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Article(id=1291753164374561171, tenantId=1146029695717560320, journalId=1291416913693474840, issueId=1291753151179280707, articleNumber=PA20260408_KEFmt6VB, orderNo=null, doi=10.3969/j.issn.1671-7856.2026.06.005, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1751212800000, receivedDateStr=2025-06-30, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1785907554000, onlineDateStr=2026-08-05, pubDate=1774800000000, pubDateStr=2026-03-30, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1785907554000, onlineIssueDateStr=2026-08-05, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1785907554000, creator=admin, updateTime=1785907554000, updator=admin, issue=Issue{id=1291753151179280707, tenantId=1146029695717560320, journalId=1291416913693474840, year='2026', volume='36', issue='6', pageStart='1', pageEnd='144', issueExtLink='null', onlineDate='null', pubDate='1774800000000', pubDateStr='2026-03-30', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=1, specialIssue=null, createTime=1785907550854, creator='ztmeta', updateTime=1786331902788, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1293533012289941791, tenantId=1146029695717560320, journalId=1291416913693474840, issueId=1291753151179280707, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1293533012289941792, tenantId=1146029695717560320, journalId=1291416913693474840, issueId=1291753151179280707, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=41, endPage=50, ext={EN=ArticleExt(id=1291753172914164122, articleId=1291753164374561171, tenantId=1146029695717560320, journalId=1291416913693474840, language=EN, title=Possible mechanisms underlying improvement of autism-like behaviors by melanocortin receptor agonists in Shank3-deficient rats, columnId=1292760394137887571, journalTitle=Chinese Journal of Comparative Medicine, columnName=Reseaech Reports, runingTitle=null, highlight=null, articleAbstract=
Objective

To explore the mechanism by which melanotan-II (MT-II) improves social deficits in a Shank3 gene-deficient autism model.

Methods

Rats were divided into control and Shank3-deficient model groups (n = 18 per group) treated by microinjection of empty or Shank3-interfering lentivirus, respectively, into the right lateral ventricle of neonatal rats. Shank3-deficient rats were further divided randomly into two groups: Shank3+saline (Sh3-Sal) and Shank3+ MT-II (Sh3-MT-II) groups (n = 9 per group). Similarly, control rats were divided into control+saline (V-Sal) and control+MT-II (V-MT-II) groups (n=9 per group). On day 28, rats in the V-MT-II and Sh3-MT-II groups received intraperitoneal (i. p.) injections of MT-II (3.3 mg/kg), while rats in the V-Sal and Sh3-Sal groups received i. p. saline (3.3 mL/kg). Behavioral changes were assessed using the open-field test, grooming behavior analysis, three-chamber social test, and the Morris water maze test. mRNA and protein expression levels of hypothalamic oxytocin (OXT), OXT receptor (OXTR), and melanocortin receptor 4 (MC4R) were detected by reverse transcription-polymerase chain reaction and Western blot, respectively.

Results

In the three-chamber social test, Sh3-Sal group rats showed no significant social preference compared with the time spent with stranger rat 1 (P>0.05). In contrast, after MT-II intervention, Sh3-MT-II group rats spent significantly longer with stranger rat 2 (P<0.01). In the Morris water maze test, rats in the Sh3-Sal group exhibited significant learning and memory impairments compared with the V-Sal group (P<0.05), while MT-II intervention significantly improved the learning and memory performance of the Sh3-MT-II group (P<0.01). The open field and grooming tests revealed that Sh3-Sal group rats spent significantly longer in the peripheral zone of the open field and exhibited increased grooming behavior compared with the V-Sal group (P<0.01). However, MT-II did not significantly alter the center time or self-grooming behavior compared with the Sh3-Sal group (P>0.05). mRNA expression levels of OXT, OXTR, and MC4R were significantly higher in the Sh3-MT-II group than in the Sh3-Sal group (P<0.05,P<0.01). Hypothalamic OXT protein expression was significantly increased in the Sh3-MT-II group compared with the Sh3-Sal group (P<0.05), while hypothalamic SHANK3 protein expression was significantly decreased in both the Sh3-Sal and Sh3-MT-II groups compared with the V-Sal group (P<0.05,P<0.01), and protein expression levels of OXTR and MC4R showed no significant changes (P>0.05).

Conclusions

The melanocortin receptor agonist MT-II may ameliorate social deficits in Shank3-deficient autistic rats by activating the hypothalamic OXT system. This suggests that targeting the OXT/MC4R pathway could be a potential therapeutic strategy for social deficits in patients with autism spectrum disorder.

