摘要
目的:观察有氧运动联合雷氏大疣蛛毒素对小鼠皮下移植H22肝肿瘤中PI3K/Akt/mTOR信号通路及相关细胞因子差异表达的影响及其分子机制。方法:40只雄性KM小鼠随机均分为模型组(M组)、有氧运动组(E组)、负重有氧运动组(OE组)和有氧运动联合雷氏大疣蛛毒素组(E+MR组)。采用小鼠颈部皮下移植成瘤模型,各干预组于建模成功后第3天进行雷氏大疣蛛毒素和运动干预。尾静脉注射0.3 ml雷氏大疣蛛毒素(药剂浓度为2μg/g体重)连续20天;运动干预采用有氧游泳训练,每周6次,共5周。4组动物每4天测量1次肿瘤体积,并绘制肿瘤生长曲线。实验结束后小鼠禁食过夜,随后分离出肿瘤组织。采用HE染色对其进行显微结构形态学观察;免疫组化法检测肿瘤组织PI3K、Akt、mTOR、PTEN、IGF-1因子蛋白表达;实时荧光定量(Realtime-PCR)技术检测肿瘤组织PI3K、Akt、mTOR、PTEN、IGF-1mRNA表达。结果:①肿瘤体积测量结果显示:模型组肿瘤体积生长速度最快,有氧运动组肿瘤体积生长速度次之,负重有氧运动组肿瘤生长速度较有氧运动组生长速度慢,有氧运动联合雷氏大疣蛛毒素组生长速度最慢;②HE染色结果显示:模型对照组肿瘤细胞排列紧密、规整,有氧运动组细胞排列疏松欠规则,负重有氧运动组细胞出现坏死区,有氧运动联合雷氏大疣蛛毒素干预组细胞可见较大坏死区域。③免疫组织化学染色结果显示:三个干预组小鼠肿瘤组织PTEN阳性表达均高于模型非干预组,而PI3K、Akt、mTOR、IGF-1阳性表达较模型组低(P<0.01)。④Real-time PCR检测结果显示:三个干预组小鼠肿瘤中PTEN mRNA表达明显高于模型非干预组(P<0.01),其中有氧运动联合雷氏大疣蛛毒素组PTEN mRNA表达水平最高。结论:有氧运动联合雷氏大疣蛛毒素与有氧运动、负重有氧运动,能提高PTEN的含量,降低促肝癌细胞增殖的有关因子以及上调肿瘤细胞凋亡和诱
Objective To observe the effects of aerobic exercise and exercise combined with spider Macrothele raveni on the tumor suppressor factor of mice with Hz liver cancer. Methods Forty male KM mice, were randomly divided into cancer model group （ M, n = 10 ）, aerobic exercise group （E, n= 10）, heavy load aerobic exercise group （OE,n=10）,and aerobic exercise combined with Macrothele raveni toxin group（E＋MR,n=10）. Mice in group M were constructed through subcutaneous transplantation. Based on the group M,mice in group E,OE and E＋MR underwent swimming 6 days per week for 5 weeks,while in group OE were additionally carried 2% body weight object during swimming, and in group E＋MR, 20- day injection of 0.3ml Macrothele raveni venom was additionally administered. Gross tumor volume in all mice was measured every four day. Tumor samples of all mice were collected after dispose ,and their pathological changes were observed by microscope. Expressions of PI3K,Akt,mTOR,PTEN and IGF-1 proteins were determined by SABC; and expressions of PI3K,Akt,mTOR,PTEN and IGF-1 mRNA by Real-time PCR. Results The growth velocity of gross tumor volume from high to low appeared in turn in group M,group E, group OE,and group E＋MR. Tumor cells in group E arranged loosely and irregular, and tumor necrotic area appeared in groups OE and E＋MR, especially in group E＋MR. The expression of PTEN was significantly higher and expressions of PI3K,Akt,mTOR,PTEN and IGF-1 mRNA were significantly lower in groups E,OE and E＋MR than in group M （P〈 0.01）. Conclusion The results indicated that aerobic exercise, especially combination of exercise and venom of spider Macrothele raveni reveals better effect on adjusting the expression of PTEN,reduces the relevant factors of the hepatocellular carcinoma proliferation, and thus resists the growth of liver tumor in mice.
出处
《中国运动医学杂志》
CAS
CSCD
北大核心
2013年第12期1074-1081,共8页
Chinese Journal of Sports Medicine
基金
湖南省卫生厅科研计划课题(B2010-153)
运动科学湖南省研究生培养创新基地开放基金课题项目(CXJD20130010)
体适能与运动康复湖南省重点实验室研究课题(12pfer002)
