Electroacupuncture Alleviates Functional Constipation in Mice by Activating Enteric Glial Cell Autophagy via PI3K/AKT/mTOR Signaling
Objective To investigate autophagy-related mechanisms of electroacupuncture (EA) action in improving gastrointestinal motility in mice with functional constipation (FC). Methods According to a random number table, the Kunming mice were divided into the normal control, FC and EA groups in Experiment...
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| Veröffentlicht in: | Chinese journal of integrative medicine 2023-05, Vol.29 (5), p.459-469 |
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| creator | Wang, Lu Chen, Ying Xu, Ming-min Cao, Wei Zheng, Qian-hua Zhou, Si-yuan Yao, Jun-peng Xi, Meng-han Qin, Hai-yan Li, Ying Zhang, Wei |
| description | Objective
To investigate autophagy-related mechanisms of electroacupuncture (EA) action in improving gastrointestinal motility in mice with functional constipation (FC).
Methods
According to a random number table, the Kunming mice were divided into the normal control, FC and EA groups in Experiment I. The autophagy inhibitor 3-methyladenine (3-MA) was used to observe whether it antagonized the effects of EA in Experiment II. An FC model was established by diphenoxylate gavage. Then the mice were treated with EA stimulation at Tianshu (ST 25) and Shangjuxu (ST 37) acupoints. The first black stool defecation time, the number, weight, and water content of 8-h feces, and intestinal transit rate were used to assess intestinal transit. Colonic tissues underwent histopathological assessment, and the expressions of autophagy markers microtubule-associated protein 1 light chain 3 (LC3) and Beclin-1 were detected by immunohistochemical staining. The expressions of phosphoinositide 3-kinases (PI3K)-protein kinase B (AKT)-mammalian target of rapamycin (mTOR) signaling pathway members were investigated by Western blot and quantitative reverse transcription-polymerase chain reaction, respectively. The relationship between enteric glial cells (EGCs) and autophagy was observed by confocal immunofluorescence microscopy, localization analysis, and electron microscopy.
Results
EA treatment shortened the first black stool defecation time, increased the number, weight, and water content of 8-h feces, and improved the intestinal transit rate in FC mice (
P |
| doi_str_mv | 10.1007/s11655-023-3594-3 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2807924089</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2807924089</sourcerecordid><originalsourceid>FETCH-LOGICAL-c344t-50f7462a94031d9db0825085eaf9b82567df76bccf51ac63efe615af3af4d163</originalsourceid><addsrcrecordid>eNp9kDtPwzAUhS0EgvL4ASzII0uoH7FTj1HVlooiEHS3HMcuRmkS7KRSd344jloYme651-ccWR8Atxg9YISyccCYM5YgQhPKRJrQEzDCQtAEpYicRs0zEjVmF-AyhE-EWMYROwcXlIuMMiJG4HtWGd35Rum-7Wvd9d7AvKrMzqnOBDgfbq6pVQWnTR0616phha6Gz04bWOxhHg27eK03cFZ3xjsNF5UbAqaqYN53TfuhNnsYG-Hrkj6N86f1eLt-eYPvbhOLY_AanFlVBXNznFdgPZ-tp4_J6mWxnOarRNM07RKGbJZyokSKKC5FWaAJYWjCjLKiiJJnpc14obVlWGlOjTUcM2WpsmmJOb0C94fa1jdfvQmd3Lqg4y9VbZo-SDJBmSApmohoxQer9k0I3ljZerdVfi8xkgN7eWAvI3s5sJc0Zu6O9X2xNeVf4hd2NJCDIcSnemO8_Gx6HxGEf1p_AM1mkEE</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2807924089</pqid></control><display><type>article</type><title>Electroacupuncture Alleviates Functional Constipation in Mice by Activating Enteric Glial Cell Autophagy via PI3K/AKT/mTOR Signaling</title><source>MEDLINE</source><source>Alma/SFX Local Collection</source><source>SpringerLink Journals - AutoHoldings</source><creator>Wang, Lu ; Chen, Ying ; Xu, Ming-min ; Cao, Wei ; Zheng, Qian-hua ; Zhou, Si-yuan ; Yao, Jun-peng ; Xi, Meng-han ; Qin, Hai-yan ; Li, Ying ; Zhang, Wei</creator><creatorcontrib>Wang, Lu ; Chen, Ying ; Xu, Ming-min ; Cao, Wei ; Zheng, Qian-hua ; Zhou, Si-yuan ; Yao, Jun-peng ; Xi, Meng-han ; Qin, Hai-yan ; Li, Ying ; Zhang, Wei</creatorcontrib><description>Objective
To investigate autophagy-related mechanisms of electroacupuncture (EA) action in improving gastrointestinal motility in mice with functional constipation (FC).
