大鼠肺纤维化形成中内源性一氧化氮对肺泡上皮细胞凋亡的影响

Role of endogenous nitric oxide in apoptosis of alveolar epithelial cells in the development of pulmonary fibrosis in rats

目的研究大鼠肺纤维化形成过程中异常增多的肺内源性一氧化氮对肺泡上皮细胞凋亡的影响。方法气管内滴注博莱霉素,用硝酸还原法检测出肺血NO2-/NO3-含量;TdT介导的dUTP缺口末端标记法(TUNEL)和透射电镜观察肺泡上皮细胞凋亡。分别观察注BLMA5后14d和30d以及用氨基胍(AG)阻断iNOS合成NO后上述指标的变化。结果(1)注BLMA5后14d,出肺血NO2-/NO3-含量分别高于正常对照组和注BLMA5后30d组(均P<001);凋亡的肺泡上皮细胞数亦分别多于正常对照和注BLMA5后30d组(均P<001)。(2)AG阻止出肺血NO2-/NO3-含量增高的同时,亦抑制了肺泡上皮细胞的凋亡。结论在肺纤维化形成过程中,内源性NO的增多,有诱导肺泡上皮细胞凋亡的作用。

AIM: To study the role of high level of endogenous nitric oxide (NO) in apoptosis of alveolar epithelial cells in the development of pulmonary fibrosis in rats. METHODS: The content of nitrite/nitrate (NO 2-/NO 3-) in out-flowing pulmonary blood (OPB) was assayed by nitric acid reduction method. The apoptosis of alveolar epithelial cells was observed by TdT-mediated dUTP nick-end labeling (TUNEL) and electron microscopy, respectively. The above indices were observed on the day 14 and the day 30 after intratracheal administration of BLMA 5 alone or along with blockade of iNOS by aminoguanidine (AG) in rats. RESULTS: (1) Both the content of NO 2-/NO 3- in OPB and the number of apoptotic alveolar epithelial cells in lung were increased in BLMA 5 14 d group, compared with normal control group and BLMA 5 30 d group, respectively (P<0.05). The high level of NO 2-/NO 3-in OPB and the apoptosis of alveolar epithelial cells were ameliorated by AG. CONCLUSION: The apoptosis of alveolar epithelial cell is induced by high level of endogenous NO in the development of pulmonary fibrosis. [