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Article(id=1241768181262516675, tenantId=1146029695717560320, journalId=1205117082300743687, issueId=1241768176522957402, articleNumber=null, orderNo=null, doi=10.14109/j.cnki.xyylc.2024.05.03, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1680710400000, receivedDateStr=2023-04-06, revisedDate=null, revisedDateStr=null, acceptedDate=1709481600000, acceptedDateStr=2024-03-04, onlineDate=1773990205350, onlineDateStr=2026-03-20, pubDate=1716566400000, pubDateStr=2024-05-25, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1773990205350, onlineIssueDateStr=2026-03-20, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1773990205350, creator=13701087609, updateTime=1773990205350, updator=13701087609, issue=Issue{id=1241768176522957402, tenantId=1146029695717560320, journalId=1205117082300743687, year='2024', volume='43', issue='5', pageStart='321', pageEnd='400', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1773990204220, creator=13701087609, updateTime=1773992176593, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1241776449330414547, tenantId=1146029695717560320, journalId=1205117082300743687, issueId=1241768176522957402, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1241776449330414548, tenantId=1146029695717560320, journalId=1205117082300743687, issueId=1241768176522957402, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=333, endPage=338, ext={EN=ArticleExt(id=1241768181627421125, articleId=1241768181262516675, tenantId=1146029695717560320, journalId=1205117082300743687, language=EN, title=Novel animal and non-animal cardiac safety evaluation models, columnId=1207314219599499390, journalTitle=Chinese Journal of New Drugs and Clinical Remedies, columnName=Review, runingTitle=null, highlight=null, articleAbstract=

Drug-induced cardiotoxicity is one of the important reasons for the failure of drug development, and it is urgent to establish methods to screen the impact of drugs on the heart in the early stage. However, the traditional drug safety evaluation models are unable to meet the requirements of drug development. Therefore, the development of efficient and inexpensive drug safety evaluation and mechanism study models are very important for the development of new drugs and rational clinical application of drugs. In recent years, in addition to traditional animal models, the zebrafish, Drosophila,and Caenorhabditis elegans have been used for drug safety research. Based on transgenic technology, humanized animal models with gene expression profiles and regulation similar to that of humans can be established, and the development and application of such models can be used to solve the problem of species differences in drug research. In addition, non-animal methods such as organ chips, organoids, and network toxicology have also been developed. The novel cardiac safety evaluation models would be helpful for drug cardiotoxicity prevention and treatment, as well as drug development.

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药物诱导的心脏毒性是药物研发失败的重要原因之一，亟需建立方法早期筛查新药对心脏的影响。但是，传统药物心脏安全性评价模型已不能满足药物研发的需求。因此，开发高效、廉价的药物心脏安全性的评价和机制研究模型对新药研发和药物的临床合理应用至关重要。近年来，除传统动物模型外，斑马鱼、果蝇、秀丽隐杆线虫等也被用于药物毒性研究。基于转基因技术可以建立基因表达谱和调节方式与人类相似的人源化动物模型，这类模型的开发和应用有助于解决药物研究中的种属差异问题。此外，器官芯片、类器官、网络毒理学等非动物方法也相继被开发。新型药物心脏安全性评价模型有助于药物心脏毒性防治及药物开发。

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蒋雅楠
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温正超，男，硕士在读，主要从事药理学的研究，E-mail: 。

蒋雅楠，女，研究员，博士生导师，博士，主要从事肿瘤心脏病学研究和肿瘤相关生物信息学的研究，E-mail:

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物种名拉丁名/英文名单价/元心率/次·min-1表达hERG通道与人类基因相似性
小鼠Mus musculus20~40200~600否95%
大鼠Rattus norvegicus60~80370~580否90%
豚鼠Cavia porcellus150~300200~360是-
家兔Oryctolagus cuniculus90~100180~250是-
比格犬Beagle1 000~2 000130~150是95%
家猪Sus scrofa domesticu2 000~3 000100~110是97%
山羊Capra hircus4 000~5 00070~80是95%
食蟹猴Macaca fascicularis100 000~200 000188~238是94%
), ArticleFig(id=1241768187306508926, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241768181262516675, language=CN, label=表1, caption=