Methods
According to a random number table, the Kunming mice were divided into the normal control, FC and EA groups in Experiment I. The autophagy inhibitor 3-methyladenine (3-MA) was used to observe whether it antagonized the effects of EA in Experiment II. An FC model was established by diphenoxylate gavage. Then the mice were treated with EA stimulation at Tianshu (ST 25) and Shangjuxu (ST 37) acupoints. The first black stool defecation time, the number, weight, and water content of 8-h feces, and intestinal transit rate were used to assess intestinal transit. Colonic tissues underwent histopathological assessment, and the expressions of autophagy markers microtubule-associated protein 1 light chain 3 (LC3) and Beclin-1 were detected by immunohistochemical staining. The expressions of phosphoinositide 3-kinases (PI3K)-protein kinase B (AKT)-mammalian target of rapamycin (mTOR) signaling pathway members were investigated by Western blot and quantitative reverse transcription-polymerase chain reaction, respectively. The relationship between enteric glial cells (EGCs) and autophagy was observed by confocal immunofluorescence microscopy, localization analysis, and electron microscopy.
Results
EA treatment shortened the first black stool defecation time, increased the number, weight, and water content of 8-h feces, and improved the intestinal transit rate in FC mice (
P
<0.01). In terms of a putative autophagy mechanism, EA treatment promoted the expressions of LC3 and Beclin-1 proteins in the colonic tissue of FC mice (
P
<0.05), with glial fibrillary acidic protein (GFAP) and LC3 significantly colocalized. Furthermore, EA promoted colonic autophagy in FC mice by inhibiting PI3K/AKT/mTOR signaling (
P
<0.05 or
P
<0.01). The positive effect of EA on intestinal motility in FC mice was blocked by 3-MA.
Conclusion
EA treatment can inhibit PI3K/AKT/mTOR signaling in the colonic tissues of FC mice, thereby promoting EGCs autophagy to improve intestinal motility.</description><identifier>ISSN: 1672-0415</identifier><identifier>EISSN: 1993-0402</identifier><identifier>DOI: 10.1007/s11655-023-3594-3</identifier><identifier>PMID: 36973529</identifier><language>eng</language><publisher>Singapore: Springer Nature Singapore</publisher><subject>Acupuncture Research ; Animals ; Autophagy ; Beclin-1 ; Constipation - therapy ; Electroacupuncture ; Mammals - metabolism ; Medicine ; Medicine & Public Health ; Mice ; Neuroglia - metabolism ; Phosphatidylinositol 3-Kinases - metabolism ; Proto-Oncogene Proteins c-akt - metabolism ; Signal Transduction ; TOR Serine-Threonine Kinases - metabolism</subject><ispartof>Chinese journal of integrative medicine, 2023-05, Vol.29 (5), p.459-469</ispartof><rights>The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature 2023</rights><rights>2023. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c344t-50f7462a94031d9db0825085eaf9b82567df76bccf51ac63efe615af3af4d163</citedby><cites>FETCH-LOGICAL-c344t-50f7462a94031d9db0825085eaf9b82567df76bccf51ac63efe615af3af4d163</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11655-023-3594-3$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11655-023-3594-3$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27922,27923,41486,42555,51317</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36973529$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Lu</creatorcontrib><creatorcontrib>Chen, Ying</creatorcontrib><creatorcontrib>Xu, Ming-min</creatorcontrib><creatorcontrib>Cao, Wei</creatorcontrib><creatorcontrib>Zheng, Qian-hua</creatorcontrib><creatorcontrib>Zhou, Si-yuan</creatorcontrib><creatorcontrib>Yao, Jun-peng</creatorcontrib><creatorcontrib>Xi, Meng-han</creatorcontrib><creatorcontrib>Qin, Hai-yan</creatorcontrib><creatorcontrib>Li, Ying</creatorcontrib><creatorcontrib>Zhang, Wei</creatorcontrib><title>Electroacupuncture Alleviates Functional Constipation in Mice by Activating Enteric Glial Cell Autophagy via PI3K/AKT/mTOR Signaling</title><title>Chinese journal of integrative medicine</title><addtitle>Chin. J. Integr. Med</addtitle><addtitle>Chin J Integr Med</addtitle><description>Objective
To investigate autophagy-related mechanisms of electroacupuncture (EA) action in improving gastrointestinal motility in mice with functional constipation (FC).
