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WO2017177479A1 - 丁香醛在制备电离辐射致肠道损伤防护药物中的应用 - Google Patents

丁香醛在制备电离辐射致肠道损伤防护药物中的应用 Download PDF

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WO2017177479A1
WO2017177479A1 PCT/CN2016/080222 CN2016080222W WO2017177479A1 WO 2017177479 A1 WO2017177479 A1 WO 2017177479A1 CN 2016080222 W CN2016080222 W CN 2016080222W WO 2017177479 A1 WO2017177479 A1 WO 2017177479A1
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syringaldehyde
ionizing radiation
use according
intestinal
radiation
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PCT/CN2016/080222
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English (en)
French (fr)
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尚增甫
谷蒙蒙
周平坤
肖倍倍
李明
薛培君
卢双双
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苏州大学张家港工业技术研究院
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Publication of WO2017177479A1 publication Critical patent/WO2017177479A1/zh

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/11—Aldehydes

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  • the invention relates to the application of syringaldehyde, in particular to the application of syringaldehyde in the preparation of a protective agent for intestinal damage caused by ionizing radiation.
  • Intestinal damage caused by ionizing radiation is one of the important causes of early death in patients with acute radiation sickness.
  • patients with malignant tumors are another special group exposed to ionizing radiation.
  • Radiation therapy is an important treatment for malignant tumors. It is reported that more than 70% of patients with malignant tumors need radiation therapy, and intestinal damage is tumor radiation in the abdomen and pelvis. Treatment of common side effects, resulting in greatly reduced patient quality of life, and even forced to terminate treatment due to very serious radiation damage. It can be seen that the development of protective drugs for intestinal damage caused by ionizing radiation is crucial for the construction of nuclear safety protection system and clinical adjuvant therapy for tumors.
  • Chinese patent CN200610130717.3 discloses the use of 3,5-dimethoxy-4-hydroxybenzaldehyde (the same substance as syringaldehyde) to protect cell damage in vitro by protecting alpha particle radiation;
  • Chinese patent CN201510122843.3 discloses A new use of syringaldehyde in the preparation of radiocarcinogenic protective drugs. Neither of these patents relates to the use of syringaldehyde in the preparation of protective agents for intestinal damage caused by ionizing radiation.
  • the present invention provides an application of syringaldehyde with small toxic and side effects and remarkable curative effect in preparing a protective agent for intestinal damage caused by ionizing radiation.
  • the medicament contains one or more pharmaceutically acceptable carriers.
  • the pharmaceutically acceptable carrier is selected from the group consisting of a diluent, an excipient, a filler, a binder, a wetting agent, a disintegrant, an absorption enhancer, a surfactant, an adsorption carrier, and a lubricant.
  • a diluent an excipient
  • a filler a filler
  • a binder a wetting agent
  • a disintegrant e.g., a sulfate, a filler, a binder, a wetting agent, a disintegrant, an absorption enhancer, a surfactant, an adsorption carrier, and a lubricant.
  • the pharmaceutical dosage form is an injection, a suspension, a powder, a tablet or a granule.
  • the drug is administered by intragastric administration.
  • the drug contains sodium carboxymethylcellulose as a diluent.
  • the drug is prepared by dissolving syringaldehyde in an aqueous solution of sodium carboxymethylcellulose.
  • the sodium carboxymethylcellulose has a mass concentration of 0.5 to 1%, wherein the syringaldehyde has a mass concentration of 5 to 10 mg/ml.
  • the drug is administered at a dose of 100-200 mg/kg by weight and administered 1 hour before ionizing radiation.
  • the intestinal damage caused by the ionizing radiation is intestinal damage caused by alpha rays, beta rays, gamma rays or X-ray radiation, or intestinal damage caused by radiation of radiation substances.
