成映霞 周语平 段永强 王强 杨亚楠 李兰珍 杨晓轶 段云燕 杜娟 王庆胜

摘要：目的 观察香砂六君子汤对脾胃虚弱型慢性萎缩性胃炎（CAG）大鼠胃黏膜组织病理改变、核因子-κB （NF-κB）p65活化水平及其介导的炎性因子肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-1β、IL-8和IL-12表达的影响，探讨其作用机制。方法 实验大鼠按随机数字表法分为空白组和造模组，采用综合法制作脾胃虚弱型CAG大鼠模型，将成模大鼠随机分为模型组、阳性对照组和香砂六君子汤高、中、低剂量组。空白组和模型组予10 mL/（kg·d）蒸馏水灌胃，香砂六君子汤高、中、低剂量组分别予24、12、6 g/（kg·d）香砂六君子汤药液灌胃，阳性对照组予0.3 g/（kg·d）维酶素药液灌胃，给药120 d后检测大鼠胃黏膜TNF-α、IL-1β、IL-8和IL-12含量，实时荧光定量PCR检测大鼠胃黏膜组织NF-κB p65及下游炎性因子TNF-α、IL-1β、IL-8、IL-12基因表达，Western blot检测NF-κB p65蛋白表达。结果 与空白组比较，模型组大鼠一般生存状况较差，病理显示胃黏膜明显变薄，腺体萎缩、排列稀疏而紊乱；胃黏膜组织NF-κB p65 mRNA和蛋白表达显著升高（P<0.01），促炎因子TNF-α、IL-1β、IL-8和IL-12含量及mRNA表达显著升高（P<0.05，P<0.01）；与模型组比较，香砂六君子汤高剂量组大鼠一般生存状况显著改善，胃黏膜萎缩变薄等病理显著改善，胃黏膜组织NF-κB p65 mRNA和蛋白表达显著降低（P<0.05，P<0.01），TNF-α、IL-1β、IL-8和IL-12含量及mRNA表达显著降低（P<0.05）。结论 香砂六君子汤可能通过下调NF-κB p65基因和蛋白表達，抑制促炎因子TNF-α、IL-1β、IL-8和IL-12异常分泌而发挥保护胃黏膜的作用。

关键词：香砂六君子汤；慢性萎缩性胃炎；核因子-κB p65；肿瘤坏死因子-α；白细胞介素-1β；白细胞介素-8；白细胞介素-12；大鼠

DOI：10.3969/j.issn.1005-5304.2018.05.012

中图分类号：R285.5 文献标识码：A 文章编号：1005-5304（2018）05-0050-06

Effects of Xiangsha Liujunzi Decoction on Activated Levels of NF-κB p65

and Inflammatory Cascade Reaction Mediated by NF-κB p65 of

Gastric Mucosa in Chronic Atrophic Gastritis Rats

CHENG Ying-xia1，2，3， ZHOU Yu-ping2， DUAN Yong-qiang2，3， WANG Qiang2，3， YANG Ya-nan4， LI Lan-zhen2，

YANG Xiao-yi1， DUAN Yun-yan2， DU Juan2， WANG Qing-sheng1

1. Key Laboratory of Pharmacology and Toxicology for TCM of Gansu Province， Lanzhou 730000， China；2. Gansu University of Chinese Medicine， Lanzhou 730000， China； 3. Key Laboratory of Traditional Chinese Herbs and Prescription Innovation and Transformation of Gansu Province， Lanzhou 730000， China； 4. Xian Jiaotong

University Health Science Center， Xi'an 710061， China

Abstract： Objective To observe the effects of Xiangsha Liujunzi Decoction on histopathological changes of gastric antrum， activated levels of NF-κB p65 in gastric mucosa and expression levels of inflammatory factors including TNF-α， IL-1β， IL-8 and IL-12 mediated by NF-κB p65 of chronic atrophic gastritis （CAG） rats with spleen-stomach deficiency syndrome； To discuss its mechanism of action. Methods The experimental rats were

基金项目：国家自然科学基金（81260519、81760830）；甘肃省自然科学基金（1610RJZA063）；甘肃省中医药管理局资助项目（GZK-2014-73）；甘肃省中医方药挖掘与创新转化重点实验室开放基金（ZYFYZH-KJ-2016-006）

divided into blank group and model group according to the random number table method. The model of CAG rats with spleen-stomach deficiency syndrome was successfully duplicated by comprehensive method. And then the rats were randomly divided into model group， Xiangsha Liujunzi Decoction high-， medium- and low-dose groups and positive control group. The rats in blank and model groups were given 10 mL/（kg·d） distilled water， and Xiangsha Liujunzi Decoction high-， medium- and low-dose groups were given 24， 12， 6 g/（kg·d） Xiangsha Liujunzi Decoction respectively， the positive control group was treated with 0.30 g/（kg·d） vitamin enzyme. 120 days later， the levels of TNF-α， IL-1β， IL-8 and IL-12 in gastric mucosa were detected. Gene expression of NF-κB p65 in gastric mucosa and the above inflammatory factors were detected with real-time fluorescence quantitative PCR， and protein expression of NF-κB p65 was detected by Western blot. Results Compared with the blank group， the general living condition of the model rats was poor， and the pathological changes showed that the gastric mucosa became thinner， the glands were atrophic and its arrangement was sparse and disorder. The expression of NF-κB p65 mRNA and protein in gastric tissue significantly increased （P<0.01）， and the levels of TNF-α， IL-1β， IL-8 and IL-12 significantly increased （P<0.05， P<0.01）. Compared with model group， the normal survival status of the rats in Xiangsha Liujunzi Decoction high- and medium-dose groups was significantly improved， and the pathological changes of the gastric mucosal atrophy and other pathological changes were significantly improved. Gene and protein expression of NF-κB p65 in gastric tissues decreased significantly （P<0.05， P<0.01）， and mRNA and the contents of TNF-α， IL-1β， IL-8 and IL-12 decreased significantly （P<0.05）. Conclusion Xiangsha Liujunzi Decoction plays an important role in protecting the gastric mucosa by down-regulating the expression of NF-κB p65 gene and protein and inhibiting the abnormal secretion of proinflammatory cytokines TNF-α， IL-1β， IL-8 and IL-12.

Keywords： Xiangsha Liujunzi Decoction； chronic atrophic gastritis； NF-κB p65； TNF-α； IL-1β； IL-8； IL-12； rats

慢性萎縮性胃炎（chronic atrophic gastritis，CAG）病理机制之一在于胃黏膜慢性炎性级联反应放大和细胞增殖与凋亡失衡而造成胃黏膜持续损伤[1]。临床应用香砂六君子汤及其加减方治疗CAG疗效显著[2]。……