国际呼吸杂志
國際呼吸雜誌
국제호흡잡지
INTERNATIONAL JOURNAL OF RESPIRATION
2008年
24期
1478-1481,封3
,共5页
宁方玉%王晓芝%王广丽%朱玉红%李彩玉
寧方玉%王曉芝%王廣麗%硃玉紅%李綵玉
저방옥%왕효지%왕엄려%주옥홍%리채옥
支气管哮喘%基质金属蛋白酶9%基质金属蛋白酶组织抑制因子1%糖皮质激素
支氣管哮喘%基質金屬蛋白酶9%基質金屬蛋白酶組織抑製因子1%糖皮質激素
지기관효천%기질금속단백매9%기질금속단백매조직억제인자1%당피질격소
Bronchial asthma%MMP-9%TIMP-1%Corticosteroid
目的 探讨基质金属蛋白酶(MMP)及基质金属蛋白酶组织抑制因子(TIMP)与支气管哮喘(简称哮喘)气道重塑的相关性以及预防性吸入激素对气道重塑的干预作用.方法 按随机数字表法将72只清洁级雄性Wistar大鼠分为对照组、哮喘组(卵原蛋白)、干预组(布地奈德+卵原蛋白),每组大鼠24只,分别于雾化激发后第7天、第28天和第35天处死每组大鼠中8只进行气道形态学观察,并采用病理图像分析系统测量大鼠的气道形态学参数.采用免疫组织化学测定肺组织MMP-9、TIMP-1的表达及ELISA方法 检测支气管肺泡灌洗液的上清中MMP-9及TIMP-1的含量.结果 ①与相应对照组相比,28d、35 d哮喘组内管壁厚度、平滑肌厚度、胶原沉积明显增厚(P<0.05或<0.01);经治疗后28 d、35 d组平滑肌厚度与相应哮喘组相比差异无统计学意义;而胶原沉积在治疗28 d、35 d组与相应哮喘组相比明显减少(P<0.01);内管壁厚度治疗35 d组与相应哮喘组相比差异开始下降,但仍高于对照组(P值均<0.05).②哮喘组支气管肺泡灌洗液中MMP-9及MMP-9/TIMP-1在初始阶段表达上调,在后期下降(P<0.01);TIMP-1在初始阶段表达上调,在后期亦有下降的趋势,但差异无统计学意义;应用糖皮质激素干预后,在早期MMP-9、TIMP-1及两者比值明显低于哮喘组(P<0.05),在晚期哮喘组与治疗组无明显差异.结论 哮喘发生、发展过程中,存在MMP-9/TIMP-1的表达失衡,糖皮质激素可能通过调节MMP-9/TIMP-1的平衡,阻抑胶原沉积而干预气道重塑的发生.
目的 探討基質金屬蛋白酶(MMP)及基質金屬蛋白酶組織抑製因子(TIMP)與支氣管哮喘(簡稱哮喘)氣道重塑的相關性以及預防性吸入激素對氣道重塑的榦預作用.方法 按隨機數字錶法將72隻清潔級雄性Wistar大鼠分為對照組、哮喘組(卵原蛋白)、榦預組(佈地奈德+卵原蛋白),每組大鼠24隻,分彆于霧化激髮後第7天、第28天和第35天處死每組大鼠中8隻進行氣道形態學觀察,併採用病理圖像分析繫統測量大鼠的氣道形態學參數.採用免疫組織化學測定肺組織MMP-9、TIMP-1的錶達及ELISA方法 檢測支氣管肺泡灌洗液的上清中MMP-9及TIMP-1的含量.結果 ①與相應對照組相比,28d、35 d哮喘組內管壁厚度、平滑肌厚度、膠原沉積明顯增厚(P<0.05或<0.01);經治療後28 d、35 d組平滑肌厚度與相應哮喘組相比差異無統計學意義;而膠原沉積在治療28 d、35 d組與相應哮喘組相比明顯減少(P<0.01);內管壁厚度治療35 d組與相應哮喘組相比差異開始下降,但仍高于對照組(P值均<0.05).②哮喘組支氣管肺泡灌洗液中MMP-9及MMP-9/TIMP-1在初始階段錶達上調,在後期下降(P<0.01);TIMP-1在初始階段錶達上調,在後期亦有下降的趨勢,但差異無統計學意義;應用糖皮質激素榦預後,在早期MMP-9、TIMP-1及兩者比值明顯低于哮喘組(P<0.05),在晚期哮喘組與治療組無明顯差異.結論 哮喘髮生、髮展過程中,存在MMP-9/TIMP-1的錶達失衡,糖皮質激素可能通過調節MMP-9/TIMP-1的平衡,阻抑膠原沉積而榦預氣道重塑的髮生.