心脏安全性评价哺乳动物模型

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物种名拉丁名/英文名单价/元心率/次·min-1表达hERG通道与人类基因相似性
小鼠Mus musculus20~40200~600否95%
大鼠Rattus norvegicus60~80370~580否90%
豚鼠Cavia porcellus150~300200~360是-
家兔Oryctolagus cuniculus90~100180~250是-
比格犬Beagle1 000~2 000130~150是95%
家猪Sus scrofa domesticu2 000~3 000100~110是97%
山羊Capra hircus4 000~5 00070~80是95%
食蟹猴Macaca fascicularis100 000~200 000188~238是94%
), ArticleFig(id=1241768187423949441, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241768181262516675, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
名称种属原代/
传代		来源部位传代
原代大鼠乳鼠成纤维细胞［29］大鼠原代成纤维细胞是
原代大鼠乳鼠心肌细胞［30］大鼠原代心室肌细胞否
原代大鼠成鼠心肌细胞［31］大鼠原代心室肌细胞否
原代小鼠乳鼠心肌细胞［32］小鼠原代心室肌细胞否
原代小鼠乳鼠成纤维细胞［33］小鼠原代成纤维细胞是
HL-1［34］小鼠传代心房肌细胞是
AC16［35］人传代心肌细胞是
H9c2［36］大鼠传代心肌细胞是
), ArticleFig(id=1241768187541389958, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241768181262516675, language=CN, label=表2, caption=

心脏毒性检测细胞模型

, figureFileSmall=null, figureFileBig=null, tableContent=
名称种属原代/
传代		来源部位传代
原代大鼠乳鼠成纤维细胞［29］大鼠原代成纤维细胞是
原代大鼠乳鼠心肌细胞［30］大鼠原代心室肌细胞否
原代大鼠成鼠心肌细胞［31］大鼠原代心室肌细胞否
原代小鼠乳鼠心肌细胞［32］小鼠原代心室肌细胞否
原代小鼠乳鼠成纤维细胞［33］小鼠原代成纤维细胞是
HL-1［34］小鼠传代心房肌细胞是
AC16［35］人传代心肌细胞是
H9c2［36］大鼠传代心肌细胞是
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新型动物和非动物药物心脏安全性评价模型
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温正超 1 , 张可娇 1 , 许金城 1 , 蒋雅楠 1, 2
中国新药与临床杂志 | 综述 2024,43(5): 333-338
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中国新药与临床杂志 | 综述 2024, 43(5): 333-338
新型动物和非动物药物心脏安全性评价模型
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温正超1 , 张可娇1, 许金城1, 蒋雅楠1, 2
作者信息
  • 1.哈尔滨医科大学药学院　药理学教研室，黑龙江　哈尔滨　150081
  • 2.黑龙江省医学科学院北方转化医学研究合作中心，黑龙江　哈尔滨　150086

    • 温正超，男，硕士在读，主要从事药理学的研究，E-mail: 。

    蒋雅楠，女，研究员，博士生导师，博士，主要从事肿瘤心脏病学研究和肿瘤相关生物信息学的研究，E-mail:

通讯作者:

蒋雅楠
Novel animal and non-animal cardiac safety evaluation models
Zheng-chao WEN1 , Ke-jiao ZHANG1, Jin-cheng XU1, Ya-nan JIANG1, 2
Affiliations
  • 1.Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin HEILONGJIANG 150081, China
  • 2.Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences,Harbin HEILONGJIANG 150086, China
出版时间: 2024-05-25 doi: 10.14109/j.cnki.xyylc.2024.05.03
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摘要
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药物诱导的心脏毒性是药物研发失败的重要原因之一，亟需建立方法早期筛查新药对心脏的影响。但是，传统药物心脏安全性评价模型已不能满足药物研发的需求。因此，开发高效、廉价的药物心脏安全性的评价和机制研究模型对新药研发和药物的临床合理应用至关重要。近年来，除传统动物模型外，斑马鱼、果蝇、秀丽隐杆线虫等也被用于药物毒性研究。基于转基因技术可以建立基因表达谱和调节方式与人类相似的人源化动物模型，这类模型的开发和应用有助于解决药物研究中的种属差异问题。此外，器官芯片、类器官、网络毒理学等非动物方法也相继被开发。新型药物心脏安全性评价模型有助于药物心脏毒性防治及药物开发。