, authors=Xiaofang CHEN1, Juan WANG2, Ping OU3, Sijie CHEN3, *, Longsheng HUANG1, 3, *, authorsList=Xiaofang CHEN, Juan WANG, Ping OU, Sijie CHEN, Longsheng HUANG, authorCompany=null, correspAuthors=Sijie CHEN, Longsheng HUANG, authorNote=null, correspAuthorsNote=null, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1291753172830278041, articleId=1291753164374561171, tenantId=1146029695717560320, journalId=1291416913693474840, language=CN, title=黑皮质素受体激动剂改善Shank3基因缺陷孤独症模型大鼠行为的机制研究, columnId=1292760394347606213, journalTitle=中国比较医学杂志, columnName=研究报告, runingTitle=null, highlight=null, articleAbstract=
目的

探讨黑皮质素受体激动剂（MT-II）改善SH3和多个锚蛋白重复结构域3（Shank3）基因缺陷孤独症模型鼠社交缺陷的作用机制。

方法

利用Shank3干扰慢病毒和空载慢病毒注射至仔鼠右侧脑室构建Shank3模型鼠和空载鼠各18只，Shank3组随机分为Shank3+Sal（Sh3-Sal）组9只和Shank3+MT-II（Sh3-MT-II）组9只，空载组随机分为空载+Sal（V-Sal）组9只和空载+MT-II（V-MT-II）组9只。V-MT-II组和Sh3-MT-II组于第28天腹腔注射3.3 mL/kg MT-II，V-Sal组和Sh3-Sal组腹腔注射3.3 mL/kg 0.9%氯化钠溶液，通过旷场实验、理毛实验、三箱社交实验及Morris水迷宫实验评估其行为学改变；采用逆转录聚合酶链式反应（RT-PCR）和蛋白免疫印迹（Western blot）检测下丘脑催产素（OXT）、催产素受体（OXTR）及黑皮质素受体4（MC4R）的mRNA与蛋白表达水平。

结果

行为学结果显示，三箱社交实验中与陌生鼠1相比，Sh3-Sal组未表现出社交差异（P>0.05），而MT-II干预后，Sh3-MT-II组与陌生鼠2的社交时间显著增加，差异有统计学意义（P<0.01）。Morris水迷宫实验中与V-Sal组相比，Sh3-Sal组表现出显著的学习记忆障碍（P<0.05），而MT-II干预后，Sh3-MT-II组学习记忆能力明显提高，差异有统计学意义（P<0.01）。旷场实验和理毛实验结果显示，与V-Sal组相比，Sh3-Sal组周边停留时间及理毛时间均显著增加，差异有统计学意义（P<0.01）；MT-II干预后，旷场中心停留时间及理毛行为与Sh3-Sal组无显著差异（P>0.05）。RT-PCR检测显示，与Sh3-Sal组相比，Sh3-MT-II组OXT、OXTR和MC4R mRNA表达水平明显升高，差异有统计学意义（P<0.05）；Western blot法检测显示，与Sh3-Sal组相比，Sh3-MT-II组大鼠下丘脑OXT蛋白表达水平明显升高（P<0.05），与V-Sal组相比，Sh3-Sal组和Sh3-MT-II组大鼠下丘脑SHANK3蛋白表达水平明显降低（P<0.05，P<0.01），而OXTR及MC4R蛋白表达水平无显著差异（P>0.05）。

结论

黑皮质素受体激动剂MT-II可能通过激活下丘脑OXT系统改善Shank3缺陷孤独症模型鼠的社交障碍，提示靶向OXT/MC4R通路或为孤独症社交缺陷的潜在干预策略。

, authors=陈晓芳1, 王娟2, 欧萍3, 陈思洁3, *, 黄龙生1, 3, *, authorsList=陈晓芳, 王娟, 欧萍, 陈思洁, 黄龙生, authorCompany=null, correspAuthors=陈思洁, 黄龙生, authorNote=

#

共同第一作者

*

陈晓芳（1985—），女，硕士，主治医师，研究方向：孤独症的诊断与治疗研究。E-mail:

王娟（1998—），女，在读博士研究生，研究方向：孤独症的诊断与治疗研究。E-mail:

, correspAuthorsNote=
陈思洁（1996—），女，硕士，住院医师，研究方向：孤独症诊治及康复。E-mail:
黄龙生（1983—），男，博士，副主任医师，研究方向：孤独症的康复研究。E-mail:
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黑皮质素受体激动剂改善Shank3基因缺陷孤独症模型大鼠行为的机制研究
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陈晓芳 1 , 王娟 2 , 欧萍 3 , 陈思洁 3, * , 黄龙生 1, 3, *
中国比较医学杂志 | 研究报告 2026,36(6): 41-50
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中国比较医学杂志 |研究报告 2026 , 36 (6) : 41 -50
黑皮质素受体激动剂改善Shank3基因缺陷孤独症模型大鼠行为的机制研究
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陈晓芳（1985—），女，硕士，主治医师，研究方向：孤独症的诊断与治疗研究。E-mail:

