Effect of <italic style="font-style: italic">Qingyu Hejiang Decoction</italic>（清郁和降汤）on LPS/TLR4/NFκB Pathway and Esophageal Mucosal Barrier in Reflux Esophagitis Model Rats

HUANG Yuqing; ZHOU Yi; HUANG He; YE Song

doi:10.13288/j.11-2166/r.2022.22.014

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Effect of Qingyu Hejiang Decoction（清郁和降汤）on LPS/TLR4/NFκB Pathway and Esophageal Mucosal Barrier in Reflux Esophagitis Model Rats

更新时间：2022-11-11

- Effect of Qingyu Hejiang Decoction（清郁和降汤）on LPS/TLR4/NFκB Pathway and Esophageal Mucosal Barrier in Reflux Esophagitis Model Rats
- Journal of Traditional Chinese Medicine Vol. 63, Issue 22, Pages: 2170-2178(2022)
- 作者机构：
  
  1.湖北中医药大学，湖北省武汉市洪山区黄家湖西路16号，430065
  2.湖北省中医院
- 作者简介：
- 基金信息：
- DOI：10.13288/j.11-2166/r.2022.22.014
  CLC：
- Received：01 March 2022，
  
  Revised：2022-06-30，
  
  Published：17 November 2022
- 稿件说明：
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黄雨晴,周易,黄鹤等.清郁和降汤对反流性食管炎模型大鼠食管组织LPS/TLR4/NF-κB通路及食管黏膜屏障的影响[J].中医杂志,2022,63(22):2170-2178.

HUANG Yuqing,ZHOU Yi,HUANG He,et al.Effect of Qingyu Hejiang Decoction（清郁和降汤）on LPS/TLR4/NFκB Pathway and Esophageal Mucosal Barrier in Reflux Esophagitis Model Rats[J].Journal of Traditional Chinese Medicine,2022,63(22):2170-2178.
黄雨晴,周易,黄鹤等.清郁和降汤对反流性食管炎模型大鼠食管组织LPS/TLR4/NF-κB通路及食管黏膜屏障的影响[J].中医杂志,2022,63(22):2170-2178. DOI： 10.13288/j.11-2166/r.2022.22.014.

HUANG Yuqing,ZHOU Yi,HUANG He,et al.Effect of Qingyu Hejiang Decoction（清郁和降汤）on LPS/TLR4/NFκB Pathway and Esophageal Mucosal Barrier in Reflux Esophagitis Model Rats[J].Journal of Traditional Chinese Medicine,2022,63(22):2170-2178. DOI： 10.13288/j.11-2166/r.2022.22.014.

摘要

目的

探讨清郁和降汤治疗反流性食管炎（RE）的可能作用机制。

方法

60只雄性SD大鼠中随机选择10只为假手术组，另外50只采用“前胃结扎+外置幽门部分结扎术”建立反流性食管炎模型。将造模成功的40只大鼠随机分成模型组、清郁和降汤组、雷贝拉唑+莫沙比利组和中西药联用组，每组10只。造模后假手术组及模型组分别予蒸馏水1 ml/100 g灌胃，清郁和降汤组予浓度为1.58 g/ml的清郁和降汤灌胃，雷贝拉唑+莫沙比利组予浓度为0.21 mg/ml的雷贝拉唑钠肠溶胶囊溶液和浓度为0.16 mg/ml的枸橼酸莫沙比利分散片溶液灌胃，中西药联用组予清郁和降汤、雷贝拉唑钠肠溶胶囊、枸橼酸莫沙比利分散片灌胃，剂量同上。各组灌胃量均为1 ml/100 g，持续14天。观察大鼠食管组织的病理学改变；检测大鼠血清中及食管组织中脂多糖（LPS）、白细胞介素1β（IL-1β）、白细胞介素6（IL-6）、白细胞介素8（IL-8）含量；检测食管组织中Toll样受体4（TLR4）、核转录因子κB（NF-κB） p65、封闭蛋白1（Cldn1）、封闭蛋白4（Cldn4） mRNA及蛋白表达水平。

结果

与假手术组比较，模型组大鼠食管黏膜损伤严重，肉眼观察可见充血、糜烂或溃疡，镜下可见食管鳞状上皮增厚并伴有基底细胞增生，黏膜固有层乳头延伸，大量炎性细胞浸润；与模型组比较，各给药组食管黏膜损伤明显减轻。与假手术组比较，模型组大鼠血清及食管组织LPS、IL-1β、IL-6、IL-8表达升高（

＜0.01），食管组织TLR4、NF-κB p65 mRNA和蛋白表达升高，Cldn1、Cldn4 mRNA和蛋白表达降低（

＜0.01）；与模型组比较，各给药组大鼠血清及食管组织LPS、IL-1β、IL-6、IL-8表达降低（

＜0.01），食管组织TLR4、NF-κB p65 mRNA及蛋白表达降低，Cldn1、Cldn4 mRNA及蛋白表达升高（

＜0.05或

＜0.01）。与中西药联用组比较，清郁和降汤组、雷贝拉唑+莫沙比利组大鼠血清及食管组织LPS、IL-1β、IL-6、IL-8表达明显升高，TLR4、NF-κB p65蛋白表达明显升高，Cldn1、Cldn4 mRNA及蛋白表达明显降低（

