内源性和外源性一氧化氮对正常和滴注博莱霉素大鼠肺泡巨噬细胞生存的调节(英文)  

Modulatory action of endogenous and exogenous nitric oxide on survival of alveolar macrophages from normal and bleomycin-treated rats

作　　者：陈晓玲[1] 黄善生[1] 刘昆[2] 艾洁[1] 

机构地区：[1]河北医科大学基础医学研究所病理生理研究室,石家庄050017 [2]河北医科大学 基础医学院生物化学教研室,石家庄050017

出　　处：《生理学报》2005年第5期619-626,共8页Acta Physiologica Sinica

基　　金：This work was supported by the Natural Science Foundation of Hebei Province(No.C2004000582)the Science Foundation for Doctor of Hebei Province(No.B2002215).

摘　　要：分别用一氧化氮(nitric oxide,NO)供体硝普钠(sodium nitroprusside,SNP)和前体L-精氨酸(L-arginin,L-Arg)孵育来自正 常大鼠(alveolar macrophages from normal rats,normal AMs)和滴注博莱霉素大鼠的肺泡巨噬细胞(alveolar macrophages from BLM-treated rats,BLM AMs),以探讨NO对不同状态细胞生存的调节。用凋亡和细胞周期评价细胞生存,细胞内Bcl-2 和Bax蛋白含量探讨其分子机制。结果如下:(1)BLM AMs的凋亡多于normal AMs;G0／G1期BLM AMs数少于normal AMs:S+G2M期BLM AMs数与相应的normal AMs数间的差异无统计学意义;(2)与normal AMs相比,BLM AMs内 Bcl-2下凋,Bax上调;(3)与相应的对照比,SNP和L-Arg能诱导normal AMs和BLM AMs凋亡;L-Arg仅能增加S+G2M 期BLM AMs数:(4)SNP和L-Arg诱导normal AMs内Bcl-2下调和Bax上调,但不能使BLM AMs内的Bcl-2和Bax发生 上述变化:(5)L-Arg下调BLM AMs内的Bax。上述结果显示:NO能诱导BLM AMs和normal AMs凋亡;Bcl-2和Bax 与NO诱导的normal AMs凋亡有关,而与NO诱导的BLM AMs的凋亡无关,提示NO诱导normal AMs和BLM AMs分 子机制不同;内源性NO促进BLM AMs增殖,这可能与其下调Bax有关。To investigate the modulatory action of endogenous and exogenous nitric oxide （NO） on survival of alveolar macrophages （AMs） in different cellular states, AMs from normal rats （normal AMs） and from bleomycin （BLM）-treated rats （BLM AMs） were incubated by sodium nitroprusside （SNP, NO donor） and L-arginin （L-Arg, NO precursor）, respectively. The survival of AMs was evaluated by apoptosis and cell cycles. The molecular mechanisms were investigated by the contents of Bcl-2, Bax proteins in AMs. The results are as follows： （1） The degree of BLM AMs apoptosis was higher than that of normal AMs; the number of BLM AMs in G0/G1 phases was less than that of normal AMs; there was no significant difference in S＋G2M phases between the number of BLM AMs and that of normal AMs. （2） Down-regulation of Bcl-2 and up-regulation of Bax occurred in BLM AMs, compared to those in normal AMs. （3） Apoptosis of AMs, either normal AMs or BLM AMs, was induced by both SNP and L-Arg, when compared to their respective control; only the number of BLM AMs in S＋G2M phases was increased by L-Arg. （4） SNP and L-Arg induced a down- regulation of Bcl-2 and an up-regulation of Bax proteins in normal AMs, but did not induce the same change pattern in BLM AMs. （5） The Bax in BLM AMs was down-regulated by L-Arg. It is concluded that NO can induce the apoptosis of BLM AMs and normal AMs; that Bcl-2 and Bax are implicated in NO-induced apoptosis of normal AMs, whereas they are not involved in that of BLM AMs, suggesting the differential molecular mechanisms underlying the NO-induced apoptosis of normal AMs and BLM AMs; and that endogenous NO promotes proliferation of BLM AMs, which might be associated with down-regulation of Bax.

关 键 词：一氧化氮 肺泡巨噬细胞 凋亡 细胞周期 肺纤维化 

分 类 号：R363[医药卫生—病理学]