VitC、NAC对C_2C_（12）细胞增殖和凋亡的影响
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摘要
目的:制备慢性阻塞性肺疾病(COPD)大鼠模型,观察膈肌、趾长伸肌的凋亡率以及各试验组血清中丙二醛的含量;以抗氧化剂VitC、N-乙酰半胱氨酸(NAC)对体外培养的骨骼肌成肌细胞(C_2C_(12))进行干预,探讨抗氧化剂对C_2C_(12)细胞增殖、凋亡的影响。
方法:经检疫合格的Wistar单纯雄性大鼠100只随机分为模型组80只,对照组20只。模型组采用熏香烟加气管内滴入猪胰弹性蛋白酶(PPE)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PPE的同时采用同一术式在气管内注入等量的无菌生理盐水,其它饲养条件等同。模型制作成功后,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,将大鼠重新分为健康对照组、COPD模型营养正常组、COPD模型营养不良组共三组,行肺功能测定处死大鼠后,每组随机选取18只大鼠取血清、膈肌以及趾长伸肌标本,进行以下测定:
1.采用硫代巴比妥酸(TBA)比色法测定血清中丙二醛(MDA)的含量;
2.脱氧核糖核苷酸末端转移酶介导的缺口末端标记法(TUNEL)测定大鼠膈肌、趾长伸肌凋亡率;
3.体外培养C_2C_(12)细胞,观察抗氧化剂VitC、NAC对C_2C_(12)细胞的生长曲线以及以Annexin V-PI双染法测C_2C_(12)细胞凋亡率。
结果:(1)肺功能检测示COPD组大鼠FEV_(0.3)(ml)、FEV_(0.3)/FVC(%)以及PEF(ml/s)均低于对照组(P均＜0.01),说明存在明显气流受限;COPD组大鼠肺组织经HE染色符合COPD病理改变;(2)COPD营养不良组膈肌、趾长伸肌的凋亡率明显增加,有统计学意义(P＜0.01);(3)COPD营养不良组较COPD营养正常组、对照组大鼠血清中反映氧化物的丙二醛含量明显增高(P＜0.001);(4)抗氧化剂VitC和NAC都显示了对体外培养的处于氧化应激状态C_2C_(12)细胞具有抑制凋亡的作用(P＜0.001),干预36h时高浓度的VitC比单纯DMEM/F12培养基有促进C_2C_(12)细胞增殖的作用(1.292±0.026,1.208±0.085,P＜0.05);(5)细胞流式法表明,抗氧化剂能够抑制C_2C_(12)细胞的凋亡,高浓度的VitC凋亡率最低。
结论:(1)COPD模型鼠体内活性氧产生增多,膈肌和趾长伸肌凋亡率增加,提示氧化应激可能导致了呼吸肌等骨骼肌细胞凋亡;(2)体外细胞培养表明,VitC、NAC能够抑制处于氧化应激状态的C_2C_(12)细胞的凋亡,而且高浓度的VitC可能对C_2C_(12)细胞有增殖作用。
Objective:To investigate the apotosis of diaphragmatic muscle and extensor digitorum longus,and analysis the serum levels of malondialdehyde(MDA)in a rat model of chronic obstructive pulmonary disease(COPD).To explore the effect of antioxidative,VitC and N-acetylcysteine,on the proliferation and apotosis of myoblast(C_2C_(12)).
Methods:One hundred male Wistar rats were randomly divided into groups:normal control group(n=20)and a COPD model group.The methods,which were that exposing to cigarette smoke and intratracheal instillation of PPE(20u/100g),were used to produce the rat model of COPD.While the control group was not exposed to smoke but was intratracheal instilled of the same amount of saline when the model group was accepted to PPE.We presumed,when the weight of the COPD model group was lower than 90%of the mean levels of the control group's, malnutrition with COPD rat occurred.Then the model was succeded comepletly,and re-divided into 3 groups:the control group,the non-malnutrition group with COPD and the malnutrition group.At last, all of the 54 rats were euthanized.We measured:
1)the serum levels of MDA by TBA.
2)And the apotosis radio in disphragmatic muscle and extensor digitorum longus by terminal-deoxynucleotidyl transferase mediated nick end labeling(TUNEL).
3)the effect of antioxidant,VitC and N-acetylcysteine,on the proliferation and apotosis of myoblast(C_2C_(12)).
Results:(1)Lung function tests showed that FEV_(0.3),FEV_(0.3)/FVC and PEF values were significantly lower in the COPD group than that of the control(all P＜0.01),and pathological changes of the model group consistented with that of COPD in the mankind.(2)And the apotosis radio of disphragmatic muscle and extensor digitorum longus in the malnutrition of COPD model group increased.(3)The serum levels of MDA significantly increased as compared with the others.(4)VitC and N-acetylcysteine,as the effective antioxidant,displayed that the protection for inhibiting the myoblast's apotosis,especially the high concentration of VitC.And VitC could promote the proliferation of myoblast occupying oxdative stress.
