Article(id=1292130369487266780, tenantId=1146029695717560320, journalId=1246415772164075586, issueId=1292130254689165893, articleNumber=null, orderNo=null, doi=10.13699/j.cnki.1001-6821.2026.05.012, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1768147200000, receivedDateStr=2026-01-12, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1785997486707, onlineDateStr=2026-08-06, pubDate=1773676800000, pubDateStr=2026-03-17, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1785997486707, onlineIssueDateStr=2026-08-06, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1785997486707, creator=13701087609, updateTime=1785997486707, updator=13701087609, issue=Issue{id=1292130254689165893, tenantId=1146029695717560320, journalId=1246415772164075586, year='2026', volume='42', issue='5', pageStart='601', pageEnd='750', issueExtLink='null', onlineDate='null', pubDate='1773676800000', pubDateStr='2026-03-17', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1785997459337, creator='13701087609', updateTime=1786014469153, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1292201599108141219, tenantId=1146029695717560320, journalId=1246415772164075586, issueId=1292130254689165893, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1292201599108141220, tenantId=1146029695717560320, journalId=1246415772164075586, issueId=1292130254689165893, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=664, endPage=670, ext={EN=ArticleExt(id=1292130369730536413, articleId=1292130369487266780, tenantId=1146029695717560320, journalId=1246415772164075586, language=EN, title=Research of mechanism of nobiletin improving slow transit constipation in rats by downregulating
DRD2 based on the AMPK/eNOS signaling pathway, columnId=1246531407326105792, journalTitle=Chinese Journal of Clinical Pharmacology, columnName=Clinical and Basic Bridging Research, runingTitle=null, highlight=null, articleAbstract=
Objective To investigate the effects and mechanism of nobiletin (NOB) on slow transit constipation (STC) in rats through dopamine receptor D2 (DRD2).
Methods A total of 70 SD rats were randomly divided into blank group, model group, experimental-L, M, H group, AAV9-NC group and AAV9-DRD2 group, with 10 rats in each group. STC model was established with 15 mg·kg-1 compound diphenoxylate by intragastric administration except in blank group. In experimental-L, M, H group, 0.1, 0.2, 0.4 g·kg-1 NOB was administered intragastricly. On the basis of experimental-M group, AAV9-NC group and AAV9-DRD2 group were given AAV9-NC and AAV9-DRD2 100 μL, respectively. Weight and fecal indexes of rats were detected. The expression levels of DRD2 was detected by quantitative real time polymerase chain reaction. Vasoactive intestinal peptide (VIP) and nitric oxide (NO) levels were detected by enzyme-linked immunosorbent assay. Levels of AMP-activated protein kinase (AMPK)/endothelial nitric oxide synthase (eNOS) signaling pathway related proteins were detected by Western blot.
Results The fecal water content in blank, model, and experimental-L, M, H groups were (35.24±5.25)%, (24.76±3.47)%, (28.38±2.77)%, (32.76±3.49)% and (33.32±4.34)% , respectively; the fecal quantity were (53.20±5.25), (42.40±4.55), (47.10±5.36), (49.50±5.10) and (50.10±5.04) grains, respectively. Compared model group with blank group, and compared experimental-L, -M, -H groups with model group, the above indicators showed statistically significant differences (P<0.05, P<0.01, P<0.001). The relative expression levels of DRD2 mRNA in blank, model and experimental-L, M, H groups were 1.00±0.12, 2.95±0.47, 2.73±0.49, 2.17±0.35 and 2.08±0.32, respectively. The relative expression levels of DRD2 mRNA in the experimental-M and experimental-H groups were significantly lower than those in the model group (all P<0.001), with no significant difference between the two groups (P>0.05); therefore, experimental-M was selected for subsequent experiments. The VIP levels of blank group, model group, experimental-M group, AAV9-NC group and AAV9-DRD2 group were (43.15±4.52), (64.42±7.64), (51.68±5.37), (49.25±4.44) and (56.84±6.41) ng·L-1, respectively; NO levels were (6.84±0.71), (11.68±1.37), (9.28±0.93), (9.35±0.97) and (10.45±1.03) μmol·L-1, respectively; the relative expression levels of AMPK protein were 1.00±0.15, 2.42±0.34, 1.68±0.17, 1.55±0.18 and 1.94±0.21, respectively; the relative expression levels of eNOS protein were 1.00±0.11, 3.18±0.35, 2.28±0.23, 2.35±0.27 and 2.95±0.33, respectively. Compared model group with blank group, compared experimental-M group with model group, and compared AAV9-DRD2 group with AAV9-NC group, the above indicators all showed statistically significant differences (all P<0.05).