목적 탐토기질금속단백매(MMP)급기질금속단백매조직억제인자(TIMP)여지기관효천(간칭효천)기도중소적상관성이급예방성흡입격소대기도중소적간예작용.방법 안수궤수자표법장72지청길급웅성Wistar대서분위대조조、효천조(란원단백)、간예조(포지내덕+란원단백),매조대서24지,분별우무화격발후제7천、제28천화제35천처사매조대서중8지진행기도형태학관찰,병채용병리도상분석계통측량대서적기도형태학삼수.채용면역조직화학측정폐조직MMP-9、TIMP-1적표체급ELISA방법 검측지기관폐포관세액적상청중MMP-9급TIMP-1적함량.결과 ①여상응대조조상비,28d、35 d효천조내관벽후도、평활기후도、효원침적명현증후(P<0.05혹<0.01);경치료후28 d、35 d조평활기후도여상응효천조상비차이무통계학의의;이효원침적재치료28 d、35 d조여상응효천조상비명현감소(P<0.01);내관벽후도치료35 d조여상응효천조상비차이개시하강,단잉고우대조조(P치균<0.05).②효천조지기관폐포관세액중MMP-9급MMP-9/TIMP-1재초시계단표체상조,재후기하강(P<0.01);TIMP-1재초시계단표체상조,재후기역유하강적추세,단차이무통계학의의;응용당피질격소간예후,재조기MMP-9、TIMP-1급량자비치명현저우효천조(P<0.05),재만기효천조여치료조무명현차이.결론 효천발생、발전과정중,존재MMP-9/TIMP-1적표체실형,당피질격소가능통과조절MMP-9/TIMP-1적평형,조억효원침적이간예기도중소적발생.
Objective To investigate the correlations between MMP,TIMP and airway remodeling in brochial asthma(asthma),and the effect of preventive inhaling budesonide(BUD)on airway remodeling.Methods Seventy-two Wistar rats were divided into control group,asthmatic group(sensitized by OVA)and steroids treated group(treated by steroid and sensitized by OVA),each group had 24 rats.The subjects were observed at 3 phases:7 days,28 days,35 days after activation.General histological changes were
observed using HE and Masson trichrome stained sections.The parameter of the internal perimeter(Pi),bronchial smooth muscle area(Wam),internal wall area(Wai),and Wc01 collage deposition(Wcol)of the airway were measured by computer-assisted image analysis system.The protein expressions of MMP-9 and TIMP-1 in lung tissue were examined by immunohistochemical analysis and the concentrations of MMP-9 and TIMP-1 in the blood and BALF were quantified by ELISA.Results ①The Wai/Pi,Wam/Pi and Wcol/Pi of asthmatic group in 28 days and 35 days were significantly higher than those of control group(P<0.05 or P<0.01);After treatment with BUD the Wam/Pi of 28 days and 35 days BUD treated group had no significant diference with that of corresponding asthmatic group;but the Wcol/Pi of 28 days and 35 days BUD treated group decreased obviously compared with that of asthmatic group(P<0.01).The Wai/Pi of 35 days BUD treated group was significantly lower than that of the 35 days asthmatic group(P<0.05),but was significantly higher than the 35 days control group(P<0.05).②MMP-9 and MMP-9/TIMP-1 increased at the time point of 7 days.but it decreased in the late stage(35 days)of airway remodeling in asthmatic group.And the level of TIMP-1 increased at the time point of 7 days and had a downward trend at the time point of 35 days.After treatment with BUD,MMP-9,TIMP-1 and MMP-9/TIMP-1 increased at the time point of 7 days.but there was no statistic significance between asthmatic group and BUD group in the late stage(35 days).Conclusions The inbalance of MMP-9/TIMP-1 ratios may exist in the progress of asthma.Regulating the balance between MMP-9 and TIMP-1 by steroids may be one of the mechanisms by which airway inflammation and remodeling are inhibited in asthma.