  • the present invention has at least the following advantages:
  • the invention provides the protective agent for intestinal damage caused by ionizing radiation with syringaldehyde as an active ingredient, and has the following advantages: (1) small side effects, no obvious adverse reaction in mice treated at a concentration of 100 mg/kg body weight; concentration of 40 ⁇ mol/L drug Treating rat intestinal epithelial cells, The cells were in good condition and no adverse reactions were identified. (2) The curative effect was significant. The dose of 100 mg/kg body weight 1 hour before irradiation could significantly increase the survival time of mice after 10 Gy irradiation; protect the mice receiving ionizing radiation.
  • the intestinal villus is structurally intact, promotes the proliferation of mouse intestinal crypt cells, and greatly reduces the apoptosis of mouse crypt cells induced by ionizing radiation; (3) Gene chip results show that syringaldehyde can regulate ionization at a concentration of 100 mg/Kg After irradiation, the mouse intestinal nervous system is balanced; (4) The main route of administration is oral, and the drug is convenient and safe. It is applicable to patients with acute radiation sickness, nuclear workers, officers and soldiers, astronauts, radiotherapy patients, etc. The medicine can be used before treatment or during tasks and work. All of the above properties show the uniqueness of syringaldehyde in protecting intestinal damage caused by ionizing radiation, and it has broad application prospects in the medical field in China.
  • 1 is a comparison chart of survival curves of a control group and a pre-irradiation syringaldehyde-administered group after irradiation with 10 Gy X-rays;
  • Figure 2 is a schematic view showing the toxic and side effects of syringaldehyde on rat intestinal epithelial cells
  • Figure 3 is a schematic view showing the structure of intestinal villi and crypts of mice after syringaldehyde protection 9Gy cobalt-60 ⁇ ray irradiation;
  • Figure 4 is a schematic diagram showing the proliferation of intestinal crypts in mice after syringaldehyde maintenance of 9 Gy cobalt-60 ⁇ -ray irradiation;
  • Figure 5 is a schematic view showing the inhibition of apoptosis of mouse intestinal crypt cells by syringaldehyde after 9Gy cobalt-60 ⁇ ray irradiation;
  • Figure 6 is a schematic diagram showing the effect of syringaldehyde on the expression of intestinal mRNA in mice after irradiation by the gene chip of the present invention.
  • mice 6-8 weeks old C57BL/6 mice, male and female (body weight 25 ⁇ 2g), were randomly divided into two groups: irradiation group (10Gy) 8 and pre-irdation syringaldehyde
  • the drug-administered group (10Gy + syringaldehyde) was used for 8 times; the mice were subjected to a single uniform irradiation with an X-ray irradiator, and the absorbed dose of the mice was 10 Gy.
  • the syringaldehyde was dissolved in a 0.5% aqueous solution of sodium carboxymethylcellulose, wherein the concentration of syringaldehyde was 5 mg/ml, and the mice in the syringaldehyde-administered group were intragastrically administered before irradiation (dose by weight: 100 mg/kg) After 1 h, the irradiated mice were given an equal volume of a 0.5% aqueous sodium carboxymethylcellulose solution. The effects of syringaldehyde on the general condition and physical signs of irradiated mice were investigated. The mice in the irradiated group showed a significant decrease in activity 1 day after irradiation, and the diet was significantly decreased.
  • mice in the syringaldehyde-administered group were irradiated after irradiation.
  • the degree was significantly better than the irradiation control group.
  • the survival days of the mice were analyzed.
  • syringaldehyde was effective in prolonging the survival time of the mice after irradiation with high dose (10 Gy) X-rays. Therefore, syringaldehyde can improve the signs of irradiated mice and prolong the survival time of irradiated mice.
  • the current in vitro study of intestinal damage is recognized as a model of rat intestinal epithelial cells IEC-6.
  • the syringaldehyde was dissolved in dimethyl sulfoxide, the mother liquor concentration was 40 mmol/L, and the syringaldehyde solution having a concentration of 5, 10, 20, 40 ⁇ mol/L was prepared by stepwise dilution, and the diluted solution was used for culturing cells. DMEM medium.
  • the control group was treated with dimethyl sulfoxide in an equal volume of 40 ⁇ mol/L syringaldehyde solution.
