低氧和运动干预对肥胖小鼠心肌组织Ghrelin-GHSR通路及相关蛋白的影响  

The Effect Hypoxic and Training Intervention on Ghrelin-GHSR Pathway and Related Proteins in Myocardial Tissues of Obese Mice

作　　者：王腾生 付鹏宇 朱镕鑫 于晶晶 郜瑞睿 龚丽景 Wang Tengsheng;Fu Pengyu;Zhu Rongxin;Yu Jingjing;Cao Ruirui;Cong Lijing(Key Laboratory of Sports and Physical Health of the Ministry of Education,Bejing Sport University,Beijing 100084,China;Department of Physical Education,Northwestern Polytechnical University,Xi'an 710072,China;Shanghai Research Institute of Sports Science,Shanghai 2000302,China;Sport Science School,Beijing Sport University,Beijing 100084,China;China Institute of Sport and Health Science,Beijing Sport University,Beijing 100084,China)

机构地区：[1]北京体育大学运动与体质健康教育部重点实验室,北京100084 [2]西北工业大学体育部,陕西西安710072 [3]上海体育科学研究所,上海2000302 [4]北京体育大学运动人体科学学院,北京100084 [5]北京体育大学中国运动与健康研究院,北京100084

出　　处：《中国运动医学杂志》2023年第6期460-469,共10页Chinese Journal of Sports Medicine

基　　金：北京体育大学本科教育教学研究与改革课题(BSUJG2022KCJSA10);北京市大学生创新创业训练计划项目(S202310043002)。

摘　　要：目的:探究低氧和运动干预改善肥胖小鼠心肌损伤程度和对胃饥饿素-生长激素促分泌激素受体(Ghrelin-GHSR)通路及相关蛋白的影响。方法:50只雄性C57BL/6J小鼠随机分为普通对照组(N组,n=8,饲喂普通饲料)和高脂膳食组(H组,n=42,饲喂高脂饲料8周以建立肥胖模型)。将建模成功后的肥胖小鼠随机分为肥胖对照组(HN组,n=7)、肥胖常氧运动组(HE组,n=7)、肥胖低氧暴露组(HHN组,n=8)和肥胖低氧运动组(HHE组,n=7)。HE和HHE组进行1 h/次/天、速度12 m/min的跑台训练;HHN和HHE组进行11.2%O_(2)暴露,8 h/次/天,6次/周。4周后,测试血糖血脂水平;HE染色观察心肌组织形态,免疫组化染色观察Ghrelin蛋白水平和分布;RT-PCR和Western blotting法分别检测心肌组织中Ghrelin、GHSR-1a、Ghrelin O-酰基转移酶(GOAT)、心肌肌钙蛋白I3基因(TNNI3)、神经肽Y1R(NPY1R)、血管内皮生长因子A(VEGFA)mRNA和蛋白的表达。结果:(1)HE和HHN组体重较HN组显著降低(P<0.05);HN组血糖(GLU)、甘油三酯(TG)、总胆固醇(TC)、游离脂肪酸(FFA)和低密度脂蛋白胆固醇(LDL-C)水平显著高于N组,高密度脂蛋白胆固醇(HDL-C)水平显著低于N组(P<0.05);HE和HHN组GLU水平显著低于HN组,HHN组TC水平显著低于HN组(P<0.05);HHE组GLU和TC水平显著低于HE组,LDL-C水平显著低于HN组(P<0.05);HE、HHN和HHE三组FFA水平显著低于HN组,HDL-C水平显著高于HN组(P<0.05)。(2)HN组较N组出现心肌细胞肥大和心肌纤维形态改变及强嗜酸性染色,损伤评分显著升高(P<0.05);HHE组心肌形态明显改善,且损伤评分显著低于HN组和HE组(P<0.05);HHN组损伤评分高于HE组(P<0.05);HHE组Ghrelin在心肌组织中表达量显著高于HN组(P<0.05)。(3)HN组心肌Ghrelin和GHSR-1a mRNA表达水平较N组显著降低(P<0.05);HE组Ghrelin、GHSR-1a、GOAT和VEGFA mRNA水平显著高于HN组(P<0.05);HE组TNNI3 mRNA表达水平显著低于HN组(P<0.05);HHE组Ghrelin、GHSR-1a和VEGFA mRNA表达水平分别显著高�Objective To explore the extent of hypoxic and training to ameliorate myocardial injury and their effects on the related genes and protein expressions of the Chrelin-Growth Hormone Secretagogue Receptor(Ghrelin-CHSR)pathway in obese mice.Methods Fifty male C57BL/6J mice were randomly divided into a normal control(N)group of 8 and a high-fat diet(H)group of 42.Group N were on normal diet,while group H were fed high-fat diet for 8 weeks to induce obesity.After successful modelling,group H was randomly divided into an obese control group(HN,n=7),an obese normoxia exercise group(HE,n=7),an obese hypoxia exposure group(HHN,n=8),and an obese hypoxia exercise group(HHE,n=7).Both the HE and HHE groups underwent daily 60-minute treadmill training at 12 m/min 6 times a week,while the HHN and HHE groups were exposed to a hypoxic chamber with 11.2%oxygen content 8 hours daily,6 times a week for 4 weeks.After the intervention,the levels of glucose(GLU),triglyceride(TG),total cholesterol(TC),free fat acid(FFA),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C)in the serum were tested.Moreover,the morphology of myocardial tissue was observed by using HE staining,while Ghrelin protein levels and distribution and were evaluated using immunohistochemical staining.Meanwhile,the mRNA and proteins expression of Ghrelin,growth hormone secretagogue receptor-1a(GHSR-1a),ghrelin O acyltransferase(COAT),troponin I type 3(TNNI3),neuropeptide Y1 receptor(NPYIR),vascular endothelial growth factor A(VEGFA)in the myocardial tissue were detected by usiing the reverse transcription-polymerase chain reaction and Western blotting,respectively.Results(1)After 4 weeks of intervention,the weight of mice in the HE,HHN,and HHE groups was significantly lower than the HN group(P<0.05),while the average GLU,TG,TC,FFA,and LDL-C levels of group HN were significantly higher than group N,but the average HDL-C level of the former was significantly lower than the later(P<0.05).Moreover,the average GLU and TC levels of the

关 键 词：低氧 运动 肥胖 心肌组织 GHRELIN 

分 类 号：R589.2[医药卫生—内分泌] G804.2[医药卫生—内科学]