白介素15与慢性阻塞性肺疾病大鼠骨骼肌降解的相关性研究  

Skeletal muscle degradation of chronic obstructive pulmonary disease rats and relationship with interleukin-15

作　　者：关丽君[1] 刘朝晖[1] 梁志科[1] 马碧蔓[1] 曾祥富[1] 

机构地区：[1]广州医学院附属广州市第一人民医院呼吸内科,510180

出　　处：《国际呼吸杂志》2013年第13期979-985,共7页International Journal of Respiration

基　　金：广东省自然科学基金项目（10151006001000012）;广州市卫生局资助项目（30504382207）

摘　　要：目的 研究慢性阻塞性肺疾病（COPD）大鼠模型骨骼肌降解途径——泛素-蛋白酶体途径与白介素15（IL-15）的相关关系,为有效防治COPD患者骨骼肌蛋白高分解提供理论与依据.方法 成年雄性SD大鼠45只,分为模型组30只,健康组15只,采用反复熏香烟加气管内注入脂多糖法复制COPD大鼠动物模型.实时荧光定量PCR法和Western blot法分别检测大鼠膈肌、腓肠肌和肋间肌中E2-14K、MAFbx、Ub基因和蛋白表达.ELISA法检测大鼠血清、膈肌、腓肠和肋间肌中IL-15和肿瘤坏死因子α（TNF-α）的含量.结果 COPD模型大鼠膈肌、腓肠肌和肋间肌中E2 14K、MAFbx、Ub基因和蛋白表达分别较健康组升高.COPD模型组大鼠血清、膈肌、腓肠肌和肋间肌中IL-15、TNF-α的水平较健康组升高.大鼠血清、膈肌、腓肠肌和肋间肌中IL-15和TNF-α水平呈正相关（血清r=0.75;膈肌r =0.81;腓肠肌r=0.82;肋间肌r=0.78,P值均＜0.05）.膈肌、腓肠肌和肋间肌中IL-15均与E2-14K、MAFbx、Ub相对表达量呈正相关（膈肌r=0.88、r=0.86、r=0.87；腓肠肌r=0.85、r=0.87、r=0.76;肋间肌r=0.85、r =0.80、r=0.84,P值均＜0.05）.大鼠造模结束后体质量净增长与血清、膈肌、腓肠肌和肋间肌中IL-15呈负相关（血清r=-0.90,膈肌r=-0.85,腓肠肌r=-0.82,肋间肌r=-0.82,P＜0.05）.结论 在COPD模型大鼠中,IL-15可能通过TNF-α共同作用于泛素-蛋白酶体途径影响骨骼肌降解的作用.Objective To study the relationship of ubiquitin-proteasome pathway （UPP）and interleukin-15 （IL-15） in skeletal muscle degradation of COPD rats,in order to provide scientific theories for prevent increase protein degradation in skeletal muscle of COPD patients.Methods Forty-five healthy adult male SD rats were randomly divided into a COPD model group （n =30）and a normal control group （n =15）.The COPD rat model was established by exposure to cigarette smoke and instillation of lipopolysaccharide （LPS）.The mRNA and protein levels of E2-14K,MAFbx,Ub in diaphragm,gastrocnemius and intercostal muscle were measured by Real time fluorescence quantitative PCR and Western blot.The concentration of IL-15 and TNF-α in serum,diaphragm,gastrocnemius and intercostal muscle was measured by ELISA.Results The expression of mRNA and protein of E2-14K,MAFbx,Ub compared with the normal control group in diaphragm,gastrocnemius and intercostal muscle were all increased in the COPD model group.The IL-15 and TNF-α level in serum,diaphragm,gastrocnemius and intercostal muscle were higher in the COPD group than the control group.In serum,diaphragm,gastrocnemius and intercostal muscle,the level of IL-15 was positively correlated with TNF α（serum r =0.75,diaphragm r =0.81,gastrocnemius r =0.82,intercostal muscle r =0.78,P 〈0.05）.The level of IL-15 in diaphragm,gastrocnemius and intercostal muscle was positively correlated with the expression of E2-14K,MAFbx,Ub （diaphragm r =0.88,r =0.86,r =0.87;gastrocnemius r =0.85,r =0.87,r =0.76 ;intercostal muscle r =0.85,r =0.80,r =0.84,P 〈 0.05）.The level of IL-15 in diaphragm,gastrocnemius and intercostal muscle was negatively correlated with the body weight net growth of rats after COPD models were established （diaphragm r =-0.90,gastrocnemius r =-0.85,intercostal muscle r =-0.82,r =-0.82,P 〈0.05）.Conclusions In COPD rats,IL-15 may in company with TNF-αcontribute to impat skeletal muscle degradation through the ubiquitin proteasome pathway.

关 键 词：慢性阻塞性肺疾病 泛素-蛋白酶体途径 白介素15 肿瘤坏死因子Α 

分 类 号：R563[医药卫生—呼吸系统]