Conclusion:(1)The production of reactive oxygen species was increased in the malnutrition group with COPD,which maybe induces the apotosis of muscle,such as d;isphragmatic muscle and extensor digitorum longus.(2)Inhibiting the myoblast's apotosis and promoting the proliferation,VitC may be more effective.
方法:经检疫合格的Wistar单纯雄性大鼠100只随机分为模型组80只,对照组20只。模型组采用熏香烟加气管内滴入猪胰弹性蛋白酶(PPE)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PPE的同时采用同一术式在气管内注入等量的无菌生理盐水,其它饲养条件等同。模型制作成功后,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,将大鼠重新分为健康对照组、COPD模型营养正常组、COPD模型营养不良组共三组,行肺功能测定处死大鼠后,每组随机选取18只大鼠取血清、膈肌以及趾长伸肌标本,进行以下测定:
1.采用硫代巴比妥酸(TBA)比色法测定血清中丙二醛(MDA)的含量;
2.脱氧核糖核苷酸末端转移酶介导的缺口末端标记法(TUNEL)测定大鼠膈肌、趾长伸肌凋亡率;
3.体外培养C_2C_(12)细胞,观察抗氧化剂VitC、NAC对C_2C_(12)细胞的生长曲线以及以Annexin V-PI双染法测C_2C_(12)细胞凋亡率。
结果:(1)肺功能检测示COPD组大鼠FEV_(0.3)(ml)、FEV_(0.3)/FVC(%)以及PEF(ml/s)均低于对照组(P均＜0.01),说明存在明显气流受限;COPD组大鼠肺组织经HE染色符合COPD病理改变;(2)COPD营养不良组膈肌、趾长伸肌的凋亡率明显增加,有统计学意义(P＜0.01);(3)COPD营养不良组较COPD营养正常组、对照组大鼠血清中反映氧化物的丙二醛含量明显增高(P＜0.001);(4)抗氧化剂VitC和NAC都显示了对体外培养的处于氧化应激状态C_2C_(12)细胞具有抑制凋亡的作用(P＜0.001),干预36h时高浓度的VitC比单纯DMEM/F12培养基有促进C_2C_(12)细胞增殖的作用(1.292±0.026,1.208±0.085,P＜0.05);(5)细胞流式法表明,抗氧化剂能够抑制C_2C_(12)细胞的凋亡,高浓度的VitC凋亡率最低。
结论:(1)COPD模型鼠体内活性氧产生增多,膈肌和趾长伸肌凋亡率增加,提示氧化应激可能导致了呼吸肌等骨骼肌细胞凋亡;(2)体外细胞培养表明,VitC、NAC能够抑制处于氧化应激状态的C_2C_(12)细胞的凋亡,而且高浓度的VitC可能对C_2C_(12)细胞有增殖作用。
Objective:To investigate the apotosis of diaphragmatic muscle and extensor digitorum longus,and analysis the serum levels of malondialdehyde(MDA)in a rat model of chronic obstructive pulmonary disease(COPD).To explore the effect of antioxidative,VitC and N-acetylcysteine,on the proliferation and apotosis of myoblast(C_2C_(12)).
Methods:One hundred male Wistar rats were randomly divided into groups:normal control group(n=20)and a COPD model group.The methods,which were that exposing to cigarette smoke and intratracheal instillation of PPE(20u/100g),were used to produce the rat model of COPD.While the control group was not exposed to smoke but was intratracheal instilled of the same amount of saline when the model group was accepted to PPE.We presumed,when the weight of the COPD model group was lower than 90%of the mean levels of the control group's, malnutrition with COPD rat occurred.Then the model was succeded comepletly,and re-divided into 3 groups:the control group,the non-malnutrition group with COPD and the malnutrition group.At last, all of the 54 rats were euthanized.We measured:
1)the serum levels of MDA by TBA.
2)And the apotosis radio in disphragmatic muscle and extensor digitorum longus by terminal-deoxynucleotidyl transferase mediated nick end labeling(TUNEL).
3)the effect of antioxidant,VitC and N-acetylcysteine,on the proliferation and apotosis of myoblast(C_2C_(12)).
Results:(1)Lung function tests showed that FEV_(0.3),FEV_(0.3)/FVC and PEF values were significantly lower in the COPD group than that of the control(all P＜0.01),and pathological changes of the model group consistented with that of COPD in the mankind.(2)And the apotosis radio of disphragmatic muscle and extensor digitorum longus in the malnutrition of COPD model group increased.(3)The serum levels of MDA significantly increased as compared with the others.(4)VitC and N-acetylcysteine,as the effective antioxidant,displayed that the protection for inhibiting the myoblast's apotosis,especially the high concentration of VitC.And VitC could promote the proliferation of myoblast occupying oxdative stress.
Conclusion:(1)The production of reactive oxygen species was increased in the malnutrition group with COPD,which maybe induces the apotosis of muscle,such as d;isphragmatic muscle and extensor digitorum longus.(2)Inhibiting the myoblast's apotosis and promoting the proliferation,VitC may be more effective.
引文
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