Article(id=1292135430963618414, tenantId=1146029695717560320, journalId=1246415772164075586, issueId=1292135402790482407, articleNumber=null, orderNo=null, doi=10.13699/j.cnki.1001-6821.2026.11.010, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1773504000000, receivedDateStr=2026-03-15, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1785998693456, onlineDateStr=2026-08-06, pubDate=1781625600000, pubDateStr=2026-06-17, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1785998693456, onlineIssueDateStr=2026-08-06, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1785998693456, creator=13701087609, updateTime=1785998693456, updator=13701087609, issue=Issue{id=1292135402790482407, tenantId=1146029695717560320, journalId=1246415772164075586, year='2026', volume='42', issue='11', pageStart='1501', pageEnd='1650', issueExtLink='null', onlineDate='null', pubDate='1781625600000', pubDateStr='2026-06-17', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=1, specialIssue=null, createTime=1785998686739, creator='13701087609', updateTime=1786014315540, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1292200954833686587, tenantId=1146029695717560320, journalId=1246415772164075586, issueId=1292135402790482407, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1292200954833686588, tenantId=1146029695717560320, journalId=1246415772164075586, issueId=1292135402790482407, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=1560, endPage=1566, ext={EN=ArticleExt(id=1292135431366271599, articleId=1292135430963618414, tenantId=1146029695717560320, journalId=1246415772164075586, language=EN, title=Research of catechin-mediated intestinal HIF2α iron metabolism pathway in plateau polycythemia mice, columnId=1246531407326105792, journalTitle=Chinese Journal of Clinical Pharmacology, columnName=Clinical and Basic Bridging Research, runingTitle=null, highlight=null, articleAbstract=
Objective To explore the mechanism of action of catechin (CAT) on mice with a model of high altitude polycythemia through mediating the intestinal hypoxia-inducible factor-2α (HIF2α) iron metabolism pathway.
Methods SPF-grade male Balb/cmice were randomly divided into control group (reared in a normal atmospheric pressure environment: northeastern Qinghai province, China, at an altitude of 2 260 m, 36°73′ north latitude, 101°75′ east longitude, without any treatment), model group (reared in a high-altitude hypoxic environment: a certain place in southwestern Qinghai province, China, at an altitude of 4 208 m, 32°90′ north latitude, 95°25′ east longitude, without any treatment), the experimental group (based on model group, intragastrically administered with 100 mg·kg-1 CAT once a day from the 29th to the 35th day) and the oe-HIF2α group (based on experimental group, intravenously injected with lentivirus-coated oe-HIF2α plasmids by the tail vein once a day from the 34th to the 35th day). Real-time fluorescence quantitative polymerase chain reaction was used to detect the relative expression level of HIF2α mRNA in intestinal tissues; Western blot assay was used to detect the relative expression levels of HIF2α, B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), cleaved-cysteine-aspartic acid protease 3 (Cleaved-Caspase3), ferroportin (FPN), transferrin receptor (TFRC) in intestinal tissues, as well as the relative expression levels of GATA binding factor 1 (GATA-1) and erythropoietin receptor (EpoR) in bone marrow red blood cells; automatic hematology analyzer was used to detect the levels of hemoglobin, red blood cell count and hematocrit in peripheral blood; the spectrophotometric method was used to detect the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and content of malondialdehyde (MDA) in intestinal tissues; the immunofluorescence staining assay was used to detect the positive expression of ferritin (Ferritin) in intestinal tissues.
Results The relative expression levels of HIF2α mRNA in control group, model group and experimental group were 1.00±0.18, 1.61±0.16 and 1.21±0.13, respectively; the hemoglobin levels in control group, model group, experimental group and oe-HIF2α group were (132.91±11.44), (221.37±26.92), (178.65±19.32) and (206.33±21.37) g·L-1, respectively; the red blood cell count levels were (4.79±0.75), (9.26±1.11), (6.08±1.03) and (7.74±0.96)×1012·L-1, respectively; the hematocrit levels were (44.17±4.06)%, (63.58±6.38)%, (51.79±4.45)% and (58.24±5.07)%, respectively; the relative expression levels of GATA-1 protein were 1.00±0.17, 2.03±0.33, 1.52±0.19 and 1.80±0.23, respectively; the relative expression levels of EpoR were 1.00±0.11, 1.83±0.31, 1.29±0.20 and 1.62±0.24, respectively; the relative fluorescence intensities of Ferritin were 1.00±0.12, 7.86±0.97, 2.97±0.49 and 4.75±0.51, respectively; the relative expression levels of FPN protein were 1.00±0.14, 1.69±0.25, 1.31±0.18 and 1.52±0.19, respectively; the relative expression levels of TFRC protein were 1.00±0.10, 2.18±0.23, 1.67±0.15 and 1.86±0.15, respectively. There were statistically significant differences in the above-mentioned indicators between model group and control group, between experimental group and model group, and between oe-HIF2α group and experimental group (all P<0.05).
