Banxia Xiexintang Regulates Autophagy of Interstitial Cells of Cajal in Gastric Antrum of Rats with Gastric Electric Dysrhythmia

ZHANG Di; LI Yujing; JI Jing; ZHANG Dongmei; CHEN Meng

doi:10.13422/j.cnki.syfjx.20230137

您当前的位置：

首页 >

文章列表页 >

Banxia Xiexintang Regulates Autophagy of Interstitial Cells of Cajal in Gastric Antrum of Rats with Gastric Electric Dysrhythmia

更新时间：2023-02-15

- Banxia Xiexintang Regulates Autophagy of Interstitial Cells of Cajal in Gastric Antrum of Rats with Gastric Electric Dysrhythmia
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 29, Issue 6, Pages: 55-62(2023)
- 作者机构：
  
  1.北京中医药大学中医学院，北京 100029
  2.北京中医药大学东直门医院，北京 100700
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20230137
  CLC： R2-0;R33;R289;R573
- Published：20 March 2023，
  
  Published Online：29 December 2022，
  
  Received：28 October 2022，
- 稿件说明：
扫描看全文
张迪,李雨静,吉静等.半夏泻心汤调节胃电节律失常大鼠胃窦Cajal间质细胞自噬的作用[J].中国实验方剂学杂志,2023,29(06):55-62.

ZHANG Di,LI Yujing,JI Jing,et al.Banxia Xiexintang Regulates Autophagy of Interstitial Cells of Cajal in Gastric Antrum of Rats with Gastric Electric Dysrhythmia[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(06):55-62.
张迪,李雨静,吉静等.半夏泻心汤调节胃电节律失常大鼠胃窦Cajal间质细胞自噬的作用[J].中国实验方剂学杂志,2023,29(06):55-62. DOI： 10.13422/j.cnki.syfjx.20230137.

ZHANG Di,LI Yujing,JI Jing,et al.Banxia Xiexintang Regulates Autophagy of Interstitial Cells of Cajal in Gastric Antrum of Rats with Gastric Electric Dysrhythmia[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(06):55-62. DOI： 10.13422/j.cnki.syfjx.20230137.

摘要

目的

通过观察半夏泻心汤对于胃电节律失常大鼠胃窦组织中Cajal间质细胞（ICCs）自噬的影响，探究其保护作用及调节机制。

方法

32只SD大鼠随机分为正常组、模型组、半夏泻心汤组（24.68 g·kg

-1

）及多潘立酮组（2.7 mg·kg

-1

）。通过“隔日进食+饮稀盐酸”法建立胃电节律失常大鼠模型，给予半夏泻心汤及阳性药多潘立酮进行干预。每周记录大鼠体质量；生物机能实验系统记录大鼠胃电活动；透射电子显微镜观察大鼠胃窦组织超微结构变化；免疫荧光双标法检测大鼠胃窦组织中酪氨酸激酶受体（c-kit）/自噬关键分子酵母Atg6同系物（Beclin1）共表达情况；蛋白免疫印迹法（Western blot）检测胃窦组织中微管相关蛋白1轻链3（LC3）B、p62蛋白表达，并计算LC3B Ⅱ/Ⅰ。

结果

与正常组比较，模型组大鼠体质量减轻（

0.01）；胃电主频率、主功率下降（

0.01）；电镜下观察到胃窦ICCs超微结构损伤，细胞器变性坏死，可见少量自噬泡；免疫荧光双标结果显示，胃窦组织中c-kit阳性表达减低，Beclin1阳性表达增加；Western blot结果显示，胃窦组织中LC3BⅡ/Ⅰ增加（

0.01），p62蛋白表达减低（

0.01）。与模型组比较，半夏泻心汤及多潘立酮能够增加大鼠体质量（

0.01），升高胃电主频率、主功率（

0.01），修复胃窦ICCs超微结构损伤，上调胃窦组织中c-kit阳性表达并下调Beclin1阳性表达，上调胃窦组织中p62表达（

0.05）；半夏泻心汤能够抑制胃窦组织中LC3B Ⅰ转化为LC3B Ⅱ（

0.05）。

结论

半夏泻心汤能够通过调节自噬相关蛋白的表达，降低ICCs细胞自噬，调节ICCs的数量及结构，从而改善大鼠胃电节律失常，阐释了半夏泻心汤治疗“心下痞”的作用内涵。

Abstract

Objective

To observe the effect of Banxia Xiexintang on the autophagy of interstitial cells of Cajal （ICCs） in the gastric antrum of rats with gastric electric dysrhythmia， and explore the protective effect and regulatory mechanism.

