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Article(id=1241720039573868639, tenantId=1146029695717560320, journalId=1205117082300743687, issueId=1241720034091914228, articleNumber=null, orderNo=null, doi=10.14109/j.cnki.xyylc.2024.06.07, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1673884800000, receivedDateStr=2023-01-17, revisedDate=null, revisedDateStr=null, acceptedDate=1706803200000, acceptedDateStr=2024-02-02, onlineDate=1773978727477, onlineDateStr=2026-03-20, pubDate=1719244800000, pubDateStr=2024-06-25, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1773978727477, onlineIssueDateStr=2026-03-20, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1773978727477, creator=13701087609, updateTime=1773978727477, updator=13701087609, issue=Issue{id=1241720034091914228, tenantId=1146029695717560320, journalId=1205117082300743687, year='2024', volume='43', issue='6', pageStart='401', pageEnd='480', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1773978726169, creator=13701087609, updateTime=1773979021315, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1241721272128828343, tenantId=1146029695717560320, journalId=1205117082300743687, issueId=1241720034091914228, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1241721272128828344, tenantId=1146029695717560320, journalId=1205117082300743687, issueId=1241720034091914228, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=432, endPage=436, ext={EN=ArticleExt(id=1241720039871664239, articleId=1241720039573868639, tenantId=1146029695717560320, journalId=1205117082300743687, language=EN, title=Drug for treating CKLD5 deficiency related epileptic seizures: ganaxolone, columnId=1239174991388930543, journalTitle=Chinese Journal of New Drugs and Clinical Remedies, columnName=New Drug Introduction, runingTitle=null, highlight=null, articleAbstract=

Ganaxolone is an oral GABAA receptor positive variant modulator developed by Marinas Pharmaceuticals in the United States, and it can specifically modulate GABAA receptors in the central nervous system to enhance temporal and tonic inhibition for seizure control. In March 2022, the U.S. Food and Drug Administration approved it as the first drug to treat cyclin-dependent kinase-like 5 deficiency based on the results of a major phase Ⅲ clinical trial. Clinical trials have shown that ganaxolone is well tolerated, and the treatment regimen based on this drug is effective in controlling seizure frequency of patients and improving their quality of life.

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加奈索酮（ganaxolone）是美国Marinas制药公司研发的一种口服γ-氨基丁酸A型（GABAA）受体正向变构调节剂，能特异性地调节中枢神经系统中的GABAA受体，加强时相性和紧张性抑制，以控制癫痫发作。2022年3月美国食品和药物管理局基于一项重要的Ⅲ期临床试验结果，批准其作为首个用于治疗细胞周期蛋白依赖性蛋白激酶5缺乏症的药物。临床试验表明，加奈索酮耐受性良好，以该药为基础的治疗方案可有效控制患者癫痫发作频率，提高生活质量。

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黄琳，E-mail：
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李媛媛，女，硕士，主要从事药物个体化治疗的研究，E-mail：

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李媛媛，女，硕士，主要从事药物个体化治疗的研究，E-mail：

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李媛媛，女，硕士，主要从事药物个体化治疗的研究，E-mail：

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Epilepsia, 2017, 58（2）: 181-221., articleTitle=Progress report on new antiepileptic drugs: a summary of the Thirteenth Eilat Conference on New Antiepileptic Drugs and Devices （EILAT ⅩⅢ）, refAbstract=null)], funds=null, companyList=[AuthorCompany(id=1241720040731496599, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241720039573868639, xref=1., ext=[AuthorCompanyExt(id=1241720040739885208, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241720039573868639, companyId=1241720040731496599, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.Department of Pharmacy, People’s Hospital of Peking University, BEIJING 100044, China), AuthorCompanyExt(id=1241720040748273817, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241720039573868639, companyId=1241720040731496599, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.北京大学人民医院 药学部，北京　100044)]), AuthorCompany(id=1241720042241446048, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241720039573868639, xref=2., ext=[AuthorCompanyExt(id=1241720042245640353, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241720039573868639, companyId=1241720042241446048, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2.School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing JIANGSU 211198, China), AuthorCompanyExt(id=1241720042249834658, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241720039573868639, companyId=1241720042241446048, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2.中国药科大学基础医学与临床药学学院，江苏 南京　211198)])], figs=[ArticleFig(id=1241720044443455789, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241720039573868639, language=EN, label=null, caption=null, figureFileSmall=xrN2VKczCKksLbs9tnRr/A==, figureFileBig=coMSNHDX03mO0seUC46OLw==, tableContent=null), ArticleFig(id=1241720044523147571, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241720039573868639, language=CN, label=图1, caption=加奈索酮化学结构式, figureFileSmall=xrN2VKczCKksLbs9tnRr/A==, figureFileBig=coMSNHDX03mO0seUC46OLw==, tableContent=null), ArticleFig(id=1241720044812554556, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241720039573868639, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
临床试验序列号研究阶段适应证干预状态
NCT04285346Ⅱ期结节性硬化症加奈索酮单药尚未招募
NCT03865732Ⅱ期PCDH19基因相关癫痫加奈索酮/安慰剂尚未招募
NCT05249556Ⅲ期细胞周期蛋白依赖性蛋白激酶5缺乏症加奈索酮/安慰剂尚未招募
NCT05323734Ⅲ期结节性硬化症加奈索酮/安慰剂正在招募
NCT04391569Ⅲ期癫痫持续状态，惊厥性癫痫持续状态，非惊厥性癫痫持续状态，癫痫加奈索酮/安慰剂正在招募
NCT03572933Ⅲ期细胞周期蛋白依赖性蛋白激酶5缺乏症加奈索酮/安慰剂尚未招募
), ArticleFig(id=1241720044900634946, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241720039573868639, language=CN, label=表1, caption=

