大鼠急性肺损伤时iNOS mRNA和eNOS mRNA表达的时相变化

Chronological Changes of iNOS mRNA and eNOS mRNA Expression in Rats' Acutely Injured Lungs

目的 :观察内毒素性急性肺损伤时肺组织中一氧化氮 (NO)和一氧化氮合酶mRNA的时相变化 ,并探讨其相互关系。方法 :用内毒素 (LPS)复制急性肺损伤模型 ,分别测定 0 .5 ,1,2 ,3,4h各组肺组织NO和丙二醛 (MDA)的含量 ;用原位杂交方法检测各组大鼠肺组织中诱导型一氧化氮合酶mRNA(iNOSmRNA)和内皮型一氧化氮合酶mRNA(eNOSmRNA)的表达水平。结果 :大鼠给予LPS后 ,①肺组织MDA含量随时间延长而逐渐增加 ,不同时点的均值互有差异 (P <0 .0 5 ) ,并且均显著高于正常对照组 (P <0 .0 5 ) ;②各时点肺组织NO含量和iNOSmRNA表达量均显著大于正常对照组 (P <0 .0 5 ) ,并且均在 2h时达到高峰 ,以后呈下降趋势。二者的变化呈显著正相关 (P <0 .0 1) ;③ 2h前 (含 2h)肺组织MDA含量随iNOSmRNA表达增加所致的NO产量增多而增加 ,2h后二者变化趋势相反 ;④各时点肺组织eNOSmRNA表达量与正常对照组比差异均无显著性。结论 :内毒素性急性肺损伤时 ,肺组织iNOSmRNA大量表达 ,导致内源性NO爆发式产生 ,从而介导肺损伤。NO产量在静注内毒素后 2h达到高峰 ,以后呈下降趋势。

Objective: To investigate the temporal changes of NO and NOSmRNA in the lung during acute endotoxic lung injury and their interrelation. Methods: The acute lung injury model with endotoxin was duplicated, and then the content of NO and MDA in lung at 0.5 h, 1 h, 2 h, 3 h,and 4 h was respectively measured. The expression of iNOS mRNA and eNOS mRNA in the lung was accordingly detected through in situ blotting. Results: After treatment with LPS. ① the content of MDA increased as the time processed, and there was difference in the average value among the groups; ② the NO and iNOS mRNA level of model groups increased remarkably compared with that of the normal group(P<0.05), which reach the peak at 2 h. They were highly correlated(P<0.01); ③ During the first two hours,the content of MDA increased with NO resulting from the enhanced level of iNOSmRNA; ④ The level of eNOS mRNA in the model groups had no significant difference compared with that of the normal group. Conclusion: In the endotoxic acute lung injury, alarge amount of iNOS mRNA is expressed in the lung, which causes the outbreak of endogenic NO, and which subsequently mediates lung injury. The production of NO reach a peak two hours after the injection of endotoxin, then it begins to decrease.