  • IEC-6 cells were seeded in 96-well plates, and the above-mentioned different concentrations of syringaldehyde solution and dimethyl sulfoxide were added to the cells in the logarithmic growth phase. After 72 hours, CCK8 was used (purchased from Biyuntian Biotechnology Co., Ltd., operation). The method follows the instructions) to detect cell growth. As a result, as shown in Fig. 2, 40 ⁇ mol/L syringaldehyde still did not significantly change the proliferation rate of IEC-6 cells, and there was no morphological change visible to the naked eye under the microscope.
  • mice 6-8 weeks old C57BL/6 mice, male and female (body weight 25 ⁇ 2g), were randomly divided into four groups: 6 groups without irradiation, 6 groups in normal feeding, 6 groups in irradiation group, and syringaldehyde before irradiation.
  • the mice were subjected to a single uniform irradiation with a cobalt-60 ⁇ -ray source, and the absorbed dose of the mice was 9 Gy.
  • the syringaldehyde was dissolved in a 1% by mass aqueous solution of sodium carboxymethylcellulose, wherein the concentration of syringaldehyde was 10 mg/ml, and the mice in the syringaldehyde-administered group were intragastrically administered before irradiation (dose by weight: 100 mg/kg) Irradiation was performed 1 hour later; mice in the blank group and the irradiated group were given an equal volume of 0.5% aqueous sodium carboxymethylcellulose solution; the flagellin was dissolved in phosphate buffer, and the positive control flagellin administration group was irradiated before irradiation. Dosing 1 hour before irradiation, intraperitoneal injection, dose: 4 micrograms per mouse.
  • mice were sacrificed 3.5 days after irradiation, and the small intestine tissues were taken, fixed, embedded in wax blocks, and sectioned for HE staining.
  • ionizing radiation significantly caused the small intestine villi to break and fall off in mice;
  • the positive control flagellin administration group (irradiation + CBLB502) before irradiation significantly improved the intestinal structure of the mice after irradiation, and the villous shedding decreased.
  • the effect of the syringaldehyde administration group (irradiation + syringaldehyde) before irradiation was more obvious.
  • the intestinal structure was similar to the blank group, and the villi were neat and intact.
  • the intestinal crypt of the mouse usually increases in stress.
  • the intestinal crypt structure of the above groups of mice found that syringaldehyde can further promote the intestinal tract.
  • the crypt was enlarged, and the effect was better than that of the positive control flagellin administration group before irradiation.
  • Ki-67 is one of the markers of cell proliferation. From Fig. 4(A), we found that the intestinal crypts of the normal-fed blank group were positive for Ki-67, indicating that the crypt cells have sustained proliferation ability, as shown in Fig. 4(B) and Fig. 4(C). ) As shown, the number of Ki-67 positive crypts in the intestine of the irradiated mice at 3.5 days after irradiation alone was significantly decreased, and the ratio of Ki-67 positive cells in each crypt was also significantly decreased.
  • Pre-irradiation syringaldehyde administration group irradiation + syringaldehyde
  • pre-irradiation positive control flagellin administration group irradiation + CBLB502 mice intestinal crypt Ki-67 positive rate and average Ki-67 positive cells per crypt The number was greatly restored, and the effect of the syringaldehyde administration group before irradiation was significantly better than that of the positive control flagellin administration group before irradiation.
  • syringaldehyde protects the intestinal structure and function of mice after ionizing radiation.
  • mice In order to further analyze the protective effect of syringaldehyde on the intestinal tract of mice after ionizing radiation, we treated the mice according to the method of the implementation of three (1), collected the intestinal tissue, and then frozen with liquid nitrogen to extract RNA, the first strand of cDNA and the first Two-strand synthesis, fluorescently labeled cRNA synthesis, cRNA purification, cRNA concentration determination, cRNA sample fragmentation and chip hybridization, chip washing, and chip scanning. Scanning in an Agilent scanner with a resolution of 5 ⁇ m, the scanner automatically scans once with 100% and 10% PMT, and the results are automatically combined by Agilent software twice. The results of the Go process cluster analysis showed that (Fig.