＜0.05或

＜0.01）；与雷贝拉唑+莫沙比利组比较，清郁和降汤组大鼠血清LPS表达明显降低，食管组织IL-8表达及TLR4蛋白表达明显升高，Cldn4 蛋白表达明显降低（

＜0.05或

＜0.01）。

结论

清郁和降汤能够减轻RE大鼠食管黏膜损伤，与雷贝拉唑+莫沙比利联用具有协同作用，其机制可能与抑制食管组织LPS/TLR4/NF-κB通路，减轻食管炎症，增强食管上皮屏障功能有关。

Abstract

Objective

To explore the potential mechanism of

Qingyu Hejiang Decoction

（清郁和降汤， QHD） in the treatment of reflux esophagitis （RE）.

Methods

Ten out of 60 male SD rats were randomly selected as sham operation group， and the other 50 rats were treated with anterior gastric ligation and external pyloric partial ligation to establish the RE model. Forty successful models were randomly divided into model group， QHD group， rabeprazole + mosapride group and integrated traditional Chinese and western medicine group （integrated group）， with 10 rats in each group. After modeling， the rats in the sham operation group and the model group were perfused with 1 ml/100 g of distilled water， while those in the QHD group were given 1.58 g/ml of QHD， and those in the rabeprazole + mosapride group were treated with 0.21 mg/ml of rabeprazole sodium enteric-coated capsule plus 0.16 mg/L of mosapride citrate dispersible tablet； rats in the integrated medicine group were treated with QHD， rabeprazole， and mosapride， in the same administration way as mentioned above. All the interventions were given at the dose of 1 ml/100 g by gavage， for 14 days. The pathological changes of rat esophagus were observed， and the contents of lipopolysaccharide （LPS）， interleukin-1β （IL-1β）， interleukin-6 （IL-6） and interleukin-8 （IL-8） in serum and esophageal tissue were detected. The mRNA levels and protein expressions of Toll-like receptor 4 （TLR4）， nuclear transcription factor κB （NF-κB） p65， occludin 1 （Cldn1） and occludin 4 （Cldn4） in esophageal tissue were detected.

Results

compared to those in the sham operation group， the esophageal mucosa of the model group was seriously injured， and hyperemia， erosion or ulcer could be seen with naked eyes， as well as thickening of esophageal squamous epithelium， proliferation of basal cells， extension of lamina propria papilla and infiltration of a large number of inflammatory cells seen under microscope. Compared to that in the model group， esophageal mucosal injury in other three intervention groups was significantly alleviated. Compared to those in the sham operation group， the expression of LPS， IL-1β， IL-6 and IL-8 in serum and esophageal tissue significantly increased in the model group （

＜0.01）， while the mRNA and protein expressions of TLR4 and NF-κB p65 increased， and the expressions of Cldn1， Cldn4 significantly decreased in the esophageal tissue （

＜0.01）. Compared to those in the model group， the expressions of LPS， IL-1β， IL-6 and IL-8 in serum and esophageal tissue in other three intervention groups significantly decreased （

＜0.01）， and the mRNA and protein expressions of TLR4 and NF- κ B p65 in esophageal tissue also significantly decreased， but the expressions of Cldn1 and Cldn4 significantly increased （

＜0.01 or

＜0.05）. Compared to those in the integrated medicine group， the expressions of LPS， IL-1β， IL-6 and IL-8 in serum and esophagus tissue in the QHD group and the rabeprazole + mosapride group significantly increased， as well as the protein expression of TLR4 and NF-κB p65， while mRNA and protein expression of Cldn1 and Cldn4 significantly decreased （

＜0.05 or

＜0.01）. The expression of LPS in serum significantly decreased in the QHD group compared to the rabeprazole + mosapride group， while the expression of IL-8 and TLR4 protein in esophageal tissue significantly increased， and the expression of Cldn4 protein was significantly reduced （

＜0.05 or

＜0.01）.

Conclusion

QHD can alleviate the injury of esophageal mucosa in RE rats， and has a synergistic effect when used together with rabeprazole + mosapride. The underlying mechanism may be related to the inhibition of LPS/TLR4/NF-κB pathway， reduction of esophageal inflammation and enhancement of esophageal epithelial barrier function.

关键词

Keywords

references

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Effect of Qingyu Hejiang Decoction（清郁和降汤）on LPS/TLR4/NFκB Pathway and Esophageal Mucosal Barrier in Reflux Esophagitis Model Rats

DOI：10.13288/j.11-2166/r.2022.22.014

摘要

Abstract

关键词

Keywords

references