摘要
目的 观察一氧化氮 (NO)对哮喘大鼠基质金属蛋白酶 (MMP)及金属蛋白酶组织抑制物表达的影响 ,探讨其在哮喘气道结构重建中的作用。方法 30只雄性Wistar大鼠随机分为对照组、哮喘组和左旋精氨酸组 (L Arg组 ) ,每组 1 0只。肺组织作病理切片并HE染色 ,通过病理图像分析系统测定支气管基底膜周径 (Pbm)、总管壁面积 (WAt)、内壁面积 (WAi) ,平滑肌面积 (WAm)等形态学参数。用NO与一氧化氮合酶 (NOS)试剂盒测定肺组织中亚硝酸盐 /硝酸盐 (NO- 2 /NO- 3)水平与NOS活性。半定量逆转录聚合酶链反应技术 (RT PCR)分析肺组织中MMP 2与TIMP 1mRNA的表达。结果(1 )WAt/Pbm、WAi/Pbm及WAm/Pbm哮喘组 [分别为 (2 5 3± 2 1 ) μm2 / μm、(2 0 4± 2 3) μm2 / μm、(4 2±2 0 ) μm2 / μm]和L Arg组 [分别为 (35 1± 2 6) μm2 / μm、(2 5 3± 2 0 ) μm2 / μm、(8 7± 1 5) μm2 / μm]与对照组 [分别为 (2 0 8± 1 3) μm2 / μm、(1 5 3± 2 1 ) μm2 / μm、(3 1± 1 1 ) μm2 / μm]比较 ,差异有显著性(P <0 0 1 ) ;L Arg组与哮喘组比较差异亦有显著性 (P <0 0 5)。 (2 )肺组织中NO- 2 /NO- 3水平哮喘组[(7 2± 2 1 )nmol/mg]和L Arg组 [(1 1 8± 1 7)nmol/mg]与对照组 [(3 1± 1 2 )
Objective To observe the effect of nitric oxide on expression of matrix metalloproteinase and tissue inhibitor of metalloproteinase in asthmatic rats Methods Thirty healthy male Wistar rats were randomly divided into control ( n =10), asthmatic ( n =10) and L arginine ( n =10) groups. Lung tissues were sliced and stained with HE The following morphometric parameters were measured by image analysis system: airway wall basement membrane perimeter (Pbm), total bronchial wall area (WAt), the inner wall area (WAi) and the area of smooth muscle (WAm) Levels of nitrites/nitrates and NOS activity in the lungs were measured by commercial NO and NOS kits Transcriptional levels of MMP 2 and TIMP 1 mRNA in the lungs were assessed by semiquantitative reverse transcription polymerase chain reaction (RT PCR). Results (1) WAt/Pbm, WAi/Pbm and WAm/Pbm in the L arginine group were(35 1±2 6) μm 2/μm, (25 3±2 0) μm 2/μm, and (8 7±1 5) μm 2/μm, respectively WAt/Pbm, WAi/Pbm and WAm/Pbm in the asthmatic group were (25 3±2 1) μm 2/μm, (20 4±2 3) μm 2/μm,and (4 2±2 0) μm 2/μm, respectively WAt/Pbm, WAi/Pbm and WAm/Pbm in the control group were (20 8±1 3) μm 2/μm,(15 3±2 1) μm 2/μm,and (3 1±1 1) μm 2/μm , respectively The differences among three groups were statistically significant (2) Levels of nitrites/nitrates in the L arginine group [(11 8±1 7) nmol/mg] and the asthmatic group [(7 2±2 1) nmol/mg] were significantly higher than that in the control group [(3 1±1 2) nmol/mg] NOS activity in the lungs was (16 5±1 3) U/mg L arginine group , (10 8 ±1 4) U/mg asthmatic group, and (1 46±0 98) U/mg control group, respectively, the differences being statistically significant between groups. (3) MMP 2 and TIMP 1 mRNA levels in the L arginine group and the asthmatic group were significantly higher than that in the control group [L arginine group (0 82±0 11), (0 51±0 12); asthmatic group(0 68±0 14), (0 56±0 10); control group (0 14±0 03), (0 11±0 05), respectively] The difference in the MMP 2 mRNA levels was significant between the L arginine group and the asthmatic group ( P <0 05), but the difference in the TIMP 1 mRNA levels between the two groups was not statistically significant ( P >0 05) (4) A significant positive correlation was found between the MMP 2 mRNA levels and nitrites/nitrates levels in L arginine group and asthmatic group ( r s =0 65, 0 68, P <0 05), but there was no significant correlation between the nitrites/nitrates levels and the TIMP 1 mRNA levels in the two groups ( r s =0 23, 0 18, P >0 05) Conclusion Nitric oxide may contribute to airway inflammation and remodeling by influencing the balance between matrix metalloproteinases and tissue inhibitors of metalloproteinases
出处
《中华结核和呼吸杂志》
CAS
CSCD
北大核心
2002年第5期276-279,共4页
Chinese Journal of Tuberculosis and Respiratory Diseases
基金
国家自然科学基金项目 ( 39770 34 0 )
