COPD模型大鼠骨骼肌细胞凋亡及Bcl-2、Bax表达的实验研究
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摘要
目的:观察细胞凋亡对COPD模型大鼠骨骼肌萎缩影响及相关基因Bcl-2、Bax的表达。
方法:100只健康Wistar大鼠随机分为模型组80只,对照组20只。模型组采用1-29天,31-60天熏香烟,第30天气管内注入猪胰蛋白酶(PEE)的方法建立COPD大鼠模型。对照组不熏香烟,在模型组气管内注入PEE的同一天采用同一术式气管内注入等量生理盐水。继续饲养至第90天,以低于对照组大鼠平均体重的90%作为判断发生营养不良的标准,将实验大鼠分为:对照组、COPD营养正常组和COPD营养不良组。取大鼠膈肌、趾长伸肌制备石蜡切片,分别采用TUNEL法测定膈肌、趾长伸肌石蜡切片细胞凋亡率和免疫组织化学法测定Bcl-2、Bax表达,Image-Pro Plus version 6.0图像系统测定免疫组化表达强度,所得数据经SPSS 13.0软件进行单因素方差分析、t检验及相关性分析。
结果:1.COPD模型大鼠营养不良组膈肌、趾长伸肌的凋亡率均显著高于对照组(P＜0.01,P＜0.01)、COPD模型大鼠营养正常组(P＜0.01,P＜0.01)。三组大鼠膈肌凋亡率与趾长伸肌比较均无差异(P＞0.5)。2.对照组膈肌、趾长伸肌Bcl-2的表达均强于COPD模型大鼠营养正常组(P＜0.01,P＜0.01)、COPD模型大鼠营养不良组(P＜0.01,P＜0.01);COPD模型大鼠营养不良组膈肌、趾长伸肌的Bax表达均强于COPD模型大鼠营养正常组(P＜0.01,P＜0.01)、对照组(P＜0.01,P＜0.01)。三组大鼠膈肌Bcl-2、Bax与趾长伸肌比较均无差异(P＞0.5)。
结论:COPD模型大鼠存在明显骨骼肌凋率增加,细胞凋亡可能是COPD模型大鼠骨骼肌萎缩的重要机制。Bcl-2、Bax参与调节COPD模型大鼠骨骼肌凋亡。
Objective: To observe the impact of the apoptosis on the skeletal muscle atrophy and the expression of related genes Bcl-2 and Bax in rats with Chronic obstructive pulmonary disease(COPD).
Methods: 100 healthy male adult Wistar rats were randomly divided into two groups: normal control group (n=20) and model group (n=80). The COPD rat model was performed with intratracheal instillation of PEE (20u/100g.Bw) on the 30 day of the modeling and exposed to cigarette smoke for 60 days, 30 minutes per day. The control group was not exposed to smoke but was intratracheally instilled of the same amount of Physiologic Saline on the 30~(th) day. The model rats were continually raised for another 30 days. Malnutrition was defined when the weight of the rats in the model group was lower than 90% of the mean body weight of the control group. All model rats were re-divided into 3 groups: the control group, the non-malnutrition COPD group, the malnutrition COPD group. Diaphragmatic muscle and long extensor muscle digits from rats were taken to make paraffin section. The rates of muscle apoptosis were measured by TUNEL method, expression of related genes Bcl-2 and Bax by immunohistochemical method, and the intensity of the expression of Bcl-2 and Bax by Image-Pro Plus version 6.0 systerm to deal with the pictures. All the data was handled by SPSS 13.0 software through one-factor analysis of variance, t-test and related analysis.
Results: 1.The rates of muscle apoptosis in both diaphragmatic muscle and long extensor muscle digits of the malnutrition group were significantly higher than those of non-malnutrition group (P<0.01, P<0.01) and the control group (P<0.01, P<0.01). There were no significant differences between diaphragmatic muscle and long extensor muscle digits in the rates of muscle apoptosis of all three groups (P>0.05). 2. The expression of Bcl-2 in malnutrition group were significantly lower than those of non-malnutrition group (P<0.01, P<0.01) and the control group (P<0.01,P<0.01). The expression of Bax in malnutrition group were significantly higher than those of non-malnutrition group (P<0.01, P<0.01) and the control group (P<0.01, P<0.01). There were no significant differences between diaphragmatic muscle and long extensor muscle digits in the expression of Bcl-2 and Bax of all three groups (P>0.05).
Conclusion:
1. An significantly increase of rates of muscle apoptosis was found in COPD model rats. Apoptosis maybe the important mechanism in skeletal muscle atrophy of COPD model rats.
