褪色,但未出现死亡。解剖后辐射各组大鼠肺部淤血严重。辐照+中药组大鼠精神尚可,皮毛润泽,呼吸平稳,无死亡,肺部淤血减轻。
7.2各组大鼠肺肾病理形态学变化(图14-19所示)
空白对照组大鼠双肺组织结构清晰,无炎性细胞浸润,肺泡壁薄而光滑,无增厚,肺泡腔完整,腔内无渗出物,血管正常;在直接照射的右肺组织,单纯辐射6h、12h、24h组可见肺泡壁增厚,肺泡壁毛细血管充血,肺泡腔内出血,炎性细胞浸润。
在旁组织左肺中,单纯辐射6h、12h组大鼠肺泡壁毛细血管无充血、出血,肺泡壁无增厚,肺泡腔完整,腔内无渗出物。单纯辐射24h组,肺泡壁增厚,局灶可见炎性细胞浸润。
在直接照射的右肺,与单纯辐射组相比,归芪益元膏6h、12h、24h组大鼠肺泡壁无增厚,肺泡腔内无渗出物,肺泡壁毛细血管无充血、出血,有少量炎性细胞浸润。在旁组织左肺中,归芪益元膏各组大鼠肺泡壁无增厚,肺泡腔内无渗出物,未见炎性细胞浸润,肺泡壁毛细血管无充血、出血。
7.3各组大鼠骨髓细胞周期的变化(表2)
在辐射6h后,大鼠骨髓细胞周期未发生明显改变。在辐射后12h,G2/M期细胞率由4.36%变为7.18%,辐射后24h,G2/M期细胞率由7.18%变为9.27%,两个时间点均出现明显上扬,说明在右肺受辐射后,骨髓细胞出现了G2/M期阻滞。大鼠用药物干预后其右肺部再进行重离子辐射,在辐射后6h、12h、24h出现了G0/G1期细胞率的下降,S期细胞率的上扬,说明中药可以促进骨髓细胞从G0/G1期进入S期,促进S期DNA合成能力,保证细胞周期的正常进行。
注:*与空白组比较,P<0.05
7.4各组大鼠外周血白细胞、红细胞、血小板、血红蛋白结果(表3)
单纯辐射组大鼠外周血象WBC、RBC、PLT、HGB在照射后12h明显下降,与空白对照组相比,差异具有统计学意义(P<0.01);辐照+药物组明显升高,与单纯辐射组12h比较,差异具有统计学意义(P<0.01)。
与空白对照组相比*P<0.01,与单纯辐射组12h相比ΔP<0.01
7.5各组大鼠肺肾组织中γ-H2AX、53BP1蛋白及mRNA表达变化(表4-7)
单纯辐射组大鼠左右肺、左肾中γH2AX、53BP1蛋白及mRNA表达量在辐射后12h、24h 明显升高,与空白对照组相比,差异有统计学意义(P<0.05)。与同时间点单纯辐射组相比,辐照+药物组大鼠左右肺、左肾中γH2AX、53BP1蛋白及mRNA表达量在辐射后12h、24h 明显降低,差异有统计学意义(P<0.05)。
注:*与空白组比较,P<0.05;△与同时间点单纯辐射组比较,P<0.05
注:*与空白组比较,P<0.05;△与同时间点单纯辐射组比较,P<0.05
注:**与空白组比较,P<0.05;△△与同时间点单纯辐射组比较,P<0.05
注:*与空白组比较,P<0.05;△与同时间点单纯辐射组比较,P<0.05
7.6各组大鼠肺肾组织中Bax蛋白及mRNA表达变化(表8-9)
辐射后24h右肺、左肺、左肾组织中Bax mRNA及蛋白表达模型上调,与空白对照组相比,差异具有统计学意义(P<0.01);辐照+药物组明显下调,与单纯辐射组相比,差异具有统计学意义(P<0.01)。
与空白对照组相比,*P<0.01;与同时间点单纯辐射组相比,ΔP<0.01(平均灰度值越大,蛋白表达越低)
注:与空白对照组比较,*P<0.01;与同时间点单纯辐射组相比,ΔP<0.01
7.7各组大鼠肺肾组织中PCNA蛋白及mRNA表达变化(表10-11)
*与空白组比较,P<0.05;**与空白组比较,P<0.01△与模型组比较,P<0.05;△△与空白组比较,P <0.01
*与空白组比较,P<0.05;**与空白组比较,P<0.01△与模型组比较,P<0.05;△△与空白组比较,P <0.01
辐射后24h右肺、左肺、左肾组织中PCNAmRNA及蛋白表达模型上调,与空白对照组相比,差异具有统计学意义(P<0.05);辐照+药物组明显下调,与单纯辐射组相比,差异具有统计学意义(P<0.05)。
讨论
1.病证结合动物模型的造模依据