  • syringaldehyde can regulate the balance of intestinal neuroendocrine system in mice after ionizing radiation, in which olfactory receptor activity and G protein coupled receptor activity signals G-protein coupled receptor activity is most evident in related gene changes in odorant binding associated with gas binding ( Figure 6), where Go:0001227 and Go:0001162 For unknown functional proteins.
  • Figure 6 olfactory receptor activity and G protein coupled receptor activity signals G-protein coupled receptor activity is most evident in related gene changes in odorant binding associated with gas binding
  • Go:0001227 and Go:0001162 For unknown functional proteins.
  • This example uses a omics method to discover the possible mechanism of syringaldehyde to protect the intestinal tract of mice after ionizing radiation.

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Abstract

本发明提供了丁香醛在制备电离辐射致肠道损伤防护药物中的应用、药剂形式和给药方式。本发明所提供的以丁香醛为活性成分的电离辐射致肠道损伤防护药物具有毒副作用小、疗效显著、用药方便安全等优势，对于急性放射病患者、涉核从业人员、官兵、宇航员、放疗病人等不同人员均适用，在治疗前或执行任务、工作中均可用药。上述性能均显示出丁香醛在防护电离辐射致肠损伤中的独特之处，在我国医学领域具有广阔的应用前景。

Description

丁香醛在制备电离辐射致肠道损伤防护药物中的应用 技术领域
本发明涉及一种丁香醛的应用，尤其涉及丁香醛在制备电离辐射致肠道损伤防护药物中的应用。
背景技术
随着我国核能的广泛开发、利用和涉核医学的飞速发展，人们暴露于电离辐射下的机会日益增多。2011年的福岛核电站事故和近期的朝核危机再次提醒我们核威胁仍然存在。
由于小肠上皮细胞更新极快，因此小肠对电离辐射非常敏感，是电离辐射最为重要的靶器官，电离辐射导致的肠损伤是急性放射病患者早期死亡的重要原因之一。另外，恶性肿瘤患者是接触电离辐射的又一特殊人群，放射治疗是针对恶性肿瘤的重要治疗手段，据报道，70％以上的恶性肿瘤患者需要经过放射治疗，肠损伤是腹部和骨盆内肿瘤放射治疗常见的副作用，导致病人生存质量大大降低，甚至出现由于放射损伤非常严重而被迫终止治疗。由此可见，电离辐射致肠损伤防护药物开发，对于在核安全保障体系构建和肿瘤临床辅助治疗中至关重要。
中国专利CN200610130717.3公开了3,5-二甲氧基-4-羟基苯甲醛(与丁香醛为同一物质)在防护α粒子射线对体外培养细胞损伤中的应用；中国专利CN201510122843.3公开了丁香醛在制备放射致癌防护药物中的新用途。此两项专利中均未涉及丁香醛在制备电离辐射致肠道损伤防护药物中的应用。
