CAJ | 학술논문

目的研究白三烯受体拮抗剂(孟鲁司特)对支气管哮喘(简称哮喘)气道炎症和气道重塑的影响,揭示白三烯受体拮抗剂对血管内皮生长因子(VEGF)及其受体的调控作用.方法将24只清洁级雄性SD大鼠按随机数字表法分为对照组、哮喘组和干预组,每组8只.对照组采用生理盐水致敏和激发,哮喘组采用卵清白蛋白致敏和激发,干预组在采用卵清白蛋白致敏和激发前给予孟鲁司特灌胃.采用肺功能检测各组大鼠气道呼气阻力;采用酶联免疫吸附法(ELISA)对各组大鼠血清中VEGF和白三烯D<4>(LTD4)进行定量分析;用免疫组织化学方法检测VEGF、VEGF受体1(VEGFR1)及VEGFR:在大鼠肺组织内的表达水平.采用图像分析软件测定肺组织切片中的血管计数、血管平滑肌厚度.结果 (1)肺功能检测显示哮喘组平均呼气阻力显著升高;(2)对照组血清中VEGF和LTD4的水平分别为(17±5)ng/L和(6.1±0.7)ng/L,哮喘组分别为(31±6)ng/L和(10.7±3.5)ng/L,干预组分别为(15±4)ng/L和(9.8±1.6)ng/L,对照组和干预组分别与哮喘组比较差异有统计学意义(F值分别为63.78和39.56,均P<0.01);(3)免疫组织化学结果显示哮喘组VEGF及受体均大量表达,而对照组和干预组有较少表达.(4)图像分析显示,对照组、哮喘组和干预组的血管计数分别为14±2、22±2和16±4.(5)直线相关分析显示,血管计数与血清中VEGF的水平正相关(r=0.705,P<0.05).结论 VEGF及其受体在哮喘气道及肺内过度表达,参与了气道炎症和气道血管重塑的过程.孟鲁司特可能通过影响VEGF及其受体的表达影响气道炎症和气道血管重塑的病理生理过程.
목적 연구백삼희수체길항제(맹로사특)대지기관효천(간칭효천)기도염증화기도중소적영향,게시백삼희수체길항제대혈관내피생장인자(VEGF)급기수체적조공작용.방법 장24지청길급웅성SD대서안수궤수자표법분위대조조、효천조화간예조,매조8지.대조조채용생리염수치민화격발,효천조채용란청백단백치민화격발,간예조재채용란청백단백치민화격발전급여맹로사특관위.채용폐공능검측각조대서기도호기조력;채용매련면역흡부법(ELISA)대각조대서혈청중VEGF화백삼희D<4>(LTD4)진행정량분석;용면역조직화학방법검측VEGF、VEGF수체1(VEGFR1)급VEGFR:재대서폐조직내적표체수평.채용도상분석연건측정폐조직절편중적혈관계수、혈관평활기후도.결과 (1)폐공능검측현시효천조평균호기조력현저승고;(2)대조조혈청중VEGF화LTD4적수평분별위(17±5)ng/L화(6.1±0.7)ng/L,효천조분별위(31±6)ng/L화(10.7±3.5)ng/L,간예조분별위(15±4)ng/L화(9.8±1.6)ng/L,대조조화간예조분별여효천조비교차이유통계학의의(F치분별위63.78화39.56,균P<0.01);(3)면역조직화학결과현시효천조VEGF급수체균대량표체,이대조조화간예조유교소표체.(4)도상분석현시,대조조、효천조화간예조적혈관계수분별위14±2、22±2화16±4.(5)직선상관분석현시,혈관계수여혈청중VEGF적수평정상관(r=0.705,P<0.05).결론 VEGF급기수체재효천기도급폐내과도표체,삼여료기도염증화기도혈관중소적과정.맹로사특가능통과영향VEGF급기수체적표체영향기도염증화기도혈관중소적병리생리과정.
Objective To investigate the effect of montelukast(MK) on airway inflammation and remodeling in asthmatic rats, and to explore the regulating role of MK on vascular endothelial growth factor (VEGF) and its receptors. Methods Twenty-four male Sprague-Dawley rats were randomly divided into 3 groups, a control group(n =8), an asthmatic group(n =8) and a MK treated group(n =8). The rats were sensitized with ovalbumin and AL (OH3), and repeatedly exposed to aerosolized ovalbumin. Airway reactivity of the animals were measured by animal lung function meter. VEGF levels and leukotriene D4 (LTD4) in serum were measured by enzyme linked-immunosorbent assay(ELISA). The pathologic changes of bronchi and the lung tissue were evaluated, and the expression of VEGF and its receptors was analyzed with immunohistochemistry. The vascular counts and vascular smooth muscle thickness were measured by using image analysis system. Results The bronchial provocation test showed that, in the asthmatic group, the average expiratory resistance increased remarkably. The serum levels of VEGF and LTD4 in the asthmatic group were 31±6 and 11±4 respectively, significantly higher than those in the control group(17±5 and 6.1±0.7)respectively and in the MK group(15±4 and 9.8±1.6) respectively(F=63.78, 39.56, all P<0.01). Immunohistochemistry showed that, the expression of VEGF, VEGFR1 and VEGFR2 in the asthmatic group were increased, as compared to those in the control group and the treated group. The vascular counts were 14±2, 22±2 and 16±4 in the control, the asthmatic, and the treated groups. Conclusions VEGF and its receptors were over-expressed in the sensitized rat model, and involved in angiogenesis and airway remodeling. MK may be effective in reducing allergic airway inflammation and airway remodeling through VEGF and VEGFR.