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陈晓芳（1985—），女，硕士，主治医师，研究方向：孤独症的诊断与治疗研究。E-mail:

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王娟（1998—），女，在读博士研究生，研究方向：孤独症的诊断与治疗研究。E-mail:

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王娟（1998—），女，在读博士研究生，研究方向：孤独症的诊断与治疗研究。E-mail:

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陈晓芳1 , 王娟2 , 欧萍3, 陈思洁3, * , 黄龙生1, 3, *
作者信息
  • 1．晋江市妇幼保健院，福建 泉州　362200
  • 2．福建医科大学，福州　351022
  • 3．福建省妇幼保健院，福州　350001
通讯作者:
陈思洁（1996—），女，硕士，住院医师，研究方向：孤独症诊治及康复。E-mail:
黄龙生（1983—），男，博士，副主任医师，研究方向：孤独症的康复研究。E-mail:
作者简介:

#

共同第一作者

*

陈晓芳（1985—），女，硕士，主治医师，研究方向：孤独症的诊断与治疗研究。E-mail:

王娟（1998—），女，在读博士研究生，研究方向：孤独症的诊断与治疗研究。E-mail:

Possible mechanisms underlying improvement of autism-like behaviors by melanocortin receptor agonists in Shank3-deficient rats
Xiaofang CHEN1 , Juan WANG2 , Ping OU3, Sijie CHEN3, * , Longsheng HUANG1, 3, *
Affiliations
  • 1.Jinjiang Maternal and Child Health Hospital, Quanzhou 362200, China
  • 2.Fujian Medical University, Fuzhou 351022
  • 3.Fujian Maternal and Child Health Hospital, Fuzhou 350001
出版时间: 2026-03-30 doi: 10.3969/j.issn.1671-7856.2026.06.005
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摘要
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目的

探讨黑皮质素受体激动剂（MT-II）改善SH3和多个锚蛋白重复结构域3（Shank3）基因缺陷孤独症模型鼠社交缺陷的作用机制。

方法

利用Shank3干扰慢病毒和空载慢病毒注射至仔鼠右侧脑室构建Shank3模型鼠和空载鼠各18只，Shank3组随机分为Shank3+Sal（Sh3-Sal）组9只和Shank3+MT-II（Sh3-MT-II）组9只，空载组随机分为空载+Sal（V-Sal）组9只和空载+MT-II（V-MT-II）组9只。V-MT-II组和Sh3-MT-II组于第28天腹腔注射3.3 mL/kg MT-II，V-Sal组和Sh3-Sal组腹腔注射3.3 mL/kg 0.9%氯化钠溶液，通过旷场实验、理毛实验、三箱社交实验及Morris水迷宫实验评估其行为学改变；采用逆转录聚合酶链式反应（RT-PCR）和蛋白免疫印迹（Western blot）检测下丘脑催产素（OXT）、催产素受体（OXTR）及黑皮质素受体4（MC4R）的mRNA与蛋白表达水平。

结果

行为学结果显示，三箱社交实验中与陌生鼠1相比，Sh3-Sal组未表现出社交差异（P>0.05），而MT-II干预后，Sh3-MT-II组与陌生鼠2的社交时间显著增加，差异有统计学意义（P<0.01）。Morris水迷宫实验中与V-Sal组相比，Sh3-Sal组表现出显著的学习记忆障碍（P<0.05），而MT-II干预后，Sh3-MT-II组学习记忆能力明显提高，差异有统计学意义（P<0.01）。旷场实验和理毛实验结果显示，与V-Sal组相比，Sh3-Sal组周边停留时间及理毛时间均显著增加，差异有统计学意义（P<0.01）；MT-II干预后，旷场中心停留时间及理毛行为与Sh3-Sal组无显著差异（P>0.05）。RT-PCR检测显示，与Sh3-Sal组相比，Sh3-MT-II组OXT、OXTR和MC4R mRNA表达水平明显升高，差异有统计学意义（P<0.05）；Western blot法检测显示，与Sh3-Sal组相比，Sh3-MT-II组大鼠下丘脑OXT蛋白表达水平明显升高（P<0.05），与V-Sal组相比，Sh3-Sal组和Sh3-MT-II组大鼠下丘脑SHANK3蛋白表达水平明显降低（P<0.05，P<0.01），而OXTR及MC4R蛋白表达水平无显著差异（P>0.05）。

结论

黑皮质素受体激动剂MT-II可能通过激活下丘脑OXT系统改善Shank3缺陷孤独症模型鼠的社交障碍，提示靶向OXT/MC4R通路或为孤独症社交缺陷的潜在干预策略。

孤独症谱系障碍  /  Shank3缺陷  /  黑皮质素受体激动剂  /  行为学  /  催产素
Objective

To explore the mechanism by which melanotan-II (MT-II) improves social deficits in a Shank3 gene-deficient autism model.