心脏毒性  /  药物评价，临床前  /  模型，动物  /  类器官

Drug-induced cardiotoxicity is one of the important reasons for the failure of drug development, and it is urgent to establish methods to screen the impact of drugs on the heart in the early stage. However, the traditional drug safety evaluation models are unable to meet the requirements of drug development. Therefore, the development of efficient and inexpensive drug safety evaluation and mechanism study models are very important for the development of new drugs and rational clinical application of drugs. In recent years, in addition to traditional animal models, the zebrafish, Drosophila,and Caenorhabditis elegans have been used for drug safety research. Based on transgenic technology, humanized animal models with gene expression profiles and regulation similar to that of humans can be established, and the development and application of such models can be used to solve the problem of species differences in drug research. In addition, non-animal methods such as organ chips, organoids, and network toxicology have also been developed. The novel cardiac safety evaluation models would be helpful for drug cardiotoxicity prevention and treatment, as well as drug development.

cardiotoxicity  /  drug evaluation, preclinical  /  models, animal  /  organoids
温正超, 张可娇, 许金城, 蒋雅楠. 新型动物和非动物药物心脏安全性评价模型. 中国新药与临床杂志, 2024 , 43 (5) : 333 -338 . DOI: 10.14109/j.cnki.xyylc.2024.05.03
Zheng-chao WEN, Ke-jiao ZHANG, Jin-cheng XU, Ya-nan JIANG. Novel animal and non-animal cardiac safety evaluation models[J]. Chinese Journal of New Drugs and Clinical Remedies, 2024 , 43 (5) : 333 -338 . DOI: 10.14109/j.cnki.xyylc.2024.05.03
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随着医药产业的迅速发展，新药研发投入不断增加。然而，大量药物由于心血管不良反应而退出临床试验或严格限制临床使用，尤其是抗肿瘤药和心血管疾病治疗药物［1,2］。心脏毒性是制药行业面临的主要挑战，迫切需要在药物研发早期筛查新药对心脏的影响。除大鼠、小鼠等常用动物模型外，斑马鱼、果蝇、秀丽隐杆线虫等也被用于药物毒性研究。基于转基因技术可以建立基因表达谱和调节方式与人类相似的人源化动物模型，这类模型的开发和应用有助于解决药物研究中的种属差异问题。近年来，类器官、心脏芯片、网络毒理学等逐渐被开发用于药物心脏安全性检测，不仅可实现准确检测，而且可减少药物研发过程中的动物使用。本文综述新型药物心脏安全性评价模型，以期为药物心脏毒性研究和促进新药开发提供参考。