Methods
According to a random number table, the Kunming mice were divided into the normal control, FC and EA groups in Experiment I. The autophagy inhibitor 3-methyladenine (3-MA) was used to observe whether it antagonized the effects of EA in Experiment II. An FC model was established by diphenoxylate gavage. Then the mice were treated with EA stimulation at Tianshu (ST 25) and Shangjuxu (ST 37) acupoints. The first black stool defecation time, the number, weight, and water content of 8-h feces, and intestinal transit rate were used to assess intestinal transit. Colonic tissues underwent histopathological assessment, and the expressions of autophagy markers microtubule-associated protein 1 light chain 3 (LC3) and Beclin-1 were detected by immunohistochemical staining. The expressions of phosphoinositide 3-kinases (PI3K)-protein kinase B (AKT)-mammalian target of rapamycin (mTOR) signaling pathway members were investigated by Western blot and quantitative reverse transcription-polymerase chain reaction, respectively. The relationship between enteric glial cells (EGCs) and autophagy was observed by confocal immunofluorescence microscopy, localization analysis, and electron microscopy.
Results
EA treatment shortened the first black stool defecation time, increased the number, weight, and water content of 8-h feces, and improved the intestinal transit rate in FC mice (
P
<0.01). In terms of a putative autophagy mechanism, EA treatment promoted the expressions of LC3 and Beclin-1 proteins in the colonic tissue of FC mice (
P
<0.05), with glial fibrillary acidic protein (GFAP) and LC3 significantly colocalized. Furthermore, EA promoted colonic autophagy in FC mice by inhibiting PI3K/AKT/mTOR signaling (
P
<0.05 or
P
<0.01). The positive effect of EA on intestinal motility in FC mice was blocked by 3-MA.
Conclusion
EA treatment can inhibit PI3K/AKT/mTOR signaling in the colonic tissues of FC mice, thereby promoting EGCs autophagy to improve intestinal motility.</description><subject>Acupuncture Research</subject><subject>Animals</subject><subject>Autophagy</subject><subject>Beclin-1</subject><subject>Constipation - therapy</subject><subject>Electroacupuncture</subject><subject>Mammals - metabolism</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mice</subject><subject>Neuroglia - metabolism</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Signal Transduction</subject><subject>TOR Serine-Threonine Kinases - metabolism</subject><issn>1672-0415</issn><issn>1993-0402</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kDtPwzAUhS0EgvL4ASzII0uoH7FTj1HVlooiEHS3HMcuRmkS7KRSd344jloYme651-ccWR8Atxg9YISyccCYM5YgQhPKRJrQEzDCQtAEpYicRs0zEjVmF-AyhE-EWMYROwcXlIuMMiJG4HtWGd35Rum-7Wvd9d7AvKrMzqnOBDgfbq6pVQWnTR0616phha6Gz04bWOxhHg27eK03cFZ3xjsNF5UbAqaqYN53TfuhNnsYG-Hrkj6N86f1eLt-eYPvbhOLY_AanFlVBXNznFdgPZ-tp4_J6mWxnOarRNM07RKGbJZyokSKKC5FWaAJYWjCjLKiiJJnpc14obVlWGlOjTUcM2WpsmmJOb0C94fa1jdfvQmd3Lqg4y9VbZo-SDJBmSApmohoxQer9k0I3ljZerdVfi8xkgN7eWAvI3s5sJc0Zu6O9X2xNeVf4hd2NJCDIcSnemO8_Gx6HxGEf1p_AM1mkEE</recordid><startdate>20230501</startdate><enddate>20230501</enddate><creator>Wang, Lu</creator><creator>Chen, Ying</creator><creator>Xu, Ming-min</creator><creator>Cao, Wei</creator><creator>Zheng, Qian-hua</creator><creator>Zhou, Si-yuan</creator><creator>Yao, Jun-peng</creator><creator>Xi, Meng-han</creator><creator>Qin, Hai-yan</creator><creator>Li, Ying</creator><creator>Zhang, Wei</creator><general>Springer Nature Singapore</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20230501</creationdate><title>Electroacupuncture Alleviates Functional Constipation in Mice by Activating Enteric Glial Cell Autophagy via PI3K/AKT/mTOR Signaling</title><author>Wang, Lu ; Chen, Ying ; Xu, Ming-min ; Cao, Wei ; Zheng, Qian-hua ; Zhou, Si-yuan ; Yao, Jun-peng ; Xi, Meng-han ; Qin, Hai-yan ; Li, Ying ; Zhang, Wei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c344t-50f7462a94031d9db0825085eaf9b82567df76bccf51ac63efe615af3af4d163</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Acupuncture Research</topic><topic>Animals</topic><topic>Autophagy</topic><topic>Beclin-1</topic><topic>Constipation - therapy</topic><topic>Electroacupuncture</topic><topic>Mammals - metabolism</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Mice</topic><topic>Neuroglia - metabolism</topic><topic>Phosphatidylinositol 3-Kinases - metabolism</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Signal Transduction</topic><topic>TOR