2. The genes Bcl-2 and Bax are the factors to adjust the muscle apoptosis of COPD model rats.
方法:100只健康Wistar大鼠随机分为模型组80只,对照组20只。模型组采用1-29天,31-60天熏香烟,第30天气管内注入猪胰蛋白酶(PEE)的方法建立COPD大鼠模型。对照组不熏香烟,在模型组气管内注入PEE的同一天采用同一术式气管内注入等量生理盐水。继续饲养至第90天,以低于对照组大鼠平均体重的90%作为判断发生营养不良的标准,将实验大鼠分为:对照组、COPD营养正常组和COPD营养不良组。取大鼠膈肌、趾长伸肌制备石蜡切片,分别采用TUNEL法测定膈肌、趾长伸肌石蜡切片细胞凋亡率和免疫组织化学法测定Bcl-2、Bax表达,Image-Pro Plus version 6.0图像系统测定免疫组化表达强度,所得数据经SPSS 13.0软件进行单因素方差分析、t检验及相关性分析。
结果:1.COPD模型大鼠营养不良组膈肌、趾长伸肌的凋亡率均显著高于对照组(P＜0.01,P＜0.01)、COPD模型大鼠营养正常组(P＜0.01,P＜0.01)。三组大鼠膈肌凋亡率与趾长伸肌比较均无差异(P＞0.5)。2.对照组膈肌、趾长伸肌Bcl-2的表达均强于COPD模型大鼠营养正常组(P＜0.01,P＜0.01)、COPD模型大鼠营养不良组(P＜0.01,P＜0.01);COPD模型大鼠营养不良组膈肌、趾长伸肌的Bax表达均强于COPD模型大鼠营养正常组(P＜0.01,P＜0.01)、对照组(P＜0.01,P＜0.01)。三组大鼠膈肌Bcl-2、Bax与趾长伸肌比较均无差异(P＞0.5)。
结论:COPD模型大鼠存在明显骨骼肌凋率增加,细胞凋亡可能是COPD模型大鼠骨骼肌萎缩的重要机制。Bcl-2、Bax参与调节COPD模型大鼠骨骼肌凋亡。
Objective: To observe the impact of the apoptosis on the skeletal muscle atrophy and the expression of related genes Bcl-2 and Bax in rats with Chronic obstructive pulmonary disease(COPD).
Methods: 100 healthy male adult Wistar rats were randomly divided into two groups: normal control group (n=20) and model group (n=80). The COPD rat model was performed with intratracheal instillation of PEE (20u/100g.Bw) on the 30 day of the modeling and exposed to cigarette smoke for 60 days, 30 minutes per day. The control group was not exposed to smoke but was intratracheally instilled of the same amount of Physiologic Saline on the 30~(th) day. The model rats were continually raised for another 30 days. Malnutrition was defined when the weight of the rats in the model group was lower than 90% of the mean body weight of the control group. All model rats were re-divided into 3 groups: the control group, the non-malnutrition COPD group, the malnutrition COPD group. Diaphragmatic muscle and long extensor muscle digits from rats were taken to make paraffin section. The rates of muscle apoptosis were measured by TUNEL method, expression of related genes Bcl-2 and Bax by immunohistochemical method, and the intensity of the expression of Bcl-2 and Bax by Image-Pro Plus version 6.0 systerm to deal with the pictures. All the data was handled by SPSS 13.0 software through one-factor analysis of variance, t-test and related analysis.
Results: 1.The rates of muscle apoptosis in both diaphragmatic muscle and long extensor muscle digits of the malnutrition group were significantly higher than those of non-malnutrition group (P<0.01, P<0.01) and the control group (P<0.01, P<0.01). There were no significant differences between diaphragmatic muscle and long extensor muscle digits in the rates of muscle apoptosis of all three groups (P>0.05). 2. The expression of Bcl-2 in malnutrition group were significantly lower than those of non-malnutrition group (P<0.01, P<0.01) and the control group (P<0.01,P<0.01). The expression of Bax in malnutrition group were significantly higher than those of non-malnutrition group (P<0.01, P<0.01) and the control group (P<0.01, P<0.01). There were no significant differences between diaphragmatic muscle and long extensor muscle digits in the expression of Bcl-2 and Bax of all three groups (P>0.05).
Conclusion:
1. An significantly increase of rates of muscle apoptosis was found in COPD model rats. Apoptosis maybe the important mechanism in skeletal muscle atrophy of COPD model rats.
2. The genes Bcl-2 and Bax are the factors to adjust the muscle apoptosis of COPD model rats.
引文
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[1]Brug J,Schols A,Mesters L.et al.Dietary change,nutrition education and chronic obstructive pulmonary disease.Patient Educ Couns,2004,52(3):249-257.
[2]Schols AM,Slangen J,Volovics L,et al.Weight loss is a reversible factor in the prognosis of chronic obstructive pulmonary disease.Am J Respir Crit Care med,1998,157(6pt1):1791-1797.
[3]Landbo C,Proscott E,Lange P,Vestbo J,et al.Prognosis valne of nutritional status in chronic obstructive pulmonary disease.Am J,Respir Crit Care Med.1999,166(6):809-813
[4]Schols AM,Socrets PB,Dingemans AMC,et al.Prevalcnce and characteristcs of mutritional depletion in patients with stable COPD eligible for pulmonary rehabilitation.Am Rev Respir Dis,1993,147:1151-1156.
[5]Zawallack RL,Shoup R,Warner S,et al.Alteration in total and regional body composition in patients with moderate to severe obstructive lung disease.Monsldi Arch Chesst Dis,1996,51:507-509.
[6]Shoup R,Dalsky G,Warner S.et al.Body composition and health related quality of life in patients with obstructive airway disease.Eur Respir.1997,10:1576-1580
[7]Marquis K,Debigare R,Lacesse Y,et al.Mid-thigh muscle cross-sectional area is a better predictor of mortality than body mass index in patients with chronic obstructive pulmonary disease.Am J respir Crit Care Med,2002,166:80-813
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