心脏安全性评价动物模型
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1　传统动物模型
传统动物模型是重要的心脏安全性评价模型，主要包括小鼠、大鼠、豚鼠、兔、犬、猪、羊、猴等，见表1。涉及动物实验均需符合“3R”原则——减少（reduction）、替代（replacement）和优化（refinement）。这类模型可以从整体水平直接体现药物的心脏毒性。以小鼠和大鼠为代表的啮齿类动物模型作为最常用的动物模型具有成本低，繁殖迅速，更容易进行基因编辑、建立转基因动物模型等优点，ZHAO等［3］通过大鼠与小鼠模型，发现多柔比星所诱导的心脏毒性新靶点，但啮齿类动物电生理功能与人仍存在一定差异。猪、犬、羊等大型哺乳动物心脏电生理与人类相似，但是饲养维护成本较高。
2　非哺乳类动物模型
除了传统的哺乳动物可作为药物心脏安全性的评价模型，近年来，越来越多的非哺乳类动物也成为评价药物心脏安全性的新模型，如斑马鱼、果蝇、秀丽隐杆线虫等。与哺乳动物模型相比，新模型具有价格便宜、生命周期短和繁育能力强等优点。
2.1　斑马鱼模型
斑马鱼属鲤科，又名蓝条鱼、花条鱼，体长约4厘米，体呈纺锤形，稍侧扁。斑马鱼模型更符合动物实验“3R”原则且具有许多优势：一方面其繁殖力强且不受季节影响、发育快体积小、易于饲养、价格便宜，适用于药物半数致死量的评估；另一方面斑马鱼的解剖结构、生理过程和对药物的毒性反应与人近似，胚胎和幼体呈透明状便于观察，因此可以快速筛选致心脏毒性的药物［4］。ZHU等［5,6］通过观察斑马鱼的心律、心率、心包水肿、循环、出血和血栓形成这6个特异性表型评估心脏毒性，评估了7种已知心血管毒性药物（阿司匹林、氯米帕明、环磷酰胺、尼莫地平、奎宁、特非那定和维拉帕米）和2种非心血管毒性药物（庆大霉素和四环素）的作用。所有检测的心脏毒性药物均可引起斑马鱼心包水肿和循环障碍，而非心脏毒性药物未对斑马鱼产生明显的心血管毒性。斑马鱼对心脏毒性药物和非心脏毒性药物的反应与人类相似，总体预测成功率为100%。SUN等［7］在斑马鱼模型上验证多柔比星可诱发心脏毒性，并基于该模型发现褪黑素可削弱多柔比星的心脏毒性。这些研究提示，斑马鱼是一种可用于快速筛查药物心脏毒性的动物模型。
2.2　果蝇模型
果蝇属于无脊椎动物，其心脏和大动脉合并称为背血管，由中胚层细胞发育而来，负责输送血液。虽然果蝇心脏结构比脊椎动物简单得多，但其背血管与脊椎动物的心脏发育过程及功能相似，使果蝇作为心脏毒性评价模型动物成为可能。果蝇易于饲养、生命周期短、繁殖能力强（每次可产2 000个卵）、维护成本低、基因和细胞通路高度保守。据统计，77%的人类疾病基因具有果蝇对应基因，其中26个被确定与心血管疾病有关［8］。果蝇模型已经帮助识别了心律失常［9］和心房颤动［10］的关键基因或通路。同时也被应用于限制型心肌病［11,12］、扩张型心肌病［13, 14］、肥厚型心肌病［15, 16］及心脏衰老［17］的研究。ZABIHI-HESARI等［18］通过果蝇模型发现重金属锌（Zn）或镉（Cd）的心脏毒性，并证实金属响应转录因子-1对重金属心脏毒性的保护作用。以上结果提示，果蝇有望成为重要的药物心脏安全性评价模型。
2.3　秀丽隐杆线虫模型
秀丽隐杆线虫是一种食细菌的线性动物，其成体仅1.5 mm长，雌雄同体，繁殖速度快，生命周期短（约23 d）。秀丽隐杆线虫的基因组与RNA信息库完整，为筛选工作提供了极大的便利［19］。而且秀丽隐杆线虫的咽泵与人类心脏具有高度的同源性［20］，其咽泵速率可作为评价心脏功能的替代指标［21］。RUSSO等［22］利用线虫模型证明Cu2+可加重免疫球蛋白轻链的心脏毒性作用。秀丽隐杆线虫模型有望成为评价药物心脏毒性安全性的初筛模型。
3　人源化动物模型
动物模型可从整体水平直观地反映药物的毒性作用，但仍与人类存在物种差异的问题。以小鼠为代表的动物尽管与人类的基因组具有高度同源性，但仍有一些关键功能性基因在人鼠上不完全保守，导致基因功能存在差异，而人源化动物的应用有助于解决这一问题。人源化动物模型是指携带有人源的基因、细胞、组织和器官的动物模型，其具有与人类更为接近的生理病理特征。人源化动物模型能在一定程度上克服基因差异造成的种属差异，进而从动物实验上反映药物在人体中的作用。抵抗素（resistin）在人类和小鼠体内的作用不同，人抵抗素介导炎症反应诱导心脏功能障碍［23］，而小鼠抵抗素可诱发胰岛素抵抗［24］。SCHWARTZ等［25］建立了稳定表达人抵抗素基因的人源化小鼠模型（Hum Retn小鼠），应用该模型发现升高的抵抗素可作为蒽环类药物所致心脏毒性的生物标志物。
