摘要
目的 观察大鼠烟雾暴露慢性阻塞性肺疾病(COPD)模型白细胞介素(IL)-4、干扰素γ(IFNγ)和基质金属蛋白酶9(MMP-9)、MMP-12、基质金属蛋白酶组织抑制剂1(TIMP-1)的表达及N-乙酰半胱氨酸(NAC)对其的影响。方法 Wistar大鼠30只,分为3组,每组10只;(1)A组(烟雾暴露COPD模型组):建立大鼠烟雾暴露COPD模型;(2)B组(NAC干预组):从烟雾暴露2个半月开始用NAC灌胃,800 mg/kg,1次/d;(3)C组:健康对照组。小动物肺功能仪测3组大鼠的肺功能。ELISA测支气管肺泡灌洗液(BALF)及肺组织中IL-4、IFNγ的含量,逆转录(RT)-PCR测肺组织中MMP-9、MMP-12、TIMP-1的表达。结果 (1)与C组比较,A组大鼠第0.3秒钟用力呼气容积(FEV0.3)/用力肺活量(FVC)、动态顺应性(Cdyn)降低,呼气阻力(Re)升高,肺平均内衬间隔(Lm)增加,平均肺泡数(MAN)减少(P<0.05);NAC干预后,FEV0.3/FVC、Cdyn、Re明显改善(P<0.05),Lm、MAN无变化。(2)与C组比较,A组大鼠肺组织中IL-4、IL-4/IFNγ比值升高,IFNγ降低(P<0.05),NAC干预后,IL-4/IFNγ比值降低,IFNγ升高(P<0.05),IL-4无明显变化;BALF中IL-4、IFNγ、IL-4/IFNγ比值无明显变化,NAC干预后,IL-4、IL-M/IFNγ比值无变化,IFNγ升高(P<0.05)。(3)与C组比较,A组大鼠肺组织中MMP-12mRNA表达增强,MMP-12/TIMP-1比值?
Objective To investigate the changes of interferon-γ(IFNγ) , interleukin (IL)-4, matrix metalloproteinase (MMP)-9, MMP-12 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 in smoke-induced chronic obstructive pulmonary disease ( COPD) rat models and the therapeutic effect of N-acetylcysteine (NAC). Methods Male Wistar rats were exposed to cigarette smoke for 3.5 months. NAC was given in the last month. Lung function was measured at the end of the study. The levels of IL-4 and IFNγin broncho-alveolar lavage fluid ( BALF) and lung tissues were determined by ELISA. The expression of MMP-9, MMP-12 and TIMP-1 mRNA in lung tissues were determined by RT-PCR. Results (1) In comparison with the control group, smoke exposed group presented a significant decrease in forced expiratory volume in 0. 3 second ( FEV0.3) / forced vital capacity ( FVC ) , dynamic lung compliance ( Cdyn) , mean alveolar numbers (MAN) and a significant increase in expiratory resistance (Re) , pulmonary mean linear intercept (Lm) (P<0. 05). After treatment with NAC, FEV0.3/FVC, Re and Cdyn were improved significantly (P < 0. 05 ). No significant changes were found in Lm and MAN (P >. 05). (2) In the lung tissues of smoke exposed group, IL-4 level was 10. 00 pg/ml, IFNγlevel was 19. 37 pg/ml, and the IL-4/IFNγ ratio was 0. 49. In the lung tissues of the control group, they were 4. 38 pg/ml, 54. 94 pg/ml and 0. 10,respectively. There were significant differences in these indexes between the smoke exposed group and the control group (P <0. 05). IL-4 level in the NAC group was 7. 99 pg/ml which was similar to that in the smoke exposed group ( P > 0. 05 ). IFNγ and IL-4/ IFNγ ratio were 43. 40 pg/ml and 0. 15, the former being significantly higher and the latter being significantly lower than those in the smoke exposed group (P <0. 05). (3) The expression of MMP-12 mRNA and MMP-12/TIMP-1 ratio in the smoke exposed group (0. 36,1. 21) were significantly higher than those in the control group (0. 24,0. 88) (P < 0.05). There was no difference in TIMP-1 (P > 05). The expression of MMP-12, TIMP-1 mRNA and the MMP-12/TIMP-1 ratio in NAC group were similar to those in the smoke exposed group (P > 0. 05). Conclusions (1) Cigarette smoke exposure increased IL-4 and decreased IFNγ. This may contribute to smoke-induced changes in lung function. NAC had no effect on IL-4, but increased IFNγ, and the IL-4/ IFNγ ratio returned to normal. This might be one of the mechanisms of NAC in improving lung function. (2) Cigarette smoke promoted MMP-12 gene expression and increased the MMP-12/TIMP-1 ratio. This may play a role in smoke-induced emphysema. NAC did not alter MMP-12/TIMP-1 ratio when given in the late phase of smoke exposure. This result could explain the emphysematous changes in the NAC group.
出处
《中华内科杂志》
CAS
CSCD
北大核心
2004年第8期595-599,共5页
Chinese Journal of Internal Medicine