进行中的加奈索酮临床试验

, figureFileSmall=null, figureFileBig=null, tableContent=
临床试验序列号研究阶段适应证干预状态
NCT04285346Ⅱ期结节性硬化症加奈索酮单药尚未招募
NCT03865732Ⅱ期PCDH19基因相关癫痫加奈索酮/安慰剂尚未招募
NCT05249556Ⅲ期细胞周期蛋白依赖性蛋白激酶5缺乏症加奈索酮/安慰剂尚未招募
NCT05323734Ⅲ期结节性硬化症加奈索酮/安慰剂正在招募
NCT04391569Ⅲ期癫痫持续状态，惊厥性癫痫持续状态，非惊厥性癫痫持续状态，癫痫加奈索酮/安慰剂正在招募
NCT03572933Ⅲ期细胞周期蛋白依赖性蛋白激酶5缺乏症加奈索酮/安慰剂尚未招募
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治疗CKLD5缺乏症相关癫痫发作药物：加奈索酮
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李媛媛 1, 2 , 顾群 1 , 黄琳 1
中国新药与临床杂志 | 新药介绍 2024,43(6): 432-436
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中国新药与临床杂志 | 新药介绍 2024, 43(6): 432-436
治疗CKLD5缺乏症相关癫痫发作药物：加奈索酮
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李媛媛1, 2 , 顾群1, 黄琳1
作者信息
  • 1.北京大学人民医院 药学部，北京　100044
  • 2.中国药科大学基础医学与临床药学学院，江苏 南京　211198

    • 李媛媛，女，硕士，主要从事药物个体化治疗的研究，E-mail：

通讯作者:

黄琳，E-mail：
Drug for treating CKLD5 deficiency related epileptic seizures: ganaxolone
Yuan-yuan LI1, 2 , Qun GU1, Lin HUANG1
Affiliations
  • 1.Department of Pharmacy, People’s Hospital of Peking University, BEIJING 100044, China
  • 2.School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing JIANGSU 211198, China
出版时间: 2024-06-25 doi: 10.14109/j.cnki.xyylc.2024.06.07
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摘要
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加奈索酮（ganaxolone）是美国Marinas制药公司研发的一种口服γ-氨基丁酸A型（GABAA）受体正向变构调节剂，能特异性地调节中枢神经系统中的GABAA受体，加强时相性和紧张性抑制，以控制癫痫发作。2022年3月美国食品和药物管理局基于一项重要的Ⅲ期临床试验结果，批准其作为首个用于治疗细胞周期蛋白依赖性蛋白激酶5缺乏症的药物。临床试验表明，加奈索酮耐受性良好，以该药为基础的治疗方案可有效控制患者癫痫发作频率，提高生活质量。

加奈索酮  /  细胞周期蛋白依赖性蛋白激酶5  /  癫痫  /  受体，GABA-A  /  治疗结果  /  安全

Ganaxolone is an oral GABAA receptor positive variant modulator developed by Marinas Pharmaceuticals in the United States, and it can specifically modulate GABAA receptors in the central nervous system to enhance temporal and tonic inhibition for seizure control. In March 2022, the U.S. Food and Drug Administration approved it as the first drug to treat cyclin-dependent kinase-like 5 deficiency based on the results of a major phase Ⅲ clinical trial. Clinical trials have shown that ganaxolone is well tolerated, and the treatment regimen based on this drug is effective in controlling seizure frequency of patients and improving their quality of life.

