姜辣素对不同剂量~(60)Co-γ射线辐射损伤小鼠治疗作用的研究
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摘要
目前,辐射已成为继水、大气、噪音污染之后的第四大污染。电离辐射作用于机体后,通过物理、化学和生物学的复杂机理,破坏DNA、蛋白质等大分子物质,进而造成各细胞、组织、器官以至整个机体功能、形态的损伤和变化,引起受照射者急、慢性辐射损伤甚至癌变。造血系统对电离辐射最为敏感,2 Gy照射即可造成小鼠造血系统损伤。
现阶段临床应用的抗辐射药物虽然疗效明显,但存在用药量大、毒副作用强等缺点。近年来辐射防治剂的研究热点逐渐转向抗辐射天然药物及功能食品的研究。生姜作为一种重要的中草药和日常饮食调味剂,具有镇静止吐,抑菌抗炎,降血糖、血脂和抗动脉硬化,抗氧化和清除自由基,抗肿瘤和增强免疫等功效。本研究将在已有的生姜辐射防护研究的基础上,进一步研究生姜提取物——姜辣素对不同剂量电离辐射(60~Co-γ射线)引起的造血系统和抗氧化系统损伤的治疗作用。
本研究选用60只健康雌性昆明小白鼠(6～8周龄,体重25～30 g),随机分为10组,每组6只,1组为对照组、2组为给药组,3-6组为照射组、7-10组为照射给药组。小鼠适应饲养一周后,3-10组小鼠进行照射,照射当天记为0天。3-6组分别接受1、3、5、7 Gy 60Co-γ射线照射,剂量率0.8 Gy/min,单次全身均匀照射。相同方法照射7-10组小鼠,并于照后30-60 min内灌胃姜辣素(800 mg/kg B.W.),总体积0.5 mL,连续5天(1次/天),3-6组小鼠灌胃同体积的蒸馏水。实验第6天颈椎脱臼处死小鼠,取血液、肝脏、脾脏、两侧股骨,以测定血常规、脏器指数、骨髓中DNA含量、骨髓嗜多染红细胞微核数目以及肝脏中SOD活性、T-AOC和MDA含量。本研究所得结果如下：
1.与对照组相比,给药组小鼠的脏器指数、DNA系数、肝脏中SOD活性和T-AOC能力均有不同程度的升高,外周血中红细胞、白细胞、淋巴细胞等血细胞含量有所升高,骨髓嗜多染红细胞中微核数目、肝脏MDA水平显著降低(p<0.05)。
2.60Co-γ射线照射后,小鼠肝脏指数的变化不大；与肝脏相比,脾脏对射线比较敏感,1 Gyγ射线即可引起脾脏指数显著低于对照组(p<0.01)。姜辣素可以提高小鼠脏器指数,尤其对3和5 Gy照射后脾脏指数降低能起到治疗效果(p<0.01)。
3.随着照射剂量的增大,照射组小鼠外周血中红细胞总数、血红蛋白含量、红细胞比积、白细胞总数、淋巴细胞比例逐渐降低。各剂量照射给药组小鼠血液中RBC、HGB、HCT、WBC、LYM含量均高于同剂量照射组,其中7 Gy照射给药组红细胞总数、血红蛋白含量、红细胞比积显著高于7 Gy照射组(p<0.05)；1 Gy照射给药组小鼠白细胞总数显著高于1 Gy照射组(p<0.05)。
4.不同剂量射线可不同程度地降低小鼠肝脏SOD酶活性和T-AOC能力,提高MDA含量。与对照组相比,5、7 Gy剂量照射组肝脏SOD酶活性显著降低(p<0.01),T-AOC能力也有所降低。各照射给药组小鼠肝脏SOD酶活性相比同剂量照射组SOD酶活性均有所升高,其中3 Gy照射给药组肝脏SOD酶活性显著高于3Gy照射组(p<0.05)；并且,3 Gy照射给药组T-AOC能力极显著高于3 Gy照射组(p<0.01),5 Gy照射给药组小鼠肝脏T-AOC能力显著高于5 Gy照射组(p<0.05)；1、3、5 Gy照射组小鼠肝脏MDA含量显著高于对照组(p 5.5和7 Gy照射组骨髓DNA系数显著低于对照组(p<0.01),5 Gy照射给药组骨髓DNA系数显著高于5 Gy照射组(p<0.01)；与对照组相比,1、3、5 Gy照射组微核数目显著升高(p<0.01),灌胃姜辣素后,照射给药组小鼠骨髓微核数目相比同剂量照射组显著降低(p<0.O 1)。
综上所述,姜辣素对不同剂量Y射线引起的造血系统和抗氧化系统辐射损伤有一定的治疗作用,尤其对3和5 Gy射线损伤小鼠的治疗效果较好。一方面,姜辣素增强了机体抗氧化能力,减少了射线对机体的损伤；另一方面,姜辣素提高了外周血中各种血细胞的数量,可维持机体正常功能代谢,减少各种放射病的发生；再者,姜辣素能提高骨髓DNA系数,减少微核数目,说明姜辣素可以阻止射线对遗传物质的损伤,促进DNA合成和修复,为机体其他器官系统的辐射后修复打下基础。
Radiation has been one heavy contamination around our everyday life. It can hurt cells, tissues and organs, even the whole body's function and metabolism through physical, chemical and biological mechanisms, which can bring acute and chronic radiation sickness. The hematopoietic system is the most sensitive to radiation. As one important Chinese medicine and flavoring, Ginger rhizome (ZOE) has been reported for its diminishing inflammation, treating vomit, antioxidation, antitumor, improving immunity and radical scavenging abilities. The therapetic effect of gingerol on radiated mice is further studied in this research.
