CAJ | 학술논문

目的: 观察单纯高碳酸血症大鼠模型的血清中性粒细胞蛋白酶(NE)、基质金属蛋白酶-2 (MMP-2)、基质金属蛋白酶-9(MMP-9 )和金属蛋白酶组织抑制剂(TIMP-1)的活性,以及它们在肺组织中的表达,探讨高浓度二氧化碳(CO_2)引起肺组织损伤的机制.方法: 雄性Wistar大鼠40只,随机分为正常对照组(A组, 20只大鼠)、高碳酸血症组(B组,20只大鼠).B组大鼠置于高CO_2舱中,并向舱中匀速输入6% CO_2 混合气体(6% CO_2,21% O_2,73% N_2),每天7 h,连续4周,完成大鼠高碳酸血症模型的复制.用ELISA法测定大鼠血清MMP-2、MMP-9、TIMP-1活性及NE活性;弹力纤维染色标本进行弹性纤维相对含量的测定;免疫组化方法检测肺组织中MMP-2、MMP-9及 TIMP-1的表达及光镜下进行病理学观察.结果: B组大鼠血清MMP-2、MMP-9、TIMP-1活性与A组之间并无显著差异(P>0.05);B组大鼠NE活性明显高于A组(P<0.01);光镜下可见B组大鼠肺泡壁明显增厚,肺微血管内皮细胞损伤,小静脉扩张,血栓形成;小动脉内皮细胞肿胀,管腔狭窄,血管周围有袖套状水肿区;并可见小灶性肺实质出血;A组大鼠弹力纤维呈束状,连续无断裂;B组大鼠可见弹力纤维断裂降解,且肺组织中弹力纤维的含量较A组明显减少(P<0.01);B组大鼠肺组织中MMP-2的表达明显低于A组(P<0.01);而肺组织中MMP-9及TIMP-1的表达B组大鼠明显高于A组(P<0.01).结论: 通过复制出常压、常氧、单纯高碳酸血症动物模型;单纯的PaCO_2增高对肺动脉压无明显影响;高浓度CO_2可以使NE活性明显增高,使弹性蛋白的降解增多,肺组织弹性纤维断裂降解,数量减少;在单纯高碳酸血症动物模型中,MMP-2的表达明显降低,MMP -9及 TIMP-1在肺组织中表达明显增高,导致肺损伤.
목적: 관찰단순고탄산혈증대서모형적혈청중성립세포단백매(NE)、기질금속단백매-2 (MMP-2)、기질금속단백매-9(MMP-9 )화금속단백매조직억제제(TIMP-1)적활성,이급타문재폐조직중적표체,탐토고농도이양화탄(CO_2)인기폐조직손상적궤제.방법: 웅성Wistar대서40지,수궤분위정상대조조(A조, 20지대서)、 고탄산혈증조(B조,20지대서).B조대서치우고CO_2창중,병향창중균속수입6% CO_2 혼합기체(6% CO_2,21% O_2,73% N_2),매천7 h,련속4주,완성대서고탄산혈증모형적복제.용ELISA법측정대서혈청MMP-2、MMP-9、TIMP-1활성급NE활성;탄력섬유염색표본진행탄성섬유상대함량적측정;면역조화방법검측폐조직중MMP-2、MMP-9급 TIMP-1적표체급광경하진행병이학관찰.결과: B조대서혈청MMP-2、MMP-9、TIMP-1활성여A조지간병무현저차이(P>0.05);B조대서NE활성명현고우A조(P<0.01);광경하가견B조대서폐포벽명현증후,폐미혈관내피세포손상,소정맥확장,혈전형성;소동맥내피세포종창,관강협착,혈관주위유수투상수종구;병가견소조성폐실질출혈;A조대서탄력섬유정속상,련속무단렬;B조대서가견탄력섬유단렬강해,차폐조직중탄력섬유적함량교A조명현감소(P<0.01);B조대서폐조직중MMP-2적표체명현저우A조(P<0.01);이폐조직중MMP-9급TIMP-1적표체B조대서명현고우A조(P<0.01).결론: 통과복제출상압、상양、단순고탄산혈증동물모형;단순적PaCO_2증고대폐동맥압무명현영향;고농도CO_2가이사NE활성명현증고,사탄성단백적강해증다,폐조직탄성섬유단렬강해,수량감소;재단순고탄산혈증동물모형중,MMP-2적표체명현강저,MMP -9급 TIMP-1재폐조직중표체명현증고,도치폐손상.
AIM:To study the expression of matrix metalloproteinase-9(MMP-9),matrix metalloproteinase-2(MMP-2) and the tissue inhibitor of metalloproteinase(TIMP-1) in the lung tissue of the hypercapnia rat.METHODS:Forty Wistar rats were randomly divided into a control group (group A,n=20) and hypercapnia group (group B,n=20). Group B received mix gas exposure (6% CO_2,21% O_2,72% N_2) 7 h daily for 4 weeks. The parameters we would examine were as follow:arterial blood gas;the mean pulmonary artery pressure;MMP-2,MMP-9,TIMP-1,and NE activity in lung tissue. Masson pigmentation of elasticity fibre was analyzed by computer image analyzer. Histopathological changes of lung tissue were observed under light microscope. The protein expression of MMP (MMP-2,MMP-9) and TIMP (TIMP-1) in lung tissue were determined by immunocytochemistry.RESULTS:Decompensate respiratory acidosis (pH=7.20±0.04,PaCO_2=7.84±0.15) developed in group B. The mean pulmonary artery pressure were similar between groups B and A (P>0.05). Tissue edema in the lung,endothelial cell damage of the small blood vessels,pulmonary micro thrombus formations and increased pulmonary capillary permeability were observed in group B. NE activity increased significantly (P<0.01). However,no significant change of MMP-2,MMP-9,TIMP-1 activity was found in group B and group A (P>0.05). There was significant decrease in the relative content of elasticity fibre in lung tissue in group B compared to group A (P<0.01). The expression of MMP-2 protein in the lung tissue of group B was lower than that in group A (P<0.01),but the expression of both MMP-9 and TIMP-1 proteins in the lung tissue in group B were higher than those in group A (P<0.01).CONCLUSION:Hypercapnia rat model is successfully reproduced by exposure of animals to the mix gas exposure (6% CO_2,21% O_2,and 72% N_2). The pulmonary artery pressure is not affected by hypercapnia. High concentration of CO_2 causes increase of NE activity and decrease in the relative content of elasticity fibre. High concentration of CO_2 causes the increase of MMP-2 protein expression and decrease in the MMP-9 and TIMP-1 protein expression.