Conclusion CAT can inhibit cell apoptosis, oxidative stress and excessive iron metabolism in the intestines of mice with high altitude polycythemia by mediating the expression of intestinal HIF2α, and play a role in the prevention and treatment of high altitude polycythemia.
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目的 探究儿茶素（CAT）通过介导肠道缺氧诱导因子-2α（HIF2α）铁代谢途径对高原红细胞增多症模型小鼠的作用机制。
方法 SPF级Balb/c雄性小鼠随机分为对照组（饲养于正常大气压环境：中国青海省东北部，海拔2 260 m，北纬36°73′，东经101°75′，不做任何处理）、模型组（饲养于高原低氧环境：中国青海省西南部某地，海拔4 208 m，北纬32°90′，东经95°25′，不做任何处理）、实验组（基于模型组，于第29至第35 d每天1次灌胃100 mg·kg-1 CAT）和oe-HIF2α组（基于实验组，于第34至35 d，每天尾静脉注射慢病毒包被的oe-HIF2α质粒）。用实时荧光定量聚合酶链式反应检测肠组织HIF2α mRNA相对表达水平；用蛋白质印迹法检测肠组织中HIF2α、B细胞淋巴瘤-2（Bcl-2）、Bcl-2相关X蛋白（Bax）、剪切型半胱氨酸-天冬氨酸蛋白酶3（Cleaved-Caspase3）、铁转运蛋白（FPN）、转铁蛋白受体（TFRC）、骨髓红细胞中GATA结合因子1（GATA-1）和促红细胞生成素受体（EpoR）蛋白相对表达水平；用全自动血液分析仪检测外周血中血红蛋白、红细胞计数和红细胞压积水平；用分光光度法检测肠组织超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）的活力及丙二醛（MDA）含量；用免疫荧光染色实验检测肠组织中铁蛋白（Ferritin）的阳性表达。
结果 对照组、模型组和实验组的HIF2α mRNA相对表达水平分别为1.00±0.18、1.61±0.16和1.21±0.13；对照组、模型组、实验组和oe-HIF2α组的血红蛋白水平分别为（132.91±11.44）、（221.37±26.92）、（178.65±19.32）和（206.33±21.37）g·L-1，红细胞计数水平分别为（4.79±0.75）、（9.26±1.11）、（6.08±1.03）和（7.74±0.96）×1012·L-1，红细胞压积水平分别为（44.17±4.06）%、（63.58±6.38）%、（51.79±4.45）%和（58.24±5.07）%，GATA-1蛋白相对表达水平分别为1.00±0.17、2.03±0.33、1.52±0.19和1.80±0.23，EpoR相对表达水平分别为1.00±0.11、1.83±0.31、1.29±0.20和1.62±0.24，Ferritin相对荧光强度分别为1.00±0.12、7.86±0.97、2.97±0.49和4.75±0.51，FPN蛋白相对表达水平分别为1.00±0.14、1.69±0.25、1.31±0.18和1.52±0.19，TFRC蛋白相对表达水平分别为1.00±0.10、2.18±0.23、1.67±0.15和1.86±0.15。模型组上述指标与对照组相比，实验组与模型组相比，oe-HIF2α组与实验组相比，在统计学上差异均有统计学意义（均P<0.05）。
结论 CAT可以通过介导肠道HIF2α表达，抑制高原红细胞增多症小鼠肠道中细胞凋亡、氧化应激和铁代谢亢进，对高原红细胞增多症发挥防治作用。
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刘芳（1972-），女，博士，教授，主要从事高原红细胞增多症的发病机制相关研究
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