6 to 8 weeks old Kunming mice weighing 25～30 g were selected from an inbred colony maintained under controlled conditions of temperature (23±2℃), humidity (50±5%) and light (14 and 10 hours of light and dark) respectively.60 healthy female mice were randomly divided into 10 groups with 6 mice per group. GroupⅠwas given distilled water intragastrically (i.g.) once daily for five days, served as control group. GroupⅡwas given gingerol i.g., served as gingerol group. GroupⅢ～Ⅰwere irradiated with 1,3,5,7 Gy of 60Co-γ-ray at the rate of 1.2 Gy/min respectively and given distilled water i.g. within 30 min after irradiation, served as radiation groups. GroupⅦ～Ⅹwere irradiated with 1,3,5,7 Gy of 60Co-y-ray respectively and given gingerol i.g. within 30 min after irradiation, served as radiation+gingerol groups. Gingerol was given at the dose of 800mg/kg B.W. once daily for 5 consecutive days. The animals were sacrificed for blood, liver, spleen and thighbone at 6th day post-irradiation.
Radiation could significantly reduce the relative spleen weight. Post-treatment of mice exposure to 3,5 Gy of radiation with gingerol significantly increased the spleen index compared to the 3,5 Gy radiation group, respectively. WBC in mice irradiated by 1 Gy ofγ-ray was lower than those with gingerol. Mice irradiated by 7 Gy ofγ-ray with gingerol showed higher RBC, HGB and HCT. Mice in radiation groups showed a dose-dependent depletion in the SOD activities and T-AOC, while elevation in the MDA contents. Treatment of mice with gingerol after 3 Gy of irradiation caused a significant elevation in the activities of SOD and total antioxidative capacity and depletion in the MDA levels in liver. The gingerol also showed a good therapeutic effect for 5 Gy irradiated mice. The numbers of micronuclei (MN) in the bone marrow polychromatic erythrocytes (PCEs) were significantly higher than control group and the gingerol can reduce the MN numbers in mice irradiated by 1,3,5 Gy ofγ-ray. These findings indicated that gingerol has the therapeutic effects against hematopoietic suppression and antioxidative function damage suffered from different doses of irradiation.
现阶段临床应用的抗辐射药物虽然疗效明显,但存在用药量大、毒副作用强等缺点。近年来辐射防治剂的研究热点逐渐转向抗辐射天然药物及功能食品的研究。生姜作为一种重要的中草药和日常饮食调味剂,具有镇静止吐,抑菌抗炎,降血糖、血脂和抗动脉硬化,抗氧化和清除自由基,抗肿瘤和增强免疫等功效。本研究将在已有的生姜辐射防护研究的基础上,进一步研究生姜提取物——姜辣素对不同剂量电离辐射(60~Co-γ射线)引起的造血系统和抗氧化系统损伤的治疗作用。
本研究选用60只健康雌性昆明小白鼠(6～8周龄,体重25～30 g),随机分为10组,每组6只,1组为对照组、2组为给药组,3-6组为照射组、7-10组为照射给药组。小鼠适应饲养一周后,3-10组小鼠进行照射,照射当天记为0天。3-6组分别接受1、3、5、7 Gy 60Co-γ射线照射,剂量率0.8 Gy/min,单次全身均匀照射。相同方法照射7-10组小鼠,并于照后30-60 min内灌胃姜辣素(800 mg/kg B.W.),总体积0.5 mL,连续5天(1次/天),3-6组小鼠灌胃同体积的蒸馏水。实验第6天颈椎脱臼处死小鼠,取血液、肝脏、脾脏、两侧股骨,以测定血常规、脏器指数、骨髓中DNA含量、骨髓嗜多染红细胞微核数目以及肝脏中SOD活性、T-AOC和MDA含量。本研究所得结果如下：
1.与对照组相比,给药组小鼠的脏器指数、DNA系数、肝脏中SOD活性和T-AOC能力均有不同程度的升高,外周血中红细胞、白细胞、淋巴细胞等血细胞含量有所升高,骨髓嗜多染红细胞中微核数目、肝脏MDA水平显著降低(p<0.05)。
2.60Co-γ射线照射后,小鼠肝脏指数的变化不大；与肝脏相比,脾脏对射线比较敏感,1 Gyγ射线即可引起脾脏指数显著低于对照组(p<0.01)。姜辣素可以提高小鼠脏器指数,尤其对3和5 Gy照射后脾脏指数降低能起到治疗效果(p<0.01)。
3.随着照射剂量的增大,照射组小鼠外周血中红细胞总数、血红蛋白含量、红细胞比积、白细胞总数、淋巴细胞比例逐渐降低。各剂量照射给药组小鼠血液中RBC、HGB、HCT、WBC、LYM含量均高于同剂量照射组,其中7 Gy照射给药组红细胞总数、血红蛋白含量、红细胞比积显著高于7 Gy照射组(p<0.05)；1 Gy照射给药组小鼠白细胞总数显著高于1 Gy照射组(p<0.05)。