Method

Thirty-two SD rats were randomly assigned into a normal group， a model group， a Banxia Xiexintang （24.68 g·kg

-1

） group， and a positive drug （2.7 mg·kg

-1

） group. The rat model of gastric electric dysrhythmia was established by the method of dieting every other day and drinking dilute hydrochloric acid， and Banxia Xiexintang and the positive drug were administrated for intervention. The body weight of each rat was recorded weekly. The gastric electric activity was recorded by the biological function experimental system. The ultrastructural changes of the gastric antrum tissue were observed by a transmission electron microscope. The co-expression of receptor tyrosine kinase （c-kit）/mammalian homolog of yeast Atg6 （Beclin1） in the gastric antrum tissue was detected by double immunofluorescence labeling method. The expression of microtubule-associated protein 1 light chain 3B （LC3B） and p62 protein in the gastric antrum tissue was determined by Western blot， and the LC3BⅡ/Ⅰ ratio was calculated.

Result

Compared with the normal group， the modeling reduced the body weight （

0.01） and decreased the dominant frequency and dominant power of gastric electricity （

0.01）. In addition， the modeling caused ultrastructural damage of ICCs in gastric antrum， degeneration and necrosis of organelles， and appearance of a small number of autophagic vesicles. The results of double immunofluorescence labeling showed that the modeling inhibited the positive expression of c-kit and promoted the positive expression of Beclin1 in gastric antrum tissue. Western blot results showed that the modeling increased the ratio of LC3BⅡ/Ⅰ （

0.01） and down-regulated the expression of p62 protein （

0.01） in the gastric antrum tissue. Compared with the model group， Banxia Xiexintang and the positive drug increased the body weight （

0.01） and the dominant frequency and dominant power of gastric electricity （

0.01）， repaired the ultrastructural damage of ICCs in gastric antrum tissue， promoted the positive expression of c-kit and inhibited the positive expression of Beclin1 in the gastric antrum tissue. Furthermore， Banxia Xiexintang up-regulated the expression of p62 （

0.05） and inhibited the transformation of LC3BⅠ into LC3BⅡ in gastric antrum tissue （

0.05）.

Conclusion

By regulating the expression of autophagy-related proteins， Banxia Xiexintang can reduce the autophagy and regulate the number and structure of ICCs and thus improve the gastric electric rhythm of rats， which preliminarily explains the mechanism of Banxia Xiexintang in the treatment of epigastric stuffiness.

关键词

半夏泻心汤Cajal间质细胞自噬胃电节律失常心下痞

Keywords

Banxia Xiexintanginterstitial cells of Cajalautophagygastric electric dysrhythmiaepigastric stuffiness

references

DEANE A M，CHAPMAN M J，REINTAM B A，et al.Pathophysiology and treatment of gastrointestinal motility disorders in the acutely ill［J］.Nutr Clin Pract，2019，34（1）：23-36.

MILLER J，KHLEVNER J，RODRIGUEZ L.Upper gastrointestinal functional and motility disorders in children［J］.Pediatr Clin North Am，2021，68（6）：1237-1253.

于红珍，付明海，吉小平，等.简述胃肠动力调节机制的研究进展［J］.世界华人消化杂志，2020，28（23）：1183-1191.

WARD S M，SANDERS K M，HIRST G D．Role of interstitial cells of Cajal in neural control of gastrointestinal smooth muscles［J］.Neurogastroenterol Motil，2004，16（Suppl1）：112-117.

KLEIN S，SEIDLER B，KETTENBERGER A，et al.Interstitial cells of Cajal integrate excitatory and inhibitory neurotransmission with intestinal slow-wave activity［J］.Nat Commun，2013，4（5）：1630.

FOONG D，ZHOU J，ZARROUK A，et al.Understanding the biology of human interstitial cells of Cajal in gastrointestinal motility［J］.Int J Mol Sci，2020，21（12）：4540.

常宗宏，邓尚新，杨娟，等.Cajal间质细胞在胃肠动力障碍性疾病中的研究［J］.胃肠病学和肝病学杂志，2019，28（4）：387-390.

ANGELI T R，CHENG L K，DU P，et al.Loss of interstitial cells of Cajal and patterns of gastric dysrhythmia in patients with chronic unexplained nausea and vomiting［J］.Gastroenterology，2015，149（1）：56-66.

王飞，陆瑞敏，王淑艳，等.半夏泻心汤对小鼠Cajal间质细胞表型维持及相关钙离子通道蛋白的影响［J］.环球中医药，2021，14（1）：8-13.

赵冉冉，王梦薇，王启航，等.半夏泻心汤含药血清对大鼠胃Cajal间质细胞凋亡相关蛋白表达及eNOS、NO分泌的影响［J］.中医杂志，2021，62（10）：893-897.

陈萌.半夏泻心汤调节胃电节律的拆方研究［D］.北京：北京中医药大学，2003.

