{"title":"姜黄素通过ERK-CHOP-caspase-11途径抑制大鼠脑缺血再灌注损伤和细胞凋亡。","authors":"Yue Chen, Lixia Zhang, Zengtai Yang, Jie Yu","doi":"10.1080/13880209.2022.2069271","DOIUrl":null,"url":null,"abstract":"<p><strong>Context: </strong>Curcumin has a significant effect on cerebral ischaemia-reperfusion injury (CIRI). However, the underlying mechanism is less studied.</p><p><strong>Objective: </strong>This study investigates the role and mechanism of curcumin in CIRI.</p><p><strong>Materials and methods: </strong>CIRI model Sprague-Dawley rats were divided into model, positive control and curcumin low/middle/high dose (50, 100 and 200 mg/kg/d) groups (<i>n</i> = 10 each). Drug intervention was administered by gavage once a day for 4 weeks. We calculated the neurobehavioural score and observed the cerebral infarct volume. Glial cytopathological changes were observed after haematoxylin-eosin staining. Apoptosis was detected by TUNEL (TdT mediated dUTP nick end labelling). Extracellular signal-regulated protein kinase (<i>ERK</i>), C/EBP-homologous protein (<i>CHOP</i>) and <i>caspase-11</i> mRNA were detected by real-time PCR. Phosphorylated ERK (p-ERK), phosphorylated CHOP (p-CHOP) and caspase-11 were detected by Western blot. Superoxide dismutase (SOD) activity was detected by xanthine oxidation method; malondialdehyde (MDA) content by thiobarbituric acid colorimetry; and, glutathione (GSH) by spectrophotometry.</p><p><strong>Results: </strong>Compared with control, the neurobehavioural scores, neuronal apoptosis, MDA, IL-1β, IL-18, mRNAs and protein levels of ERK/p-ERK, CHOP/p-CHOP and caspase-11 in model group were significantly higher (<i>p</i> < 0.01). Compared with model, the positive control and medium/high dose curcumin groups were significantly lower (<i>p</i> < 0.01). However, SOD and GSH decreased significantly in model group but increased significantly in positive control and medium/high dose curcumin groups (<i>p</i> < 0.01). Moreover, curcumin significantly alleviated ischaemic state and neuroinflammation (<i>p</i> < 0.01).</p><p><strong>Discussion and conclusions: </strong>Curcumin may alleviate CIRI through ERK-CHOP-caspase-11 pathway. Our results may provide new insights into the pathogenesis of CIRI, and contribute to the development of treatment strategies for CIRI.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"60 1","pages":"854-861"},"PeriodicalIF":3.9000,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9132463/pdf/","citationCount":"5","resultStr":"{\"title\":\"Curcumin inhibits cerebral ischaemia-reperfusion injury and cell apoptosis in rats through the ERK-CHOP-caspase-11 pathway.\",\"authors\":\"Yue Chen, Lixia Zhang, Zengtai Yang, Jie Yu\",\"doi\":\"10.1080/13880209.2022.2069271\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Context: </strong>Curcumin has a significant effect on cerebral ischaemia-reperfusion injury (CIRI). However, the underlying mechanism is less studied.</p><p><strong>Objective: </strong>This study investigates the role and mechanism of curcumin in CIRI.</p><p><strong>Materials and methods: </strong>CIRI model Sprague-Dawley rats were divided into model, positive control and curcumin low/middle/high dose (50, 100 and 200 mg/kg/d) groups (<i>n</i> = 10 each). Drug intervention was administered by gavage once a day for 4 weeks. We calculated the neurobehavioural score and observed the cerebral infarct volume. Glial cytopathological changes were observed after haematoxylin-eosin staining. Apoptosis was detected by TUNEL (TdT mediated dUTP nick end labelling). Extracellular signal-regulated protein kinase (<i>ERK</i>), C/EBP-homologous protein (<i>CHOP</i>) and <i>caspase-11</i> mRNA were detected by real-time PCR. Phosphorylated ERK (p-ERK), phosphorylated CHOP (p-CHOP) and caspase-11 were detected by Western blot. Superoxide dismutase (SOD) activity was detected by xanthine oxidation method; malondialdehyde (MDA) content by thiobarbituric acid colorimetry; and, glutathione (GSH) by spectrophotometry.