Article(id=1236344968403538108, tenantId=1146029695717560320, journalId=1235980733773295621, issueId=1236344966058931117, articleNumber=null, orderNo=null, doi=null, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=null, receivedDateStr=null, revisedDate=null, revisedDateStr=null, acceptedDate=1655654400000, acceptedDateStr=2022-06-20, onlineDate=1772697210645, onlineDateStr=2026-03-05, pubDate=1678809600000, pubDateStr=2023-03-15, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1772697210645, onlineIssueDateStr=2026-03-05, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1772697210645, creator=13701087609, updateTime=1772697210645, updator=13701087609, issue=Issue{id=1236344966058931117, tenantId=1146029695717560320, journalId=1235980733773295621, year='2023', volume='32', issue='5', pageStart='441', pageEnd='552', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1772697210087, creator=13701087609, updateTime=1772697640190, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1236346770087793082, tenantId=1146029695717560320, journalId=1235980733773295621, issueId=1236344966058931117, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1236346770087793083, tenantId=1146029695717560320, journalId=1235980733773295621, issueId=1236344966058931117, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=513, endPage=521, ext={EN=ArticleExt(id=1236344968634224837, articleId=1236344968403538108, tenantId=1146029695717560320, journalId=1235980733773295621, language=EN, title=β-Caryophyllene reduces cerebral ischemia-reperfusion injury in rats by activating HSF1/HSP70 pathway, columnId=null, journalTitle=Chinese Journal of New Drugs, columnName=null, runingTitle=null, highlight=null, articleAbstract=
Objective: To investigate whether β-caryophyllene (BCP) can reduce cerebral ischemia-reperfusion injury (CIR) in rats via activating heat shock factor 1 (HSF1)/heat shock protein 70 (HSP70) pathway.
Methods: Male SD rats were randomly assigned to the sham operation group, model group, BCP low, medium, and high dose groups (204,306,408 mg·kg-1), BCP (306 mg·kg-1)+Kribb11 intervention group, and Kribb11 intervention group. The suture method was used to create a rat model of CIR injury, and the neurobehavioral score was recorded 24 hours after the reperfusion. The volume of the cerebral infarct was measured using 2,3,5-triphenyltetrazolium chloride staining, and the pathological changes of cortical neurons were observed using hematoxylin-eosin staining and Nissl staining. Western blotting was applied to detect protein expressions of HSP70, HSF1, p-HSF1, Chop, Caspase 3, Bcl2, and Bax in rat brain cortex; immunofluorescence staining was used to detect protein expressions of p-HSF1 and HSP70; and Tunel staining to evaluate cell apoptosis level. Malondialdehyde level in cortical tissue (MDA), activities of total superoxide dismutase (SOD) and Caspase 3 were measured using a chemical colorimetric technique.
Results: Compared to the model group, the β-caryophyllene administration group indicated a lower cerebral infarct volume in rats (P<0.01), a lower level of MDA and Caspase 3 activity in the tissue (P<0.01,P<0.05), a decreased expression of Bax, Chop, and Caspase 3 protein (P<0.01), a decreased occurrence of cell apoptosis, and increased protein expressions of HSF1, p-HSF1, HSP70, and Bcl 2 in the tissue (P<0.01), and substantially greater SOD activity in the tissue (P<0.01), reducing ischemia-reperfusion injury. Compared with the BCP group, Kribb11 in the BCP+Kribb11 group antagonized the curative effect of BCP, the protein expressions of HSF1, p-HSF1 and HSP70 were significantly reduced (P<0.05, P<0.01), and tissue oxidation stress levels increased, cortical cell death increased, and ischemia-reperfusion injury aggravated.
Conclusion: In rats, β-caryophyllene can alleviate cerebral ischemia-reperfusion injury in rats by reducing oxidative stress and minimizing cell apoptosis, which is associated with the activation of the HSF1/HSP70 pathway.
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目的： 探究β-石竹烯（β-caryophyllene, BCP）通过激活热休克转录因子1（heat shock factor 1, HSF1）/热休克蛋白70（heat shock proteins 70, HSP70）通路减轻大鼠脑缺血再灌注（cerebral ischemia-reperfusion, CIR）损伤的机制。
方法： 将雄性SD大鼠随机分为假手术组、模型组、BCP低、中、高剂量组（204，306，408 mg·kg-1）、BCP（306 mg·kg-1）+Kribb11组和Kribb11组。采用线栓法建立大鼠CIR模型，再灌注24 h后进行神经行为学评分；2，3，5-三苯基氯化四氮唑染色法测定脑梗死体积；苏木精-伊红染色、尼式染色观察皮层神经元病理变化；蛋白印迹法检测大鼠脑皮层中HSP70，HSF1，p-HSF1和凋亡相关蛋白（Chop，Caspase 3，Bcl2，Bax）的蛋白表达；免疫荧光染色检测p-HSF1和HSP70蛋白表达；Tunel染色检测细胞凋亡水平；化学比色法检测皮层组织中丙二醛（MDA）含量和总超氧化物歧化酶（SOD）及Caspase 3活性。
结果： 与模型组相比，BCP组大鼠脑梗死体积明显降低（P<0.01），组织中HSF1，p-HSF1，HSP70和Bcl2蛋白表达显著增加（P<0.01），Bax，Chop，Caspase 3蛋白表达均明显减少（P<0.01），组织中MDA含量减少（P<0.01）和SOD的活性增加（P<0.01），Caspase 3酶活性显著降低（P<0.05），细胞凋亡减少，从而改善了缺血再灌注损伤；与BCP组相比，BCP+Kribb11组中Kribb11拮抗了BCP的疗效作用，HSF1，p-HSF1和HSP70蛋白表达显著减少（P<0.05，P<0.01），组织氧化应激水平升高，皮层细胞死亡增多，CIR损伤加重。
结论： BCP能够降低氧化应激水平，抑制细胞凋亡，从而改善大鼠CIR损伤，其机制可能与激活HSF1/HSP70通路有关。
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左天睿，男，硕士研究生，主要从事神经药理学研究。E-mail: 405852908@qq.com。
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左天睿，男，硕士研究生，主要从事神经药理学研究。E-mail: 405852908@qq.com。
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