哮喘豚鼠气道重构中基质金属蛋白酶9及抑制物TIMP1的表达
哮喘;气道重构;明胶酶B;金属蛋白酶1组织抑制剂,,哮喘;气道重构;明胶酶B;金属蛋白酶1组织抑制剂,【摘要】,【关键词】,1材料
WANG GuangHui1, JIN FaGuang1, CHU DongLing1, DUAN Li21Department of Respiratory Diseases, Tangdu Hospital, Xian 710038, China, 2Institute of Neurosciences, School of Basic Medicine, Fourth Military Medical University, Xian 710033, China
【Abstract】 AIM: To investigate the roles of matrix metalloproteinase9 (MMP9) and tissue inhibitor of metalloproteinase1 (TIMP1) in airway remodeling of asthmaric guinea pigs. METHODS: Guinea pigs were sensitized with ovalbumin conjuncted with Al(OH)3, and subsequently challenged repeatedly with ovalbumin aerosol. The guinea pigs were randomly divided into the control group,asthmatic 4, 6, 8week groups. The expressions of MMP9 and TIMP1 in bronchi and lung tissues were observed by immunohistochemistry combined with the microimage analysis.The levels of MMP9 mRNA and TIMP1 mRNA were determined by semiquantitative PCR. RESULTS: ① After repeated allergen challenge, smooth muscle hyperplasia was obvious in guinea pig bronchi.Expression levels of MMP9 and TIMP1 in the epithelial cells of bronchi were significantly higher in asthmatic animals than those of control group. ② The expression of MMP9 in asthmatic guinea pigs lung tissues was 0.52±0.05 in 4week group, 0.74±0.05 in 6week group, 0.48±0.04 in 8week group , 0.21±0.04 in control group (P<0.05). The expression of TIMP1 in asthmatic guinea pigs lung tissues was 0.36±0.04 in 4week group,0.83±0.05 in 6week group, 0.97±0.05 in 8week group , 0.20±0.02 in control group (P<0.05). ③ The results of immunocytochemistry were consistent with those of RTPCR. ④ The upregulation of MMP9 expression become slower than TIMP1 since the 4th week in asthmatic animals. So ratio of MMP9/ TIMP1 was decreased. CONCLUSION: The expression levels of MMP9 and TIMP1 were closely correlated with asthma airway remodeling, and the ratio of MMP9/ TIMP1 may reflecte the degree of asthma airway remodeling. ......
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