Methods

Rats were divided into control and Shank3-deficient model groups (n = 18 per group) treated by microinjection of empty or Shank3-interfering lentivirus, respectively, into the right lateral ventricle of neonatal rats. Shank3-deficient rats were further divided randomly into two groups: Shank3+saline (Sh3-Sal) and Shank3+ MT-II (Sh3-MT-II) groups (n = 9 per group). Similarly, control rats were divided into control+saline (V-Sal) and control+MT-II (V-MT-II) groups (n=9 per group). On day 28, rats in the V-MT-II and Sh3-MT-II groups received intraperitoneal (i. p.) injections of MT-II (3.3 mg/kg), while rats in the V-Sal and Sh3-Sal groups received i. p. saline (3.3 mL/kg). Behavioral changes were assessed using the open-field test, grooming behavior analysis, three-chamber social test, and the Morris water maze test. mRNA and protein expression levels of hypothalamic oxytocin (OXT), OXT receptor (OXTR), and melanocortin receptor 4 (MC4R) were detected by reverse transcription-polymerase chain reaction and Western blot, respectively.

Results

In the three-chamber social test, Sh3-Sal group rats showed no significant social preference compared with the time spent with stranger rat 1 (P>0.05). In contrast, after MT-II intervention, Sh3-MT-II group rats spent significantly longer with stranger rat 2 (P<0.01). In the Morris water maze test, rats in the Sh3-Sal group exhibited significant learning and memory impairments compared with the V-Sal group (P<0.05), while MT-II intervention significantly improved the learning and memory performance of the Sh3-MT-II group (P<0.01). The open field and grooming tests revealed that Sh3-Sal group rats spent significantly longer in the peripheral zone of the open field and exhibited increased grooming behavior compared with the V-Sal group (P<0.01). However, MT-II did not significantly alter the center time or self-grooming behavior compared with the Sh3-Sal group (P>0.05). mRNA expression levels of OXT, OXTR, and MC4R were significantly higher in the Sh3-MT-II group than in the Sh3-Sal group (P<0.05,P<0.01). Hypothalamic OXT protein expression was significantly increased in the Sh3-MT-II group compared with the Sh3-Sal group (P<0.05), while hypothalamic SHANK3 protein expression was significantly decreased in both the Sh3-Sal and Sh3-MT-II groups compared with the V-Sal group (P<0.05,P<0.01), and protein expression levels of OXTR and MC4R showed no significant changes (P>0.05).

Conclusions

The melanocortin receptor agonist MT-II may ameliorate social deficits in Shank3-deficient autistic rats by activating the hypothalamic OXT system. This suggests that targeting the OXT/MC4R pathway could be a potential therapeutic strategy for social deficits in patients with autism spectrum disorder.

autism spectrum disorder  /  Shank3-deficiency  /  melanocortin receptor agonist  /  behavior  /  oxytocin
陈晓芳, 王娟, 欧萍, 陈思洁, 黄龙生. 黑皮质素受体激动剂改善Shank3基因缺陷孤独症模型大鼠行为的机制研究. 中国比较医学杂志, 2026 , 36 (6) : 41 -50 . DOI: 10.3969/j.issn.1671-7856.2026.06.005
Xiaofang CHEN, Juan WANG, Ping OU, Sijie CHEN, Longsheng HUANG. Possible mechanisms underlying improvement of autism-like behaviors by melanocortin receptor agonists in Shank3-deficient rats[J]. Chinese Journal of Comparative Medicine, 2026 , 36 (6) : 41 -50 . DOI: 10.3969/j.issn.1671-7856.2026.06.005
基金
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  • 福建省科技创新联合资金项目(2024Y9578)
  • 福建省卫生健康重大科研专项(2024ZD01005)
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doi: 10.3969/j.issn.1671-7856.2026.06.005
  • 接收时间：2025-06-30
  • 首发时间：2026-08-05
  • 出版时间：2026-03-30
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  • 收稿日期：2025-06-30
基金
福建省科技创新联合资金项目(2024Y9578)
福建省卫生健康重大科研专项(2024ZD01005)
作者信息
    1．晋江市妇幼保健院，福建 泉州　362200
    2．福建医科大学，福州　351022
    3．福建省妇幼保健院，福州　350001

通讯作者:

陈思洁（1996—），女，硕士，住院医师，研究方向：孤独症诊治及康复。E-mail:
黄龙生（1983—），男，博士，副主任医师，研究方向：孤独症的康复研究。E-mail:
参考文献
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https://castjournals.cast.org.cn/joweb/zgbjyxzz/CN/10.3969/j.issn.1671-7856.2026.06.005
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鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
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