目前对于电离辐射致肠道损伤防护药物研究多处于临床前阶段，虽然部分药物有保护作用，但是存在显著缺点，主要包括：作用浓度高、活性偏低和存在明显的毒副作用，从而限制了临床应用，寻找无毒或低毒、高效的电离辐射致肠道损伤防护药物一直是医药界的追求 热点。
有鉴于上述的缺陷，本设计人，积极加以研究创新，以期创设一种丁香醛在制备电离辐射致肠道损伤防护药物中的应用，使其更具有产业上的利用价值。
发明内容
为解决上述问题，本发明提供了毒副作用小、疗效显著的丁香醛在制备电离辐射致肠道损伤防护药物中的应用。
进一步的，所述药物含有一种或多种药学上可接受的载体。
更进一步的，所述药学上可接受的载体选自稀释剂、赋形剂、填充剂、粘合剂、湿润剂、崩解剂、吸收促进剂、表面活性剂、吸附载体和润滑剂中的一种或几种。
进一步的，所述药物的剂型为注射剂、悬浮剂、粉剂、片剂或颗粒剂。
进一步的，所述药物经由灌胃给药。
更进一步的，所述药物含有羧甲基纤维素钠作为稀释剂。
更进一步的，所述药物由丁香醛溶解于羧甲基纤维素钠水溶液制得。
更进一步的，所述羧甲基纤维素钠的质量浓度为0.5-1％，其中所述丁香醛质量浓度为5-10mg/ml。
进一步的，所述药物的给药剂量按体重为100-200mg/kg，且在电离辐射前1小时给药。
进一步的，所述电离辐射致肠损伤为α射线、β射线、γ射线或X射线辐射导致的肠损伤，或放射线物质辐射导致的肠损伤。
借由上述方案，本发明至少具有以下优点：
本发明所提供的以丁香醛为活性成分的电离辐射致肠道损伤防护药物具有以下优点：(1)毒副作用小，100mg/kg体重浓度下处理小鼠无明显不良反应；40μmol/L药物浓度处理大鼠小肠上皮细胞， 细胞状态良好，无可辨识不良反应；(2)疗效显著，照射前1小时以100mg/kg体重浓度的剂量给药，能够显著调高10Gy射线照射后小鼠存活时间；保护接受电离辐射小鼠肠道绒毛结构完整，促进小鼠肠道隐窝细胞增殖，大幅度减少电离辐射致小鼠肠道隐窝细胞凋亡；(3)基因芯片结果显示100mg/Kg体重浓度的丁香醛能调控电离辐射后小鼠肠道神经免疫系统平衡；(4)主要给药途径为口服，用药方便、安全，对于急性放射病患者、涉核从业人员、官兵、宇航员、放疗病人等不同人员均适用，在治疗前或执行任务、工作中均可用药。上述性能均显示出丁香醛在防护电离辐射致肠损伤中的独特之处，在我国医学领域具有广阔的应用前景。
上述说明仅是本发明技术方案的概述，为了能够更清楚了解本发明的技术手段，并可依照说明书的内容予以实施，以下以本发明的较佳实施例并配合附图详细说明如后。
附图说明
图1为本发明10Gy X射线照射后照射对照组和照射前丁香醛给药组小鼠存活曲线对比图；
图2为本发明丁香醛对大鼠小肠上皮细胞无明显毒副作用示意图；
图3为本发明丁香醛保护9Gy钴-60γ射线照射后小鼠肠道绒毛和隐窝结构示意图；
图4为本发明丁香醛维持9Gy钴-60γ射线照射后小鼠肠道隐窝增殖示意图；
图5为本发明丁香醛抑制9Gy钴-60γ射线照射后小鼠肠道隐窝细胞凋亡示意图；
图6为本发明基因芯片分析丁香醛对照射后小鼠肠道mRNA表达的影响示意图。
具体实施方式
下面结合附图和实施例，对本发明的具体实施方式作进一步详细描述。以下实施例用于说明本发明，但不用来限制本发明的范围。
实施例一
首先建立辐射致肠道损伤小鼠模型，选用6-8周龄C57BL/6小鼠，雌雄各半(体重25±2g)，随机分两组：照射组(10Gy)8只和照射前丁香醛给药组(10Gy+丁香醛)8只；用X射线照射机对小鼠进行全身单次均匀照射，小鼠吸收剂量为10Gy。将丁香醛溶解于质量浓度为0.5％羧甲基纤维素钠水溶液，其中丁香醛的浓度为5mg/ml，照射前丁香醛给药组小鼠灌胃给药(剂量按体重：100mg/kg)1h后进行照射，照射组小鼠给予同等体积、质量浓度为0.5％羧甲基纤维素钠水溶液。考察丁香醛对照射小鼠一般情况和体征指标的影响，照射组小鼠在照射后1天即出现活动度显著下降，饮食量显著降低，而照射前丁香醛给药组在照射后小鼠活动度显著优于照射对照组。对小鼠存活天数进行分析，如附图1所示，丁香醛可有效延长照射高剂量(10Gy)X射线照射后小鼠存活时间。因此，丁香醛可以改善受照小鼠的体征、延长受照小鼠存活时间。
