L-精氨酸对哮喘大鼠气道平滑肌细胞增殖的影响

目的 观察L-精氨酸（L-Arg）对哮喘气道重构大鼠气道平滑肌细胞（ASMC）的细胞周期分布及细胞周期调节蛋白（CCRP）表达水平的影响，探讨L-Arg体内干预哮喘大鼠ASMC增殖的可能作用机制。方法实验分成对照组、哮喘组、L-Arg组，建立大鼠哮喘气道重构模型，检测血清NO2^-／NO3^-含量、肺内支气管内管壁和平滑肌层厚度及ASMC核数、ASMC的细胞周期分布以及ASMC内细胞周期素E（cyclin E）、cyclinA、cyclinB、蛋白27^kip1（P27^kip1）的表达。结果 哮喘组大鼠支气管内管壁、平滑肌层的厚度和ASMC数目显著大于对照组（P〈0．05）；L-Arg组大鼠支气管内管壁的厚度、平滑肌层的厚度和ASMC数目显著小于哮喘组（P〈0．05）。哮喘组血清一氧化氮（nitricoxide，NO）水平显著低于对照组（P〈0．05）；L-Arg组血清NO水平显著高于哮喘组（P〈0．01）。哮喘组G0／G1期ASMC比例及P27^kip1表达水平显著低于对照组（P〈0．01），G2／M＋S期ASMC比例及cyclinE、cyclinA和cyclinB表达水平显著高于对照组（P〈0．01）；L-Arg组G0／G1期ASMC比例及P27^kip1表达水平显著高于哮喘组（P〈0．05），G2／M＋S期ASMC比例及cyclinE和cyclinA表达水平显著低于哮喘组（P〈0．05）。结论 L-Arg通过调控CCRP的表达水平阻滞细胞从G1期进入S期而抑制哮喘ASMC的增殖。

Influence of L-arginine on proliferation of airway smooth muscle cells in asthmatic rats

Objective To investigate the influence of L-arginine(L-Arg) on the cell cycle distribution and the expression of cell cycle regulatory proteins(CCRP) in the proliferation of airway smooth muscle cell (ASMC) in asthmatic rats.Methods The rats were randomly divided into three groups: control group,asthmatic group and L-Arg group.The concentration of NO-2/NO-3 in serum,the thickness of inner airway wall and smooth muscle layer,the number of ASMC nucleus,the cell cycle distribution and the expression of cyclin E,cyclin A,cyclin B and P27kip1in ASMC were measured.Results The thickness of inner airway wall,smooth muscle layer and the number of ASMC nucleus in the rats of asthmatic group were much larger than those in control group (P<0.05); the thickness of inner airway wall,smooth muscle layer and the number of ASMC nucleus in rats of L-Arg group were much smaller than those in asthmatic group (P<0.05).The levels of serum NO were obviously lower in the rats of asthmatic group than those in L-Arg group(P<0.05),however the levels of serum NO were significantly higher in the rats of L-Arg group than those in control group(P<0.01).The percentage of ASMC in G0/G1 phase and the expression of P27kip1of ASMC in asthmatic group were significantly higher than those in control group(P<0.01),however the percentage of ASMC in G2/M+S phase and the expression of cyclin E,cyclin A,cyclin B of ASMC in asthmatic group were significantly lower than those in control group(P<0.01);the percentage of ASMC in G0/G1 phase and the expression of P27kip1of ASMC in L-Arg group were significantly higher than that in asthmatic group(P<0.05),the percentage of ASMC in G2/M+S phase and the expression of cyclin E,cyclin A of ASMC in L-Arg group were significantly lower than that in asthmatic group(P<0.05).Conclusions L-Arg may restrain proliferation of ASMC in asthmatic rats by means of preventing the cell cycle course from G1 phase into S phase by regulating CCRP expression.