1.1模拟病因 重离子是指原子序数大于质子的正离子,如碳离子(12C6+)等。肿瘤重离子治疗是把12C6+注入同步加速器使之处于高能状态,加速到接近光速并在束流上予以控制,再引出来治疗照射肿瘤,可直接导致对周边正常组织的辐射损伤。在中医古籍中鲜有辐射损伤的相关记载。现代研究发现,当高能粒子作用于机体时,高能粒子的能量在短时间内以热的形式传递给机体,超出机体的承受能力,可中伤机体,形成类似火热温毒的致病证候。《素问·阴阳应象大论》云:“壮火之气衰,少火之气壮;壮火食气,气食少火;壮火散气,少火生气。”张景岳《类经》注:“火,天地之阳气也。天非此火,不能生物;人非此火,不能有生。故万物之生,皆由阳气。但阳和之火则生物,亢烈之火反害物,故火太过气反衰,火和平则气乃壮。”从中医理论角度分析,12C6+束乃六气之属,为火热之气,常则宜人,过则演变为六淫之属-壮火,耗伤气阴,出现气阴两虚证。
1.2模拟症状 按照病证结合动物模型的诊断标准,对照单纯辐射组大鼠的临床症状,我们可以推断辐射损伤模型大鼠的证候属性。12C6+束辐射大鼠右侧肺部以后,耗伤肺之气阴,继之出现全身气阴亏损,因此与正常对照组相比较,单纯辐射组大鼠神疲懒动,纳呆,心悸,午后潮热,口干多饮,尿少便结,舌红绛少苔。证明该模型的证候属性是气阴两虚证。
1.3客观指标 本实验结果表明,与正常对照组比较,单纯辐射组的自发活动(总路程、活动时间、平均速度)在照射12C6+束后的1~7天内趋向降低,自发活动(休息时间)呈增加趋势(P<0.01),表明辐射使大鼠的自发活动趋向减弱。正常对照组摄食量、饮水量、体重呈逐渐增长趋势。单纯辐射组的摄食量、排尿量、体重呈下降趋势,饮水量、心率、肛温呈上升趋势,与正常对照组比较均有极显著差异(P<0.01),表明辐射可影响大鼠的摄食量、饮水量、心率、肛温、排尿量、体重。符合气阴两虚证的证候表现。
血象反映了机体造血系统的机能状态,造血系统是对辐射损伤最敏感的系统之一,血象中红细胞(RBC)和白细胞(WBC)的计数变化是衡量辐射损伤的生化指标之一。本实验中,单纯辐射组的RBC和WBC降低,与正常对照组比较均有极显著差异(P<0.01),表明12C6+束辐射右侧肺部对大鼠骨髓造血系统有一定损伤。脾脏和胸腺是哺乳动物重要的免疫器官,同骨髓一样是免疫细胞形成、各种免疫因子产生的场所,共同构成机体的防御系统。脾脏和胸腺同样对辐射损伤最为敏感。本实验中12C6+束辐射导致单纯辐射组的脾脏指数和胸腺指数降低,与正常对照组比较均有极显著差异(P<0.01),表明辐射损伤了大鼠的免疫器官-脾脏和胸腺。符合西医诊断标准-《放射病诊断标准及处理原则》。
以上显示和描述了本发明的基本原理和主要特征和本发明的优点。本行业的技术人员应该了解,本发明不受上述实施例的限制,上述实施例和说明书中描述的只是说明本发明的原理,在不脱离本发明精神和范围的前提下,本发明还会有各种变化和改进,这些变化和改进都落入要求保护的本发明范围内,本发明要求保护范围由所附的权利要求书及其等效物界定。
Claims (7)
1.一种防治辐射损伤的中药组合物,其特征在于,是由按重量份计的如下组分所组成:黄芪25~35份、人参12~18份、当归12~18份、熟地12~18份、枸杞子12~18份、麦冬12~18份、五味子8~12份。
2.根据权利要求1所述的防治辐射损伤的中药组合物,其特征在于,组分是:黄芪30份、人参15份、当归15份、熟地15份、枸杞子15份、麦冬15份、五味子10份。
3.包括有权利要求1或2所述的中药组合物的制剂。
4.权利要求1或2所述的中药组合物在用于制备12C6+束辐射损伤的治疗药物中的应用。
5.根据权利要求4所述的应用,其特征在于,所述的12C6+束辐射损伤包括有哺乳动物的红细胞、白细胞、血红蛋白、血小板的降低。
6.根据权利要求4所述的应用,其特征在于,所述的12C6+束辐射损伤包括有哺乳动物的脾脏指数和胸腺指数降低。
7.根据权利要求4所述的应用,其特征在于,所述的12C6+束辐射损伤包括有骨髓细胞G2/M期阻滞、DNA合成能力阻滞、γH2AX蛋白表达量升高、53BP1蛋白表达量升高、mRNA表达量升高、Bax蛋白表达量升高或者PCNA蛋白表达量升高。
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