实施例二
选用目前体外研究肠损伤较为公认的大鼠肠道上皮细胞IEC-6为模型。将丁香醛溶解于二甲基亚砜中，母液浓度为40mmol/L，采用逐级稀释的方法配制使用浓度分别为5、10、20、40μmol/L的丁香醛溶液，稀释液为培养细胞用的DMEM培养液。对照组用等体积于40μmol/L丁香醛溶液的二甲基亚砜处理。IEC-6细胞接种于96孔板，在细胞处于对数生长期时分别加入上述不同浓度丁香醛溶液和二甲基亚砜，处理72小时后采用CCK8(购自于碧云天生物技术公司，操作方法遵循说明书)检测细胞生长情况。结果如附图2所示，40μmol/L丁香醛仍然未明显改变IEC-6细胞增殖速度，显微镜下观察形态也没有肉眼可见的形态改变。
实施例三
(1)首先建立钴-60γ射线致小鼠肠道损伤模型。选用6-8周龄C57BL/6小鼠，雌雄各半(体重25±2g)，随机分四组：未经照射处理、正常饲养的空白组6只、照射组6只、照射前丁香醛给药组(照射+丁香醛)6只、照射前阳性对照鞭毛蛋白给药组(照射+CBLB502)6只。用钴-60γ射线源对小鼠进行全身单次均匀照射，小鼠吸收剂量为9Gy。丁香醛溶解于质量浓度为1％的羧甲基纤维素钠水溶液，其中丁香醛的浓度为10mg/ml，照射前丁香醛给药组小鼠灌胃给药(剂量按体重：100mg/kg)后1小时进行照射；空白组和照射组小鼠给予同等体积、质量浓度为0.5％羧甲基纤维素钠水溶液；鞭毛蛋白溶解于磷酸盐缓冲液中，照射前阳性对照鞭毛蛋白给药组在照射前1小时给药，腹腔注射，剂量：平均每只小鼠4微克。
照射后3.5天处死小鼠，取小肠组织，固定、蜡块包埋，切片后进行HE染色。如附图3(A)所示，电离辐射明显导致小鼠小肠绒毛断裂、脱落；照射前阳性对照鞭毛蛋白给药组(照射+CBLB502)明显改善受照射后小鼠肠道结构，绒毛脱落减少；照射前丁香醛给药组(照射+丁香醛)效果更为明显，肠道结构与空白组类似，绒毛整齐、完整。
对绒毛长度进行定量分析，如附图3(B)所示，发现丁香醛可显著维持接受电离辐射小鼠小肠绒毛长度。
如附图3(C)所示，在9Gy射线照射后，通常小鼠肠道隐窝出现应激性增大，我们观察上述几组小鼠肠道隐窝结构发现丁香醛可进一步促进肠道隐窝增大，效果优于照射前阳性对照鞭毛蛋白给药组。
(2)按照(1)中所述处理方式收集小鼠肠道组织，切片后用抗Ki-67抗体进行免疫组化染色，Ki-67是细胞增殖的标志分子之一。从附图4(A)中，我们发现正常饲养的空白组小鼠肠道隐窝呈Ki-67阳性，表明隐窝细胞具有持续增殖能力，如附图4(B)和附图4(C) 所示，单纯接受照射后3.5天的照射组小鼠肠道Ki-67阳性隐窝数显著降低，每个隐窝中的Ki-67阳性细胞比率也显著下降。照射前丁香醛给药组(照射+丁香醛)和照射前阳性对照鞭毛蛋白给药组(照射+CBLB502)小鼠肠道隐窝Ki-67阳性率和平均每个隐窝Ki-67阳性细胞数得到大幅度恢复，其中照射前丁香醛给药组效果明显优于照射前阳性对照鞭毛蛋白给药组。
(3)电离辐射将导致肠道隐窝细胞发生凋亡，破坏肠道结构的再生能力，所以进一步分析检测丁香醛抗电离辐射诱发小鼠肠道隐窝细胞凋亡能力。由于细胞凋亡为早期生物学事件，因此我们依据(1)中的处理方法照射小鼠后6小时即处死小鼠，收集肠道组织，固定后用TUNEL凋亡检测试剂盒(罗氏公司)检测小鼠肠道隐窝细胞凋亡，对其凋亡比率进行定量分析发现，如附图5所示，丁香醛可以显著抑制电离辐射诱发的小鼠肠道隐窝细胞凋亡，抑制效果与鞭毛蛋白效果相当。
综上所述，丁香醛保护受电离辐射后小鼠肠道结构、功能。
实施例四
