航天医学与医学工程

目的建立低氧暴露力竭运动小鼠模型,探究低氧预处理(HPC)减轻低氧暴露力竭运动小鼠心肌损伤的分子学机制。方法40只小鼠随机分为对照组(Con组)、模型组(MG组)、低氧预适应1组(HP1组)及低氧预适应2组(HP2组),采用低氧干预+力竭游泳实验建立低氧暴露运动模型。MG组小鼠进行低氧条件下力竭游泳实验建模,HP1组低氧力竭游泳造模前给予低氧预适应刺激,HP2组造模同时给予重复低氧预适应刺激,连续8周。末次实验后小鼠取血及心肌组织,ELISA法检测血清谷丙转氨酶(AST)、乳酸脱氢酶(LDH)、肌酸激酶(CK)、丙二醛(MDA)、超氧化物歧化酶(SOD)含量,实时定量PCR和Western Blot技术检测心肌组织HIF-1αmRNA表达及PRKACA/B、CREB1、JAK1、STATA3蛋白表达。结果与Con组比较,MG组小鼠生长速率及力竭游泳时间显著降低(P<0.05),血清AST、LDH、CK水平显著上升(P<0.05),MDA含量下降(P<0.05),SOD含量上升(P<0.05),心肌HIF-1αmRNA表达升高(P<0.05),JAK1、STAT3、PRKACA/B及CREB1蛋白表达均显著下降(P<0.05)。与MG组比较,HP1组及HP2组小鼠生长速率及力竭游泳时间显著升高(P<0.05),血清AST、LDH、CK水平下降(P<0.05)。HP1、HP2组心肌组织PRKACA/B、CREB1、JAK1、STATA3蛋白表达水平显著高于MG组(P<0.05),HIF-1αmRNA表达显著低于MG组(P<0.05)。结论低氧预处理可能通过上调PKA/CREB及JAK1/STATA3信号通路相关组分蛋白,并下调心肌组织HIF-1αmRNA表达水平,以促进低氧暴露力竭运动小鼠心肌损伤的恢复进程。

Objective By establishing a hypoxia-exhaustive exercise mouse model,the molecular mechanism of hypoxia preconditioning(HPC)to alleviate myocardial injury in hypoxic-exhaustive exercise mice was explored.Methods Forty mice were randomly divided into the control group(Con group),the model group(MG group),the hypoxia pretreatment group 1(HP1 group)and the hypoxia pretreatment group 2(HP2 group).Hypoxia intervention+exhaustive swimming experiment were used to establish the hypoxic exposure exercise model.Mice in the MG group underwent exhaustive swimming experiment intervention under hypoxic conditions,the HP1 group underwent exhaustive swimming experiment under hypoxic conditions while giving hypoxic preconditioning stimulation,the HP2 group underwent an exhaustive swimming experiment under hypoxic conditions and repeated hypoxic preconditioning stimulation for 8 consecutive weeks.After the last experiment,the serum and myocardial tissues of the mice were taken.ELISA method was used to test the alanine aminotransferase(AST),lactate dehydrogenase(LDH),creatine kinase(CK),malondialdehyde(MDA),superoxide dismutase(SOD),while real-time PCR and western blot technology were used to detect HIF-1αmRNA expression and PRKACA/B,CREB1,JAK1,STATA3 protein expression.Results Compared with the Con group,the growth rate and exhausted swimming time of the MG group significantly decreased(P<0.05),serum myocardial enzymes(AST,LDH,CK)levels increased significantly(P<0.05),MDA levels significantly decreased(P<0.05),SOD level increased significantly(P<0.05),myocardial tissue HIF-1αmRNA expression level increased significantly(P<0.05),myocardial tissue JAK1,STAT3,PRKACA/B and CREB1 protein expression significantly decreased(P<0.05).Compared with MG group,the growth rate and exhaustive swimming time of mice in HP1 and HP2 group increased significantly(P<0.05),serum AST,LDH,CK levels decreased significantly(P<0.05),Myocardial tissue PRKACA/B,CREB1,JAK1,STATA3 protein expression levels were significantly higher(P<0.05),and myocardial tissue HIF-1αmRNA expression levels were significantly lower(P<0.05).Conclusion Hypoxic preconditioning may increase the PKA/CREB and JAK1/STATA3 signaling pathway related component proteins and down-regulate the expression level of HIF-1αmRNA in myocardial tissue,thus promote the recovery process of myocardial injury in mice exposed to hypoxic exhaustion.