钙蛋白酶抑制剂Calpeptin对慢性阻塞性肺疾病大鼠骨骼肌萎缩的抑制作用  

Inhibitory effects of Calpeptin on skeletal muscle atrophy in COPD rats

作　　者：刘待见[1] 刘剑波[1] LIU Daijian;LIU Jianbo(Department of Respiratory Diseases,the Second Affiliated Hospital,Zhengzhou University,Zhengzhou 450014)

机构地区：[1]郑州大学第二附属医院呼吸科,郑州450014

出　　处：《郑州大学学报（医学版）》2022年第1期125-130,共6页Journal of Zhengzhou University(Medical Sciences)

摘　　要：目的:探讨钙蛋白酶抑制剂Calpeptin对慢性阻塞性肺疾病(COPD)大鼠骨骼肌萎缩的抑制作用及机制。方法:大鼠随机分为模型组30只和健康对照组18只,模型组大鼠建立COPD模型。随机抽取6只COPD模型大鼠和6只健康对照组大鼠,行肺功能测定及肺组织病理检测,证实造模成功。剩余24只COPD模型大鼠随机分为Calpeptin干预组和阴性对照组各12只。Calpeptin干预组大鼠肌内注射Calpeptin,剂量2 mg/(kg·d),连续4周;同时,健康对照组和阴性对照组给予溶剂DMSO 0.2 mL。干预后1周和4周每组分别处死6只大鼠,完整分离大鼠趾长伸肌(EDL)并称重,HE染色法观察EDL及肺组织病理学改变;RT-PCR法测定各组大鼠EDL组织中Calpains、Atrogin-1、MuRF-1 mRNA的表达;测定EDL组织中钙蛋白酶活性及26S蛋白酶体活性。结果:与健康对照组比较,Calpeptin干预组和阴性对照组大鼠出现EDL质量下降(P<0.05)和肌肉萎缩,EDL组织中Calpains、Atrogin-1、MuRF-1 mRNA的表达、钙蛋白酶活性及26S蛋白酶体活性均增强(P<0.05);和阴性对照组比较,Calpeptin干预组大鼠EDL组织中Calpains、Atrogin-1、MuRF-1 mRNA的表达均降低(P<0.05),钙蛋白酶活性及26S蛋白酶体活性均减弱(P<0.05)。结论:钙蛋白酶抑制剂Calpeptin可以通过抑制蛋白降解途径,减轻COPD大鼠EDL萎缩。Aim:To investigate the inhibitory effect and mechanism of Calpeptin on skeletal muscle atrophy in rats with chronic obstructive pulmonary disease(COPD).Methods:Experimental rats were randomly allocated into model group(n=30)and healthy control group(n=18).COPD rats was established in the model group.Six COPD rats and 6 healthy control rats were randomly selected to take pulmonary function test(PFT)and pathological examination of lung tissue,which confirmed the successful modeling.The remaining 24 COPD rats were randomly allocated into Calpeptin intervention group(n=12)and negative control group(n=12).In Calpeptin intervention group,2 mg/(kg·d)Calpeptin was injected intramuscularly for 4 weeks.Meanwhile,in healthy control group and negative control group,0.2 mL solvent DMSO was injected intramuscularly.After 1 week and 4 weeks of intervention,6 rats in each group were respectively sacrificed and their extensor digitorum longus muscle(EDL)was completely isolated and weighed.The pathological changes of EDL and lung tissue were observed by HE staining.The expression amount of Calpains,Atrogin-1 and MuRF-1 mRNA in EDL was determined by RT-PCR.The activities of Calpain and 26S proteasome in EDL were determined.Results:Compared with healthy control group,the weight of EDL in Calpeptin intervention group and negative control group decreased(P<0.05),and skeletal muscle atrophy was observed,the expression of Calpains,Atrogin-1 and MuRF-1 mRNA in EDL was increased(P<0.05),so as the activities of Calpains and 26S proteasome(P<0.05).Compared with negative control group,the expression amount of Calpains,Atrogin-1 and MuRF-1 mRNA decreased in Calpeptin intervention group(P<0.05),so as the activities of Calpain and 26S proteasome(P<0.05).Conclusion:Calpeptin can reduce muscular dystrophy in EDL of COPD rats by inhibiting protein degradation pathway.

关 键 词：钙蛋白酶抑制剂 Calpeptin 慢性阻塞性肺疾病 骨骼肌萎缩 大鼠 

分 类 号：R536[医药卫生—内科学] R365[医药卫生—临床医学]