然而，人源化动物在应用上也有其局限性，一是人源化动物的基础是免疫缺陷动物，而免疫缺陷动物饲养要求较高，空气洁净度必须达到万级以上，甚至在有些地区达到百级方能满足其饲养要求；二是目前人源化动物相对于传统实验动物购买成本较高；三是由于知识产权的原因，部分人源化动物在国内还无法采购；四是国内开发的具有独立知识产权的人源化动物生物学特性仍存在一定问题，从而影响了人源化动物的应用。
心脏安全性评价细胞模型
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1　传统细胞水平模型
离体细胞模型与动物模型相比具有快速、敏感、特异性高、条件易控等优点，可以用于药物初步筛选［26］。传统心脏安全性研究的细胞模型主要包括哺乳动物原代心肌细胞、原代成纤维细胞、异源表达人基因的哺乳动物细胞等模型，见表2。与传代细胞相比，原代细胞的价格和培养难度更高，但结构和功能上更接近在体细胞。除常规药物心脏毒性研究以外，心房肌细胞更适用于药物诱发的心房颤动研究［27, 28］，成纤维细胞适用于纤维化研究［29］。
2　人多能干细胞诱导的心肌细胞（hiPSC-CM）模型
hiPSC-CM具有众多优点：一是不使用胚胎或卵细胞，没有伦理学问题；二是由体细胞制备的专有干细胞，因此也不会有免疫排斥的问题；三是hiPSC-CM可表达肌丝蛋白，并具有与原代心肌细胞相类似的电生理特性，可以表达多个与人心肌动作电位相关的离子通道，如人类Ether-à-go-go相关基因（hERG）通道［37］。DOHERTY等［38］用24种临床上无心血管不良反应的药物（阿司匹林、阿莫西林等）和18种具有心血管不良反应的药物（硝苯地平、异丙肾上腺素等）作用于体外培养的hiPSC-CM，并检测hiPSC-CM的细胞活力、活性氧、肌钙蛋白、脂质及心率等指标，发现24种心脏安全药物均未对hiPSC-CM产生不良影响，而18种心脏风险药中的16种都表现出心脏毒性指标改变。这些研究为hiPSC-CM作为药物心脏毒性的评价模型提供了依据。
3　稳定转染hERG基因的HEK293细胞
hERG通道是药物安全筛查的重要指标之一，与多种药物所引起的长QT间期综合征（long QT syndrome，LQTS）有关，如抗肿瘤药三氧化二砷［39］、COVID-19治疗药物氯喹和羟基氯喹［40, 41］、抗组胺药特非那定等均可通过阻滞hERG通道诱发LQTS［42, 43］。HEK293细胞衍生自人胚胎肾细胞的细胞系，具有高转染率的特点，常作为工具细胞研究基因表达调控。ZHAN等［44］通过稳定转染hERG基因的HEK293细胞模型评价芦丁卡平的心脏毒性和对hERG通道的影响及其作用机制。ZHAO等［45］同样利用该模型，发现三氧化二砷通过干扰hERG通道向细胞膜的传输进而造成心肌损伤。
新型非动物心脏安全性评价模型
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2022年8月，美国食品和药物管理局（FDA）批准了全球首个完全基于“类器官芯片”研究获得临床前数据的新药进入临床试验（NCT04658472）［46］。2023年1月，期刊 《Science》发文，FDA不再要求在药物临床试验前进行动物实验［47］，诸多证据表明非动物模型逐渐成为临床试验不可或缺的一部分。非动物模型不仅避免了动物与人类之间存在的较大差异，而且可以更好地控制实验条件，有助于准确评估药物的效果。因此，一些非动物心脏安全性评价模型如类器官、心脏芯片、网络毒理学等技术逐渐用于药物安全性评价。
1　心脏类器官
类器官是一种能在体外培养的具有三维结构的微器官，由多功能干细胞、维持和诱导分化的相关因子及基质胶等培育而成，拥有与真实器官类似的复杂结构，能够模拟真实器官的生理功能［48］。与动物模型相比，类器官最大优势在于克服了种属差异。RICHARDS等［49］培育hiPSC-CM，在注入营养梯度扩散的3D模型中建立了心脏类器官，而后对其进行局部冷冻、持续肾上腺素刺激及缺氧等处理以模拟慢性心肌梗死状态。结果显示，应用类器官模型鉴定出的心肌梗死相关基因与在多个物种鉴定出的基因高度重叠。同时，应用该模型证实多柔比星可加重心肌梗死诱导的心肌损伤。该研究提示，心脏类器官可用于筛选药物的心脏毒性。然而，目前心脏类器官模型仍存在限制因素，一方面因为心脏相较于其他器官结构更为复杂，制作的类器官模型不能完全模拟心脏的功能；另一方面因为类器官在体外培养，其所处培养液与真实心脏所处微环境仍有较大差距。
