CAJ | 학술논문

目的观察慢性阻塞性肺疾病(COPD)大鼠支气管肺组织转化生长因子(TGF)-β1和胶原表达的变化特点以及两者相关的关系,探讨阿托伐他汀对支气管肺组织TGF-β1和胶原表达的干预作用.方法将雄性SD大鼠分成3组(健康对照组、COPD模型组和阿托伐他汀干预组),10周后用小动物肺功能仪测定气道阻力(RL)和动态顺应性(Cdyn);观察各组大鼠支气管肺组织的病理特征;测定支气管肺组织的胶原表达率和TGF-β1含量.比较各组支气管肺组织TGF-β1含量,支气管肺组织中胶原的表达率,以及两者相关性.结果(1)COPD模型组基本符合人类COPD病理生理变化.外周细支气管平滑肌层和细胞外基质胶原较健康对照组大鼠明显增多.阿托伐他汀干预组与COPD模型组比较,RL减少(P<0.01),Cdyn增加(P<0.01).(2)COPD模型组TGF-β1蛋白(5.66±0.35)μg·L-1,较阿托伐他汀干预组(3.25±0.69)μg·L-1升高明显(P<0.01),健康对照组(1.62±0.46)μg· L-1,与另两组相比降低明显(均P<0.01).(3)COPD模型组支气管肺组织胶原表达率为(17.18±5.34)%,较健康对照组[(7.42±2.97)%]增高(P<0.01),阿托伐他汀干预组为(11.94±4.03)%,较健康对照组升高(P<0.05),但较COPD模型组降低(P<0.01).(4)各组支气管肺组织TGF-β1含量与胶原表达率呈显著正相关(r=0.802,P<0.01).结论(1)慢性烟薰和气道内滴入LPS能构建含有气道重构特征的C0PD大鼠模型.(2)支气管肺组织胶原沉积增多是COPD气道重构的重要病理变化.胶原表达率与TGF-β1呈正相关,表明TGF-β1在COPD气道重构中起重要作用.(3)早期应用阿托伐他汀可明显抑制气道TGF-β1的表达,影响COPD大鼠气道重构的发生、发展.
목적관찰만성조새성폐질병(COPD)대서지기관폐조직전화생장인자(TGF)-β1화효원표체적변화특점이급량자상관적관계,탐토아탁벌타정대지기관폐조직TGF-β1화효원표체적간예작용.방법장웅성SD대서분성3조(건강대조조、COPD모형조화아탁벌타정간예조),10주후용소동물폐공능의측정기도조력(RL)화동태순응성(Cdyn);관찰각조대서지기관폐조직적병리특정;측정지기관폐조직적효원표체솔화TGF-β1함량.비교각조지기관폐조직TGF-β1함량,지기관폐조직중효원적표체솔,이급량자상관성.결과(1)COPD모형조기본부합인류COPD병리생리변화.외주세지기관평활기층화세포외기질효원교건강대조조대서명현증다.아탁벌타정간예조여COPD모형조비교,RL감소(P<0.01),Cdyn증가(P<0.01).(2)COPD모형조TGF-β1단백(5.66±0.35)μg·L-1,교아탁벌타정간예조(3.25±0.69)μg·L-1승고명현(P<0.01),건강대조조(1.62±0.46)μg· L-1,여령량조상비강저명현(균P<0.01).(3)COPD모형조지기관폐조직효원표체솔위(17.18±5.34)%,교건강대조조[(7.42±2.97)%]증고(P<0.01),아탁벌타정간예조위(11.94±4.03)%,교건강대조조승고(P<0.05),단교COPD모형조강저(P<0.01).(4)각조지기관폐조직TGF-β1함량여효원표체솔정현저정상관(r=0.802,P<0.01).결론(1)만성연훈화기도내적입LPS능구건함유기도중구특정적C0PD대서모형.(2)지기관폐조직효원침적증다시COPD기도중구적중요병리변화.효원표체솔여TGF-β1정정상관,표명TGF-β1재COPD기도중구중기중요작용.(3)조기응용아탁벌타정가명현억제기도TGF-β1적표체,영향COPD대서기도중구적발생、발전.
Objective To investigate the effect of atorvastatin on the expression of transforming growth factor-β1 (TGF-β1) and col agen in rat model of chronic obstructive pulmonary disease (COPD). Methods Male SD rats were divided in-to three groups; control group, COPD model group and atorvastatin intervention group. After 10 weeks,airway resistance (RL) and dynamic compliance (Cdyn) was measured;the pathological features of lung tissue of three groups were observed;the ex-pressions of TGF-β1 and col agen content in bronchial and lung tissue were measured. Results In COPD model the peripheral bronchiolar smooth muscle layer and collagen in extracel ular matrix increased significantly compared to the healthy control group. In intervention group RL reduced (P<0.01) and Cdyn increased (P<0.01) compared to model group. The expressions of TGF-β1 of COPD model group was 5.66±0.35/μg·L-1, which was significantly higher than that in intervention group (3.25± 0.69/μg·L-1, P<0.01) and healthy control group (1.62±0.46/μg·L-1, P<0.01). The expression of col agen of bronchial and pul-monary tissue in COPD group was (17.18 ± 5.34)%, which was higher than that in healthy group (7.42±2.97%, P<0.01), the expression of col agen of intervention group was (11.94 ± 4.03)%, which was higher than that in healthy group(P<0.05) and low-er than that in COPD group (P<0.01). The expression of TGF-β1 was positively correlated with collagen expression in bronchial and pulmonary tissue (r=0.802, P<0.01). Conclusion The increased col agen deposition in bronchial and pulmonary tissue is an important pathological changes of COPD airway remodeling, which is associated with up-regulation of TGF-β1 expression. Early administration of atorvastatin can significantly inhibit TGF-β1 expression and interfere in the development of COPD rat air-way remodeling.