</p><p><strong>Results: </strong>Compared with control, the neurobehavioural scores, neuronal apoptosis, MDA, IL-1β, IL-18, mRNAs and protein levels of ERK/p-ERK, CHOP/p-CHOP and caspase-11 in model group were significantly higher (<i>p</i> < 0.01). Compared with model, the positive control and medium/high dose curcumin groups were significantly lower (<i>p</i> < 0.01). However, SOD and GSH decreased significantly in model group but increased significantly in positive control and medium/high dose curcumin groups (<i>p</i> < 0.01). Moreover, curcumin significantly alleviated ischaemic state and neuroinflammation (<i>p</i> < 0.01).</p><p><strong>Discussion and conclusions: </strong>Curcumin may alleviate CIRI through ERK-CHOP-caspase-11 pathway. 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引用次数: 5
摘要
背景:姜黄素对脑缺血再灌注损伤(CIRI)有显著作用。然而，对其潜在机制的研究较少。目的:探讨姜黄素在CIRI中的作用及其机制。材料与方法:将CIRI模型Sprague-Dawley大鼠分为模型组、阳性对照组和姜黄素低、中、高剂量组(50、100、200 mg/kg/d)，每组10只。药物干预方式为灌胃，每天1次，连续4周。计算神经行为学评分，观察脑梗死体积。血红素-伊红染色观察神经胶质细胞病理改变。TUNEL (TdT介导的dUTP缺口末端标记)检测细胞凋亡。实时荧光定量PCR检测细胞外信号调节蛋白激酶(ERK)、C/ ebp同源蛋白(CHOP)和caspase-11 mRNA的表达。Western blot检测磷酸化ERK (p-ERK)、磷酸化CHOP (p-CHOP)和caspase-11。黄嘌呤氧化法检测超氧化物歧化酶(SOD)活性;硫代巴比妥酸比色法测定丙二醛含量;分光光度法测定谷胱甘肽(GSH)。结果:与对照组比较，模型组大鼠神经行为评分、神经元凋亡、MDA、IL-1β、IL-18、mrna及ERK/p-ERK、CHOP/p-CHOP、caspase-11蛋白水平均显著升高(p p p p p)。我们的研究结果可能为CIRI的发病机制提供新的见解，并有助于CIRI治疗策略的发展。
Curcumin inhibits cerebral ischaemia-reperfusion injury and cell apoptosis in rats through the ERK-CHOP-caspase-11 pathway.
Context: Curcumin has a significant effect on cerebral ischaemia-reperfusion injury (CIRI). However, the underlying mechanism is less studied.
Objective: This study investigates the role and mechanism of curcumin in CIRI.
Materials and methods: CIRI model Sprague-Dawley rats were divided into model, positive control and curcumin low/middle/high dose (50, 100 and 200 mg/kg/d) groups (n = 10 each). Drug intervention was administered by gavage once a day for 4 weeks. We calculated the neurobehavioural score and observed the cerebral infarct volume. Glial cytopathological changes were observed after haematoxylin-eosin staining. Apoptosis was detected by TUNEL (TdT mediated dUTP nick end labelling). Extracellular signal-regulated protein kinase (ERK), C/EBP-homologous protein (CHOP) and caspase-11 mRNA were detected by real-time PCR. Phosphorylated ERK (p-ERK), phosphorylated CHOP (p-CHOP) and caspase-11 were detected by Western blot. Superoxide dismutase (SOD) activity was detected by xanthine oxidation method; malondialdehyde (MDA) content by thiobarbituric acid colorimetry; and, glutathione (GSH) by spectrophotometry.
Results: Compared with control, the neurobehavioural scores, neuronal apoptosis, MDA, IL-1β, IL-18, mRNAs and protein levels of ERK/p-ERK, CHOP/p-CHOP and caspase-11 in model group were significantly higher (p < 0.01). Compared with model, the positive control and medium/high dose curcumin groups were significantly lower (p < 0.01). However, SOD and GSH decreased significantly in model group but increased significantly in positive control and medium/high dose curcumin groups (p < 0.01). Moreover, curcumin significantly alleviated ischaemic state and neuroinflammation (p < 0.01).
Discussion and conclusions: Curcumin may alleviate CIRI through ERK-CHOP-caspase-11 pathway. Our results may provide new insights into the pathogenesis of CIRI, and contribute to the development of treatment strategies for CIRI.
期刊介绍：
Pharmaceutical Biology will publish manuscripts describing the discovery, methods for discovery, description, analysis characterization, and production/isolation (including sources and surveys) of biologically-active chemicals or other substances, drugs, pharmaceutical products, or preparations utilized in systems of traditional medicine.
Topics may generally encompass any facet of natural product research related to pharmaceutical biology. Papers dealing with agents or topics related to natural product drugs are also appropriate (e.g., semi-synthetic derivatives). Manuscripts will be published as reviews, perspectives, regular research articles, and short communications. The primary criteria for acceptance and publication are scientific rigor and potential to advance the field.
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