为了进一步分析丁香醛对电离辐射后小鼠肠道的保护作用，我们按照实施三(1)中的方法处理小鼠，收取肠道组织后用液氮冰冻，提取RNA，cDNA第一链和第二链合成，荧光标记cRNA合成，cRNA纯化，cRNA浓度测定，cRNA样品片段化和芯片杂交，芯片洗涤，芯片扫描。Agilent扫描仪中扫描，分辨率为5μm，扫描仪自动以100％和10％PMT各扫描一次，两次结果Agilent软件可自动合并。对所得结果进程Go聚类分析显示(附图6)丁香醛能够调控电离辐射后小鼠肠道神经内分泌系统平衡，其中嗅觉受体活性通路(olfactory receptor activity)、G蛋白偶联受体活性信号通路(G-protein coupled receptor activity)和气体结合相关联的信号通路(odorant binding)中相关基因改变最为明显(附图6)，其中Go：0001227和Go：0001162 为未知功能蛋白。目前有工作表明神经内分泌系统对于调控肠道功能非常关键，此实施例用组学的方法发现了丁香醛保护电离辐射后小鼠肠道的可能机制。
以上所述仅是本发明的优选实施方式，并不用于限制本发明，应当指出，对于本技术领域的普通技术人员来说，在不脱离本发明技术原理的前提下，还可以做出若干改进和变型，这些改进和变型也应视为本发明的保护范围。

Claims (10)

  1. 丁香醛在制备电离辐射致肠损伤防护药物中的应用。
  2. 根据权利要求1所述的应用，其特征在于：所述药物含有一种或多种药学上可接受的载体。
  3. 根据权利要求2所述的应用，其特征在于：所述药学上可接受的载体选自稀释剂、赋形剂、填充剂、粘合剂、湿润剂、崩解剂、吸收促进剂、表面活性剂、吸附载体和润滑剂中的一种或几种。
  4. 根据权利要求1-3中任一项所述的应用，其特征在于：所述药物的剂型为注射剂、悬浮剂、粉剂、片剂或颗粒剂。
  5. 根据权利要求1-3中任一项所述的应用，其特征在于：所述药物经由灌胃给药。
  6. 根据权利要求5所述的应用，其特征在于：所述药物含有羧甲基纤维素钠作为稀释剂。
  7. 根据权利要求6所述的应用，其特征在于：所述药物由丁香醛溶解于羧甲基纤维素钠水溶液制得。
  8. 根据权利要求7所述的应用，其特征在于：所述羧甲基纤维素钠的质量浓度为0.5-1％，其中所述丁香醛质量浓度为5-10mg/ml。
  9. 根据权利要求1或6所述的应用，其特征在于：所述药物的给药剂量为100-200mg/kg，且在电离辐射前1小时给药。
  10. 根据权利要求1所述的应用，其特征在于：所述电离辐射致肠损伤为α射线、β射线、γ射线或X射线辐射导致的肠损伤，或放射线物质辐射导致的肠损伤。
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Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
CHEN, QIANQIAN: "The Protective Effect of Vanillin Derivative VND3207 on Alpha particle Radiation", CHINA MASTER'S THESES FULL-TEXT DATABASE, MEDICINE & HYGIENE, 15 December 2010 (2010-12-15) *
GAO, FU ET AL.: "The Protective Effect of Procyanidine Pre-processing on in-vitro Human Cell Radiation Injury", ACADEMIC JOURNAL OF SECOND MILITARY MEDICAL UNIVERSITY, vol. 30, no. 6, 30 June 2009 (2009-06-30) *

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