Conclusion NOB can improve STC in rats, possibly by down-regulating DRD2 expression, regulating VIP and NO levels, and inhibiting the AMPK/eNOS signaling pathway.
, authors=Xiao-guang WEI, Quan WANG, Wen-juan SUN, Min LI, Ling CHENG, authorsList=Xiao-guang WEI, Quan WANG, Wen-juan SUN, Min LI, Ling CHENG, authorCompany=null, correspAuthors=Quan WANG, 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=1292130370145772511, articleId=1292130369487266780, tenantId=1146029695717560320, journalId=1246415772164075586, language=CN, title=川陈皮素基于AMPK/eNOS信号通路通过下调
DRD2改善大鼠慢传输型便秘的作用机制研究, columnId=1246531407485489349, journalTitle=中国临床药理学杂志, columnName=临床与基础桥接研究, runingTitle=null, highlight=null, articleAbstract=
目的 探讨川陈皮素（NOB）通过多巴胺受体D2（DRD2）对慢传输型便秘（STC）大鼠的作用及其机制。
方法 70只SD大鼠随机分为空白组、模型组、低、中、高剂量实验组、AAV9-NC组和AAV9-DRD2组，每组10只。除空白组外，各组均用15 mg·kg-1复方地芬诺酯灌胃建立STC模型。低、中、高剂量实验组分别用0.1、0.2、0.4 g·kg-1 NOB灌胃，AAV9-NC组和AAV9-DRD2组在中剂量实验组基础上分别给予尾静脉注射AAV9-NC和AAV9-DRD2 100 μL。检测大鼠体质量和粪便指标，用实时定量反转录聚合酶链式反应检测DRD2表达水平，用酶联免疫吸附实验法检测血管活性肠肽（VIP）和一氧化氮（NO）水平，用蛋白质印迹法检测腺苷酸活化蛋白激酶（AMPK）/内皮型一氧化氮合酶（eNOS）信号通路相关蛋白水平。
结果 空白组、模型组和低、中、高剂量实验组的粪便含水量分别为（35.24±5.25）%、（24.76±3.47）%、（28.38±2.77）%、（32.76±3.49）%和（33.32±4.34）%；粪便数量分别为（53.20±5.25）、（42.40±4.55）、（47.10±5.36）、（49.50±5.10）和（50.10±5.04）粒；模型组与空白组比较，低、中、高剂量实验组与模型组比较，上述指标在统计学上差异均有统计学意义（P<0.05，P<0.01，P<0.001）。DRD2 mRNA的相对表达水平分别为1.00±0.12、2.95±0.47、2.73±0.49、2.17±0.35和2.08±0.32，中、高剂量实验组的DRD2 mRNA相对表达水平较模型组均显著降低（均P<0.001），但2者比较在统计学上差异无统计学意义（P>0.05），故选用中剂量实验组进行后续实验。空白组、模型组、中剂量实验组、AAV9-NC组和AAV9-DRD2组VIP水平分别为（43.15±4.52）、（64.42±7.64）、（51.68±5.37）、（49.25±4.44）和（56.84±6.41）ng·L-1，NO水平分别为（6.84±0.71）、（11.68±1.37）、（9.28±0.93）、（9.35±0.97）和（10.45±1.03）μmol·L-1，AMPK蛋白相对表达水平分别为1.00±0.15、2.42±0.34、1.68±0.17、1.55±0.18和1.94±0.21，eNOS蛋白相对表达水平分别为1.00±0.11、3.18±0.35、2.28±0.23、2.35±0.27和2.95±0.33，模型组与空白组比较，中剂量实验组与模型组比较，AAV9-DRD2组与AAV9-NC组比较，上述指标在统计学上差异均有统计学意义（均P<0.05）。
结论 NOB能够改善大鼠STC，可能是通过下调DRD2表达，调节VIP和NO水平，抑制AMPK/eNOS信号通路实现的。
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魏晓广（1981-），男，副主任中医师，主要从事中西医结合消化病方面的工作和研究
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