文章摘要
金海燕,廖成俊,包雪鹦,等.清脑止痛胶囊对偏头痛大鼠核因子 -κB/诱导型一氧化氮合酶 /环氧化酶 2信号通路及痛觉敏感性的影响[J].安徽医药,2021,25(4):825-829.
清脑止痛胶囊对偏头痛大鼠核因子 -κB/诱导型一氧化氮合酶 /环氧化酶 2信号通路及痛觉敏感性的影响
Effects of Qingnaozhitong capsules on NF-κB/iNOS/COX2 signal pathway and pain sensitivity in migraine rats
  
DOI:10.3969/j.issn.1009-6469.2021.04.047
中文关键词: 偏头痛  中草药  清脑止痛胶囊  痛觉敏感性  核因子 -κB/诱导型一氧化氮合酶 /环氧化酶 2信号通路(NFκB/iNOS/COX2)
英文关键词: Migraine disorders  Drugs, Chinese Herbal  Qingnaozhitong capsules  Pain sensitivity  Nuclear factor-κB/inducible nitric oxide synthase/cyclooxygenase 2 signaling pathway
基金项目:吉林省科技厅科研基金资助课题(20140310001YY)
作者单位E-mail
金海燕 深圳市龙岗区第三人民医院神经内科广东深圳518000  
廖成俊 深圳市龙岗区第三人民医院神经内科广东深圳518000  
包雪鹦 解放军九六四医院神经内科吉林长春 130000  
李冕动 深圳市龙岗区第三人民医院神经内科广东深圳518000  
赖金玉 深圳市龙岗区第三人民医院神经内科广东深圳518000  
张惠光 深圳市龙岗区第三人民医院神经内科广东深圳518000 yan-jin-111@163.com 
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中文摘要:
      目的探究清脑止痛胶囊(QNZTJN)对偏头痛大鼠核因子 -κB/诱导型一氧化氮合酶 /环氧化酶 2(NF-κB/iNOS/COX2)信号通路及痛觉敏感性的影响。方法吉林大学实验动物中心提供的健康雄性 SPF级 Wistar大鼠随机分为 6组:空白组(NC组)、模型组(M组)、阳性药物正天丸组(ZTW组)、 QNZTJN低(QNZTJN-L组)、中(QNZTJN-M组)、高(QNZTJN-H组)剂量组。给药 7d后,皮下注射硝酸甘油复制大鼠偏头痛模型,观察造模后大鼠行为学反应及痛觉阈值变化,大鼠脑组织中一氧化氮(NO)、 5-羟色胺(5-HT)表达水平及 NF-κB p65、iNOS、COX2蛋白表达量。研究起止时间 2019年 2—6月。结果与 NC组比较, M组、 ZTW组、 QNZTJN-L组、 QNZTJN-M组、 QNZTJN-H组大鼠行为学评分、痛觉阈值、脑组织 NO含量[(3.97±0.48)mol/L(1.83±0.27)mol/L(2.91±0.25)mol/L(1.85±0.18)mol/L(1.79±0.22)mol/L比(1.42±0.21)mol/L]、 NF-κB p65[(0.87±0.15)(0.21± 0.04)(0.76±0.09)(0.14±0.03)(0.15±0.04)比(0.12±0.02)]、 iNOS[(0.62±0.07)(0.19±0.02)(0.54±0.06)(0.16±0.03)(0.16±0.04)比(0.14±0.02)]、 COX2蛋白表达量[(0.65±0.08)(0.21±0.04)(0.52±0.07)(0.17±0.03)(0.17±0.04)比(0.15±0.03)]增加(P<0.05)脑组织 5-HT含量[(3.12±0.69)ng/mg(4.73±0.76)ng/mg(3.95±0.71)ng/mg(4.81±0.82)ng/mg(4.86±0.84)ng/mg比(5.84±0.95)ng/mg],降低(P<0.05);与 M组比较, ZTW组、 QNZTJN-L、QNZTJN-M组、 QNZTJN-H组大鼠行为学评分、痛觉阈值、脑组织 NO含量、 NFκB p65、iNOS、COX2蛋白表达量降低(P<0.05),脑组织 5-HT含量升高(P<0.05),其中 QNZTJN-M组、 QNZTJN-H组上述各指标均优于 QNZTJN-L组(P<0.05),而 QNZTJN-M组与 QNZTJN-H组比较差异无统计学意义(P>0.05)。结论 QNZTJN可降低 NO水平、升高 5-HT水平,缓解偏头痛大鼠行为学症状,升高其痛觉阈值,并在一定剂量范围内呈剂量依赖性,可能是通过抑制 NFκB/iNOS/COX2信号通路激活实现的。
英文摘要:
      Objective To investigate the effects of Qingnaozhitong capsules (QNZT) on nuclear factor-κB/inducible nitric oxide synthase/cyclooxygenase 2 (NF-κB/iNOS/COX2) signal pathway and pain sensitivity in migraine rats.Methods Healthy male SPF Wistarrats provided by experimental animal Center of Jilin University were randomly assigned into 6 groups: blank group (NC group), modelgroup (M group), positive drug Zhengtian pill group (ZTW group), low (QNZT-L group), medium (QNZT-M group), high (QNZT-H group) dose QNZT groups. Seven days after administration, the migraine model was established by subcutaneous injection of nitroglycerin, the changes of behavioral response and pain threshold, the expressions of nitric oxide (NO) and 5-hydroxyserotonin (5-HT) and the NF-κB p65, iNOS and COX 2 protein expressions were observed. The study was carried out from February 2019 to June 2019.Results Compared with NC group, the behavioral score, the pain threshold, the contents of NO in brain tissue [(3.97±0.48)mol/L,(1.83±0.27)mol/L, (2.91±0.25)mol/L, (1.85±0.18)mol/L, (1.79±0.22)mol/L vs (1.42±0.21)mol/L], the protein expressions of NF-κB p65 [(0.87± 0.15), (0.21±0.04), (0.76±0.09), (0.14±0.03), (0.15±0.04) vs (0.12±0.02)], iNOS [(0.62±0.07), (0.19±0.02), (0.54±0.06), (0.16±0.03), (0.16±0.04) vs (0.14±0.02)] and COX2 [(0.65±0.08), (0.21±0.04),(0.52±0.07),(0.17±0.03), (0.17±0.04) vs (0.15±0.03)] of rats in M group, ZTW group, QNZT-L, QNZT-M and QNZT-H groups increased (P<0.05), and the contents of 5-HT [(3.12±0.69)ng/mg,(4.73± 0.76)ng/mg, (3.95±0.71)ng/mg, (4.81±0.82)ng/mg, (4.86±0.84)ng/mg vs (5.84±0.95)ng/mg]in brain tissue decreased(P<0.05). Comparedwith M group, the behavioral score, the pain threshold, the content of NO in brain tissue, the protein expressions of NF-κB p65, iNOS and COX2 of the rats in ZTW group, QNZT-L, QNZT-M and QNZT-H groups decreased (P<0.05), while the content of 5-HT in brain tissue increased (P<0.05). The above indexes of QNZT-M and QNZT-H group were better than those of QNZT-L group (P<0.05), yet there was no significant difference between QNZT-M and QNZT-H groups (P>0.05).Conclusion QNZT can reduce the NO level, increase the 5-HT level, alleviate the clinical symptoms of migraine rats, increase their pain threshold, and become dose-dependent within a certain dose range, which may be achieved by inhibiting the activation of NF-κB/iNOS/COX2 signaling pathway.
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