ganaxolone  /  cyclin-dependent kinase-like 5  /  epilepsy  /  receptors, GABA-A  /  treatment outcome  /  safety
李媛媛, 顾群, 黄琳. 治疗CKLD5缺乏症相关癫痫发作药物：加奈索酮. 中国新药与临床杂志, 2024 , 43 (6) : 432 -436 . DOI: 10.14109/j.cnki.xyylc.2024.06.07
Yuan-yuan LI, Qun GU, Lin HUANG. Drug for treating CKLD5 deficiency related epileptic seizures: ganaxolone[J]. Chinese Journal of New Drugs and Clinical Remedies, 2024 , 43 (6) : 432 -436 . DOI: 10.14109/j.cnki.xyylc.2024.06.07
正文
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细胞周期蛋白依赖性蛋白激酶5（cyclin-dependent kinase-like 5，CDKL5）缺乏症（CDKL5 deficiency disorder，CDD）是一种罕见的X染色体连锁发育性和癫痫性脑病，活产婴儿发病率为1/40 000~1/60 000，男女比例为1∶4[1]。CDKL5基因能产生一种在大脑中高表达的蛋白质，在神经元树突及轴突的形成过程中发挥关键的作用[2]。CDKL5基因突变（新生或嵌合体基因衍生的错义、无义、缺失、插入和剪接位点突变）[2-5]会改变谷氨酸和γ-氨基丁酸A型（γ-aminobuyric acid type-A，GABAA）受体机制，进而破坏兴奋-抑制神经元的平衡引起GABAA能信号的减弱，导致CDD的疾病进展，影响患者神经系统发育[6]。CDD是一种发育性和癫痫性脑病，癫痫是其最常见的初表现，90%以上的患者在出生后3个月内出现癫痫发作，绝大多数抗癫痫药物控制效果不佳，且表现出严重精神运动发育落后，同时具有某些Rett样特征如手功能失用、刻板运动、低眼压、胃肠道症状（如反流、便秘）、睡眠障碍和皮质视觉障碍[7]。目前仍在使用的历史最久的抗癫痫药物苯巴比妥于1912年被开发，并逐渐被应用到新生儿的临床实践中，但由于苯二氮䓬类或苯巴比妥类抗癫痫药物对CDD引起的癫痫发作通常是无效或短暂的（平均有效时间为6个月），且有呼吸抑制和心肌功能损伤等较大不良反应[8]。因此，迫切需要寻找一种有效的治疗方案以减轻CDD患者癫痫发作的频率、持续时间和严重程度。
加奈索酮（ganaxolone，商品名Ztalmy）口服混悬剂是首个获批上市治疗CDD的GABAA受体正向变构调节剂，由美国Marinas制药公司研发，2022年3月18日美国食品和药物管理局（FDA）批准其用于治疗2岁及以上年龄的CDD相关癫痫发作[9]，化学结构式见图1。本文对加奈索酮的药理作用及作用机制、药动学、临床疗效、安全性等进行综述，旨在为临床用药提供参考。
作用机制
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加奈索酮是依照体内的天然抗惊厥神经调节物——神经甾体allopregnanolone合成得到的，属于孕酮类衍生物。与苯二氮䓬类抗癫痫药物劳拉西泮（lorazepam，氯羟去甲安定）和地西泮（diazepam，安定）一样，加奈索酮也是GABAA受体激动剂；但与苯二氮䓬类药物的作用位点不同，加奈索酮抑制其与GABAA氯通道配体t-［35S］丁基二环磷酸盐（半数抑制浓度IC50=80 nmol·L-1）的结合，增强苯二氮䓬类位点配体［3H］氟硝西泮（半数效应浓度EC50=125 nmol·L-1）和GABA位点配体［3H］蝇草酚（EC50=86 nmol·L-1）的结合[8]。由于加奈索酮化学结构中的3β-甲基取代基阻止了其在3α-羟基部分的代谢和氧化，因此它不具有激素活性，也不进行反向转化，能有效地作用于含有δ-亚基的GABAA受体，在加强时相性和紧张性抑制的同时能避免出现其他GABAA受体激动剂如氯巴占（clobazam，氧异安定）产生的相关副作用、快速耐药性等问题[10]。