张勇，王振华.大鼠胃电节律失常模型的建立［J］.华人消化杂志，1998，doi：10.3969/j.issn.1009-3079.1998.07.021http://dx.doi.org/10.3969/j.issn.1009-3079.1998.07.021.

李亚欢.半夏泻心汤对胃电节律失常模型大鼠胃组织microRNA的影响［D］.北京：北京中医药大学，2018.

柯雪帆.现代中医药应用与研究大系·第四卷·伤寒及金匮［M］.上海：上海中医药大学出版社，1995：140-144.

MIWA H，WATARI J，FUKUI H，et al.Current understanding of pathogenesis of functional dyspepsia［J］.J Gastroenterol Hepatol，2011，26（Suppl 3）：53-60.

SHAFIK A，AHMED I，SIBAI O E，et al.Interstitial cells of cajal in reflux esophagitis：Role in the pathogenesis of the disease［J］.Med Sci Monit，2005，11（12）：452.

邢枫，陶艳艳，李爽，等.基于胃肠动力调节与透皮吸收探讨中药外用制剂消胀贴膏治疗肝硬化腹水的作用机制［J］.世界中医药，2016，11（7）：1357-1361.

SINGH R，HA S E，WEI L，et al.miR-10b-5p rescues diabetes and gastrointestinal dysmotility［J］.Gastroenterology，2021，160（5）：1662-1678.

KROEMER B L.Autophagy in aging，disease，and death：The true identity of a cell death impostor ［J］.Cell Death Differ，2009，16（1）：1-2.

WEI X，LIN Y，ZHAO D，et al.Electroacupuncture relieves suppression of autophagy in interstitial cells of Cajal of diabetic gastroparesis rats［J］.Can J Gastroenterol Hepatol，2020，doi：10.1155/2020/7920715http://dx.doi.org/10.1155/2020/7920715.

潘小丽，周丽，王丹，等.电针“足三里”对功能性消化不良大鼠胃排空及自噬信号通路的影响［J］.针刺研究，2019，44（7）：486-491.

RUBINSZTEIN D C，CODOGNO P，LEVINE B.Autophagy modulationas a potential therapeutic target for diverse diseases［J］.Nat Rev Drug Discov，2012，11（9）：709-730．

KLIONSKY D J，PETRONI G，AMARAVADI R K，et al.Autophagy in major human diseases［J］.EMBO J，2021，40（19）：e108863.

XU H D，QIN Z H.Beclin 1，Bcl-2 and autophagy［J］.Adv Exp Med Biol，2019，1206：109-126.

WEI F，JIANG X，GAO H Y，et al.Liquiritin induces apoptosis and autophagy in cisplatin （DDP）-resistant gastric cancer cells in vitro and xenograft nude mice in vivo［J］.Int J Oncol，2017，51（5）：1383-1394.

DIKIC I，ELAZAR Z.Mechanism and medical implications of mammalian autophagy［J］.Nat Rev Mol Cell Biol，2018，19（6）：349-364.

陆瑞敏.基于miRNA-451-5p靶向SCF/c-kit探讨半夏泻心汤干预ICC凋亡的研究［D］.北京：北京中医药大学，2021.

WANG G，ZHANG T，SUN W，et al.Arsenic sulfide induces apoptosis and autophagy through the activation of ROS/JNK and suppression of Akt/mTOR signaling pathways in osteosarcoma［J］.Free Radic Biol Med，2017，106：24-37.

MAIURI M C，ZALCKVAR E，KIMCHI A，et al.Self-eating and self-killing：Crosstalk between autophagy and apoptosis［J］.Nat Rev Mol Cell Biol，2007，8（9）：741-752.

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Curative Effect and Mechanism of Traditional Chinese Medicine in Treatment of Diabetic Gastroenteropathy： A Review

Effect of Huangjingwan on Hippocampal Autophagy in Mouse Model of Learning and Memory Impairments

Role of Autophagy in Ovarian Cancer Based on Yin and Yang Theory

Icariin Regulates Glucocorticoid-induced Autophagy of Bone Microvascular Endothelial Cells Through PI3K/Akt/mTOR Pathway

Related Author

YIN Ruiyang

ZHANG Yuxin

ZHANG Yanjiao

FANG Xinyi

MIAO Runyu

GUAN Huifang

TIAN Jiaxing

LIAO Kexin

Related Institution

Institute of Metabolic Diseases， Guang'anmen Hospital， China Academy of Chinese Medical Sciences

Graduate School， Beijing University of Chinese Medicine

Graduate School， Changchun University of Chinese Medicine

College of Chinese Medicine， Jiangxi University of Chinese Medicine

Heilongjiang University of Chinese Medicine

Postal code：100700
Tel：010-84076882 Email：syfjx_2010@188.com
Technical support is provided by Beijing Founder electronics co., LTD 京ICP备11006657号-10 京公网安备11010802024621
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.

⁰