人重组胰岛素样生长因子1对慢性阻塞性肺疾病大鼠膈肌细胞凋亡的保护作用及机制探讨

Preventive effect of rhIGF-1 on diaphgramatic muscle cell apoptosis in rats with chronic obstructive pulmonary disease and mechanism

目的探讨人重组胰岛素样生长因子1（rhIGF-1）对慢性阻塞性肺疾病（chronic obstructive pulmonary disease，COPD）大鼠膈肌细胞凋亡的保护作用及其可能机制。方法雄性Wistar大鼠45只，随机分为对照组（A组），COPD模型组（B组），COPD模型＋rhIGF-1干预组（C组），每组15只。第1天、第14天和第28天各组处死5只，取完整膈肌称重后用原位末端标记法测定各组膈肌细胞凋亡率，免疫组织化学法测定膈肌细胞Fas蛋白表达情况，RT-PCR检测各组膈肌细胞Fas基因表达水平。结果第28天后B、C组膈肌质量均小于A组，C组大于B组（P〈0．05）。同一时间点B、C组膈肌细胞凋亡率，Fas蛋白阳性细胞率及Fas基因表达水平均大于A组，C组小于B组（P〈0．05）。结论Fas／FasL介导的凋亡途径参与了膈肌凋亡的发生，rhIGF-1可能通过干预Fas／FasL途径减少了膈肌凋亡，对COPD大鼠的膈肌凋亡产生保护作用。

Objective To investigate the prevetive effect and mechanism of rhIGF-1 on apoptosis of diaphgramatic muscle cell in rats with chronic obstructive pulmonary disease（COPD）. Methods Forty-five male Wistar rats were randomly divided into control group（group A） ,COPD model group（group B） ,COPD model＋ rhIGF-1 intervention group （group C）, 15 in each group. Five rats in each group were killed respectively at a time on the first day, 14th,28th day. Take complete diaphragms to detect rate of apoptosis with TUNEL method, detect Fas protein expression with immunohistochemistry and detect Fas gene expression with RT-PCR after weighing. Results Twenty-eight days later,the mass of diaphragms of group B and C was lighter than that of group A（ P 〈0.05） ,group C heavier than group B（ P 〈0.05）. At the same time point,rate of apoptosis,Fas protein expression and Fas gene expression of group B and C were higher than those of group A, group C was lower than group B （ P 〈 0.05）. Conclusions Fas/FasL mediated apoptosis way involves in the diaphragm apoptosis,rhIGF-1 may interfere With Fas/FasL way to reduce the apoptosis of the diaphragm and may have a protective effect of diaphragm apoptosis.