Mechanism of Qi-invigorating and Blood-activating Therapy in Mediating Autophagy of Precancerous Lesions of Atrophic Gastritis by miR216b/Beclin1

ZHAO Weihan; ZHOU Ying; XU Yuqing; AI Yanan; WEN Wen; MU Heng

doi:10.13422/j.cnki.syfjx.20230990

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Mechanism of Qi-invigorating and Blood-activating Therapy in Mediating Autophagy of Precancerous Lesions of Atrophic Gastritis by miR216b/Beclin1

更新时间：2023-04-13

- Mechanism of Qi-invigorating and Blood-activating Therapy in Mediating Autophagy of Precancerous Lesions of Atrophic Gastritis by miR216b/Beclin1
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 29, Issue 10, Pages: 117-122(2023)
- 作者机构：
  
  1.陕西中医药大学附属医院，陕西咸阳 712000
  2.陕西中医药大学，陕西咸阳 712046
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20230990
  CLC： R242;R2-0;R2-031;R24;R285;R573.3
- Received：26 December 2021，
  
  Published Online：17 May 2022，
  
  Published：20 May 2023
- 稿件说明：
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赵唯含,周莹,许雨晴等.益气活血法通过miR216b/Beclin1介导萎缩性胃炎癌前病变自噬的机制[J].中国实验方剂学杂志,2023,29(10):117-122.

ZHAO Weihan,ZHOU Ying,XU Yuqing,et al.Mechanism of Qi-invigorating and Blood-activating Therapy in Mediating Autophagy of Precancerous Lesions of Atrophic Gastritis by miR216b/Beclin1[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(10):117-122.
赵唯含,周莹,许雨晴等.益气活血法通过miR216b/Beclin1介导萎缩性胃炎癌前病变自噬的机制[J].中国实验方剂学杂志,2023,29(10):117-122. DOI： 10.13422/j.cnki.syfjx.20230990.

ZHAO Weihan,ZHOU Ying,XU Yuqing,et al.Mechanism of Qi-invigorating and Blood-activating Therapy in Mediating Autophagy of Precancerous Lesions of Atrophic Gastritis by miR216b/Beclin1[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(10):117-122. DOI： 10.13422/j.cnki.syfjx.20230990.

摘要

目的

通过观察益气活血法对萎缩性胃炎癌前病变（PLGC）模型小鼠微RNA216b（miR216b）/自噬关键分子酵母Atg6同系物1（Beclin1）信号通路的影响，探讨其干预PLGC的自噬作用机制。

方法

将75只健康雄性SPF级昆明种小鼠随机分为空白组（12只）及造模组（63只），造模组小鼠每日采用1-甲基-3-硝基-1-亚硝基胍（MNNG）溶液（150 mg·L

-1

）自由饮用及灌胃，同时每日灌胃雷尼替丁溶液（0.03 g·kg

-1

），造模12周。按照随机对照表将造模小鼠分为模型组、益气组（黄芪3.5 g·kg

-1

）、活血组（三七粉0.7 g·kg

-1

）、益气活血组（黄芪3.5 g·kg

-1

+三七粉0.7 g·kg

-1

）及叶酸组（2 mg·kg

-1

）。予相应药物灌胃8周后取材，苏木素-伊红（HE）染色观察小鼠胃黏膜病理改变，蛋白免疫印迹法（Western blot）检测胃组织微管相关蛋白1轻链3（LC3）Ⅰ、LC3Ⅱ、Beclin1蛋白表达，实时荧光定量聚合酶链式反应（Real-time PCR）检测各组胃黏膜Beclin1及miR-216b的mRNA表达情况。

结果

与空白组比较，病理学观察显示模型组胃黏膜固有腺体减少，出现萎缩伴肠上皮化生；与模型组比较，各治疗组均有改善，其中益气活血组改善最为明显。与空白组比较，模型组小鼠胃组织LC3Ⅰ、LC3Ⅱ、LC3Ⅱ/LC3Ⅰ及Beclin1蛋白含量均明显降低（

0.05）。与模型组比较，各治疗组胃组织LC3Ⅰ、LC3Ⅱ、LC3Ⅱ/LC3Ⅰ及Beclin1蛋白含量均有升高（

0.05，

0.01），其中益气活血组升高最为明显。与空白组比较，模型组小鼠Beclin1 mNRA表达下降（

0.05），miR216b mNRA表达上升（

0.05）。与模型组比较，各治疗组小鼠Beclin1表达升高（

0.05），miR216b表达下降（

0.05），尤以益气活血组最为明显。

结论

以黄芪、三七为代表的益气活血法治疗PLGC的作用机制可能为通过抑制miR216b的表达，激活Beclin1，从而促进自噬，发挥修复胃黏膜的作用。

Abstract

Objective

To investigate the effect of Qi-invigorating and blood-activating therapy on the miR216b/Beclin1 pathway in mice with atrophic precancerous lesions of gastric cancer （PLGC） and analyze its mechanism in autophagy of PLGC.

Method

Seventy-five healthy male SPF KM mice were randomly divided into a blank group and a model group. Mice in the model group were given 1-methyl-3-nitroso-1-nitrosoguanidine （MNNG） solution （150 mg·L

-1

） for free drinking and gavage and ranitidine solution （0.03 g·kg

-1

） daily for 12 weeks. According to the random control table， mice were divided into a model group， a Qi-invigorating group （3.5 g·kg

-1

of Astragali Radix）， a blood-activating group （0.7 g·kg

-1

of Notoginseng Radix et Rhizoma powder）， a Qi-invigorating and blood-activating group （3.5 g·kg

-1

of Astragali Radix + 0.7 g·kg

-1

of Notoginseng Radix et Rhizoma powder）， and a folic acid group （2 mg·kg

-1

）. The corresponding drugs were given to mice in each group for 8 weeks and then the tissues were collected. Hematoxylin-eosin （HE） staining was carried out to observe the changes in gastric mucosa. Western blot was used to detect the protein expression of microtuble-associated protein 1 light chain 3 （LC3）Ⅰ， LC3Ⅱ， and Beclin1. Real-time polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of Beclin1 and miR-216b.

Result

Pathological observation showed that as compared with the blank group， the intrinsic glands of gastric mucosa decreased with atrophy and intestinal metaplasia in the model group， which were improved in all treatment groups， and the improvement of the Qi-invigorating and blood-activating group was the most obvious. As compared with the blank group， the content of LC3Ⅰ， LC3Ⅱ， LC3Ⅱ/LC3Ⅰ， and Beclin1 protein in gastric tissues of the model group was significantly decreased （

0.05）. As compared with the model group， the content of LC3Ⅰ， LC3Ⅱ， LC3Ⅱ/LC3Ⅰ， and Beclin1 protein in gastric tissues of each treatment group was increased （

0.05，

0.01）. The increase was most obvious in the Qi-invigorating and blood-activating group. As compared with the blank group， the mRNA expression of Beclin1 in the model group was decreased （

0.05）， and that of miR216b was increased （

0.05）. As compared with the model group， the mRNA expression of Beclin1 was increased and that of miR216b was decreased in each treatment group （

0.05）， and the changes were the most obvious in the Qi-invigorating and blood-activating group.

Conclusion

The mechanism of the Qi-invigorating and blood-activating therapy， represented by Astragali Radix and Notoginseng Radix et Rhizoma， in treating PLGC may be through inhibiting the expression of miR216b and activating Beclin1， thus promoting autophagy and repairing gastric mucosa.

关键词

Keywords

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