4.不同剂量射线可不同程度地降低小鼠肝脏SOD酶活性和T-AOC能力,提高MDA含量。与对照组相比,5、7 Gy剂量照射组肝脏SOD酶活性显著降低(p<0.01),T-AOC能力也有所降低。各照射给药组小鼠肝脏SOD酶活性相比同剂量照射组SOD酶活性均有所升高,其中3 Gy照射给药组肝脏SOD酶活性显著高于3Gy照射组(p<0.05)；并且,3 Gy照射给药组T-AOC能力极显著高于3 Gy照射组(p<0.01),5 Gy照射给药组小鼠肝脏T-AOC能力显著高于5 Gy照射组(p<0.05)；1、3、5 Gy照射组小鼠肝脏MDA含量显著高于对照组(p
综上所述,姜辣素对不同剂量Y射线引起的造血系统和抗氧化系统辐射损伤有一定的治疗作用,尤其对3和5 Gy射线损伤小鼠的治疗效果较好。一方面,姜辣素增强了机体抗氧化能力,减少了射线对机体的损伤；另一方面,姜辣素提高了外周血中各种血细胞的数量,可维持机体正常功能代谢,减少各种放射病的发生；再者,姜辣素能提高骨髓DNA系数,减少微核数目,说明姜辣素可以阻止射线对遗传物质的损伤,促进DNA合成和修复,为机体其他器官系统的辐射后修复打下基础。
Radiation has been one heavy contamination around our everyday life. It can hurt cells, tissues and organs, even the whole body's function and metabolism through physical, chemical and biological mechanisms, which can bring acute and chronic radiation sickness. The hematopoietic system is the most sensitive to radiation. As one important Chinese medicine and flavoring, Ginger rhizome (ZOE) has been reported for its diminishing inflammation, treating vomit, antioxidation, antitumor, improving immunity and radical scavenging abilities. The therapetic effect of gingerol on radiated mice is further studied in this research.
6 to 8 weeks old Kunming mice weighing 25～30 g were selected from an inbred colony maintained under controlled conditions of temperature (23±2℃), humidity (50±5%) and light (14 and 10 hours of light and dark) respectively.60 healthy female mice were randomly divided into 10 groups with 6 mice per group. GroupⅠwas given distilled water intragastrically (i.g.) once daily for five days, served as control group. GroupⅡwas given gingerol i.g., served as gingerol group. GroupⅢ～Ⅰwere irradiated with 1,3,5,7 Gy of 60Co-γ-ray at the rate of 1.2 Gy/min respectively and given distilled water i.g. within 30 min after irradiation, served as radiation groups. GroupⅦ～Ⅹwere irradiated with 1,3,5,7 Gy of 60Co-y-ray respectively and given gingerol i.g. within 30 min after irradiation, served as radiation+gingerol groups. Gingerol was given at the dose of 800mg/kg B.W. once daily for 5 consecutive days. The animals were sacrificed for blood, liver, spleen and thighbone at 6th day post-irradiation.
Radiation could significantly reduce the relative spleen weight. Post-treatment of mice exposure to 3,5 Gy of radiation with gingerol significantly increased the spleen index compared to the 3,5 Gy radiation group, respectively. WBC in mice irradiated by 1 Gy ofγ-ray was lower than those with gingerol. Mice irradiated by 7 Gy ofγ-ray with gingerol showed higher RBC, HGB and HCT. Mice in radiation groups showed a dose-dependent depletion in the SOD activities and T-AOC, while elevation in the MDA contents. Treatment of mice with gingerol after 3 Gy of irradiation caused a significant elevation in the activities of SOD and total antioxidative capacity and depletion in the MDA levels in liver. The gingerol also showed a good therapeutic effect for 5 Gy irradiated mice. The numbers of micronuclei (MN) in the bone marrow polychromatic erythrocytes (PCEs) were significantly higher than control group and the gingerol can reduce the MN numbers in mice irradiated by 1,3,5 Gy ofγ-ray. These findings indicated that gingerol has the therapeutic effects against hematopoietic suppression and antioxidative function damage suffered from different doses of irradiation.
引文
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