不同剂量的一氧化氮对福尔马林炎性痛大鼠脊髓背角Bcl-2/Bax表达的影响  

Effect of nitric oxide with different doses on Bcl-2/Bax in spinal dorsal horn in rats induced by formalin

作　　者：未小明[1] 李宽 祁文秀[3] 

机构地区：[1]山西医科大学,太原030001 [2]国家康复辅具研究中心附属康复医院,北京100176 [3]山西医科大学汾阳学院生理学教研室,汾阳032200

出　　处：《神经解剖学杂志》2011年第1期77-81,共5页Chinese Journal of Neuroanatomy

摘　　要：目的:探讨多次应用不同剂量的一氧化氮(NO)对福尔马林炎性痛中脊髓背角神经元Bcl-2、Bax表达的影响。方法:连续4 d给大鼠各进行鞘内注射不同剂量的一氧化氮前体左旋精氨酸(L-arginine,L-Arg)10μg/d(低L-Arg组)、250μg/d(高L-Arg组)或一氧化氮合酶(nitric oxide synthase,NOS)抑制剂Nω-硝基-L-精氨酸甲酯(Nω-nitro-L-arginine methylester,L-NAME)2700μg/d(L-NAME组),鞘内注射生理盐水(NS组)作为对照,各给药1次/d。随后于大鼠右后肢脚掌皮下注射福尔马林(2%,100μl),4 h后分别做免疫组化和Western Blot检测脊髓背角Bcl-2和Bax蛋白的表达。结果:免疫组化结果显示,Bcl-2和Bax表达分布于两侧脊髓背角,但主要位于脊髓背角浅层,各组在注射福尔马林同侧均明显高于对侧。Western Blot结果显示Bcl-2和Bax蛋白表达含量的比值,在各实验组与对照组比较,低L-Arg组Bcl-2/Bax比值明显升高,而高L-Arg组和L-NAME组Bcl-2/Bax比值均明显降低。bcl-2为抑制细胞凋亡的基因,而bax为促进细胞凋亡的基因。结论:在炎性痛模型中,低剂量的NO以促进抑凋亡基因的表达为主,而高剂量的NO以及NO生成不足均以促进促凋亡基因的表达为主,进而影响炎性痛的发生。Objective：To investigate the effects of multiple application of different doses of nitric oxide（NO） on Bcl-2/Bax in spinal dorsal horn induced by formalin.Methods：A succession of 4 d intrathecal injection of NO precursor L-arginine（L-Arg）10 μg/d（low L-Arg group） or 250 μg/d（high L-Arg group） or NOS inhibitor Nω-nitro-L-arginine methylester（L-NAME） 2700 μg/d（L-NAME group） in rats,and normal saline（NS group） was applied as a control,and administration once a day.Then rats were subcutaneously injected formalin（2%,100 μL） into the right hindpaw,four hours later after formalin injection,Bcl-2 or Bax protein expression were detected with immunocytochemistry and Western Blot.Results：The immunocytochemistry showed the distributions of Bcl-2 and Bax were in both sides of the dorsal horn,especially in superficial laminae,and the expressions of bcl-2 and bax in the ipsilateral side of formalin injection were significantly increased than that in contralateral side of formalin injection in all four groups;the ratio of Bcl-2/Bax with Western-Blot was increased in low L-Arg group compared with normal saline group and was all decreased in high L-Arg group or L-NAME group compared with normal saline group.bcl-2 and bax are two major genes in the regulation of apoptosis,bcl-2 inhibits apoptosis and bax promotes apoptosis.Conclusion：Therefore,in inflammatory pain model,low doses of NO can promote the antiapoptotic gene expression,while high doses of NO and insufficient of NO both can promote pro-apoptotic gene expression,which affect the incidence of inflammatory pain.

关 键 词：左旋精氨酸 Nω-硝基-L-精氨酸甲酯 一氧化氮 福尔马林试验 Bcl-2 BAX 凋亡 

分 类 号：R363[医药卫生—病理学]