2　心脏芯片
心脏芯片技术是在微米大小的流体腔室中，利用微流控技术控制流体流动，在连续灌注的条件下培养细胞。通过模拟心肌细胞所处的微环境基质以及生物化学特性，进而研究细胞之间的相互作用。不同于心脏类器官的整体性，心脏芯片目的在于构建心脏功能的最小单位，通过光学测量法（钙成像、荧光）或电测量法（电化学免疫传感器、裂纹传感器），观察细胞的生长与分化进而监测药物的心脏毒性［50］。癌症患者在进行化疗时，药物的心脏毒性在早期不易发现。LEE等［51］构建心脏芯片模型，使用电化学免疫传感器技术监测到多柔比星诱导心肌组织纤维化的过程。SHIN等［52］应用心脏芯片模型，通过检测肌酸激酶同工酶的变化，进而评估多柔比星的心脏毒性。心脏芯片的高准确性与高灵敏性，为未来癌症患者化疗诱导的心脏毒性提供了一个早期检测与预测的方法［51］。心脏芯片的缺点在于技术壁垒高、市场商业化低、无法大规模生产与应用。
3　网络毒理学评价
网络毒理学评价是指运用机器学习方法建立识别心脏毒性化合物的分类模型。先是从药物不良反应数据库中搜集具有心脏毒性的化合物，之后运用软件计算和筛选，通过算法构建定量构效关系（quantitative structure-activity relationship，QSAR）模型，并在此基础上交叉验证及优化，从而构建预测药物的心脏毒性的模型［53］。HASINOFF等［54］通过构建QSAR模型，评估了多柔比星的心脏毒性，并发现二氧哌嗪类似物右丙亚胺可通过抑制拓扑异构酶Ⅱ，缓解多柔比星的心脏毒性。网络毒理学建立了一类基于化合物结构的新型药物毒性预测模型。
展望
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在药物研发过程中，心脏毒性是导致药物研发失败的主要原因之一，因此药物的心脏安全性评价至关重要。在实际应用中可综合性应用多个筛选模型，取长补短。例如在药物研发初期，可先通过网络毒理学进行初步筛选，而后再于细胞水平、组织水平、整体动物水平模型进行验证。同时，也可根据需要选择心脏类器官、心脏芯片和人源化动物等新型模型。希望在不远的未来，能建立一种更全面、准确、高效、价廉的药物心脏安全性评价体系。
基金
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  • 国家自然科学基金(82370269)
  • 黑龙江省自然科学基金(LH2021H018)
  • 黑龙江省博士后科学基金(LBH-Q21134)
文献
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2024年第43卷第5期
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文章信息
doi: 10.14109/j.cnki.xyylc.2024.05.03
  • 接收时间：2023-04-06
  • 首发时间：2026-03-20
  • 出版时间：2024-05-25
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出版历史
  • 收稿日期：2023-04-06
  • 录用日期：2024-03-04
基金
国家自然科学基金(82370269)
黑龙江省自然科学基金(LH2021H018)
黑龙江省博士后科学基金(LBH-Q21134)
作者信息
    1.哈尔滨医科大学药学院　药理学教研室，黑龙江　哈尔滨　150081
    2.黑龙江省医学科学院北方转化医学研究合作中心，黑龙江　哈尔滨　150086

通讯作者:

蒋雅楠
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https://castjournals.cast.org.cn/joweb/zgxyylczz/CN/10.14109/j.cnki.xyylc.2024.05.03
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2种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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