Serine-Threonine Kinases - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Lu</creatorcontrib><creatorcontrib>Chen, Ying</creatorcontrib><creatorcontrib>Xu, Ming-min</creatorcontrib><creatorcontrib>Cao, Wei</creatorcontrib><creatorcontrib>Zheng, Qian-hua</creatorcontrib><creatorcontrib>Zhou, Si-yuan</creatorcontrib><creatorcontrib>Yao, Jun-peng</creatorcontrib><creatorcontrib>Xi, Meng-han</creatorcontrib><creatorcontrib>Qin, Hai-yan</creatorcontrib><creatorcontrib>Li, Ying</creatorcontrib><creatorcontrib>Zhang, Wei</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Chinese journal of integrative medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Lu</au><au>Chen, Ying</au><au>Xu, Ming-min</au><au>Cao, Wei</au><au>Zheng, Qian-hua</au><au>Zhou, Si-yuan</au><au>Yao, Jun-peng</au><au>Xi, Meng-han</au><au>Qin, Hai-yan</au><au>Li, Ying</au><au>Zhang, Wei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Electroacupuncture Alleviates Functional Constipation in Mice by Activating Enteric Glial Cell Autophagy via PI3K/AKT/mTOR Signaling</atitle><jtitle>Chinese journal of integrative medicine</jtitle><stitle>Chin. J. Integr. Med</stitle><addtitle>Chin J Integr Med</addtitle><date>2023-05-01</date><risdate>2023</risdate><volume>29</volume><issue>5</issue><spage>459</spage><epage>469</epage><pages>459-469</pages><issn>1672-0415</issn><eissn>1993-0402</eissn><abstract>Objective
To investigate autophagy-related mechanisms of electroacupuncture (EA) action in improving gastrointestinal motility in mice with functional constipation (FC).
Methods
According to a random number table, the Kunming mice were divided into the normal control, FC and EA groups in Experiment I. The autophagy inhibitor 3-methyladenine (3-MA) was used to observe whether it antagonized the effects of EA in Experiment II. An FC model was established by diphenoxylate gavage. Then the mice were treated with EA stimulation at Tianshu (ST 25) and Shangjuxu (ST 37) acupoints. The first black stool defecation time, the number, weight, and water content of 8-h feces, and intestinal transit rate were used to assess intestinal transit. Colonic tissues underwent histopathological assessment, and the expressions of autophagy markers microtubule-associated protein 1 light chain 3 (LC3) and Beclin-1 were detected by immunohistochemical staining. The expressions of phosphoinositide 3-kinases (PI3K)-protein kinase B (AKT)-mammalian target of rapamycin (mTOR) signaling pathway members were investigated by Western blot and quantitative reverse transcription-polymerase chain reaction, respectively. The relationship between enteric glial cells (EGCs) and autophagy was observed by confocal immunofluorescence microscopy, localization analysis, and electron microscopy.
Results
EA treatment shortened the first black stool defecation time, increased the number, weight, and water content of 8-h feces, and improved the intestinal transit rate in FC mice (
P
<0.01). In terms of a putative autophagy mechanism, EA treatment promoted the expressions of LC3 and Beclin-1 proteins in the colonic tissue of FC mice (
P
<0.05), with glial fibrillary acidic protein (GFAP) and LC3 significantly colocalized. Furthermore, EA promoted colonic autophagy in FC mice by inhibiting PI3K/AKT/mTOR signaling (
P
<0.05 or
P
<0.01). The positive effect of EA on intestinal motility in FC mice was blocked by 3-MA.
Conclusion
EA treatment can inhibit PI3K/AKT/mTOR signaling in the colonic tissues of FC mice, thereby promoting EGCs autophagy to improve intestinal motility.</abstract><cop>Singapore</cop><pub>Springer Nature Singapore</pub><pmid>36973529</pmid><doi>10.1007/s11655-023-3594-3</doi><tpages>11</tpages></addata></record> |
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| language | eng |
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| source | MEDLINE; Alma/SFX Local Collection; SpringerLink Journals - AutoHoldings |
| subjects | Acupuncture Research Animals Autophagy Beclin-1 Constipation - therapy Electroacupuncture Mammals - metabolism Medicine Medicine & Public Health Mice Neuroglia - metabolism Phosphatidylinositol 3-Kinases - metabolism Proto-Oncogene Proteins c-akt - metabolism Signal Transduction TOR Serine-Threonine Kinases - metabolism |
| title | Electroacupuncture Alleviates Functional Constipation in Mice by Activating Enteric Glial Cell Autophagy via PI3K/AKT/mTOR Signaling |
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