加奈索酮体内药理实验表明，其可以抑制多种动物模型诱发的癫痫发作，包括戊四唑[11]、最大电休克[12]、荷包牡丹碱[13]、氨茶碱[14]、氟乙酰胺[14]、杏仁核[15]和60 Hz角膜点燃[16]，这表明加奈索酮可以在广泛类型的癫痫发作中发挥治疗作用。
药动学
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加奈索酮的药动学特征是吸收迅速，二相消除，终末半衰期为4 h[17]。给予健康受试者200、400和600 mg的加奈索酮胶囊，在给药后2到3 h内达到峰浓度（cmax），分别为27.9、35.7和41 ng·mL-1。与禁食条件下相比，高脂饮食的受试者服用加奈索酮的cmax和药物-时间曲线下面积（AUC0-12h）分别增加了3倍和2倍。在禁食状态下，cmax与给药剂量成正比[17]。加奈索酮及其代谢物在口服给药后广泛分布到组织中，分配系数约为5。加奈索酮血浆结合率约为99%，终末半衰期为34 h，主要经CYP3A4同工酶代谢，16α-羟基-GNX是其主要代谢产物[19]。加奈索酮55%经粪便排出（其中含有摄入量2%的原型药物），18%经尿液排出（无原型药物）[20]。
未发现加奈索酮的药动学参数在年龄、性别、种族等因素影响下有明显临床差异。肝肾功能损伤对加奈索酮药动学的影响尚未被研究，由于加奈索酮通过肝脏途径代谢，肝功能损伤可能会增加它的血浆浓度[21]。
用法用量
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加奈索酮为口服混悬剂，规格为50 mg·mL-1。患者应根据体重和服药时间逐渐加量至维持剂量：以7日为一个周期，体重在28 kg及以下患者在服药第1个周期单次剂量为6 mg·kg-1，每日3次，此后每个周期单次剂量增加5 mg·kg-1，直至服药3个周期（第22日）后以21 mg·kg-1作为维持剂量至停药前。体重在28 kg以上患者在服药第1个周期单次剂量为150 mg（3 mL），每日3次，每个周期单次剂量增加150 mg（3 mL）直至服药3个周期（第22日）后以600 mg（12 mL）作为维持剂量至停药前。服用加奈索酮前应均匀摇晃1 min，静置1 min后随餐服用。在病情得到控制或因不良反应需停止治疗时，应逐渐减少剂量，避免突然停药，以免增加癫痫发作频率和癫痫持续状态的风险[21]。
临床研究
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Marigold试验（1042-CDD-3001，NCT03572933）是一项多中心、随机、双盲、安慰剂对照的Ⅲ期临床试验，评价了加奈索酮在治疗2岁及以上CDD患者癫痫发作时的有效性和安全性[22]。纳入研究的CDD患者需满足以下条件：（1）具有分子学确认的CDKL5基因突变；（2）具有至少两种抗癫痫药物治疗但未得到控制的早发性癫痫发作史；（3）每28日至少有16次主要运动性癫痫发作［双侧强直（≥3 s持续运动活动）、一般强直-阵挛、双侧阵挛、无张力或局限性至双侧强直-阵挛发作］。本试验共纳入来自8个国家的101例CDD患者，平均年龄7岁（2~21岁），试验包括8周筛选期（确定患者是否符合纳入条件）、6周基线期（确定患者癫痫发作频率），以及17周的双盲期和开放标签扩展期。在双盲期，101例患者随机分为加奈索酮组（n=50）和安慰剂组（n=51），分别给予50 mg·mL-1加奈索酮或安慰剂，起始剂量6 mg·kg-1（体重≤28 kg）或150 mg（体重>28 kg），与食物同服，每日3次，其后逐渐加量，第22日达到21 mg·kg-1（体重≤28 kg）或600 mg（体重>28 kg），每日3次。试验共进行了109周。加奈索酮组及安慰剂组分别有96.0%和92.2%的患者按照方案完成了研究。在整个研究过程中，主要终点指标是接受加奈索酮治疗后的28 d运动性癫痫发作频率中位数的百分比变化。与基线期相比，加奈索酮组28 d运动性癫痫发作频率中位数的百分比变化为-30.7%［四分位距：-49.5%~-1.9%］，安慰剂组为-6.9%（-24.1%~39.7%），达到了试验的主要终点（P=0.003 6）。在开放标签扩展期中，接受加奈索酮治疗至少1年的患者（n=48），运动性癫痫发作频率中位数降低幅度为49.6%。次要终点指标是从基线期到双盲期运动性癫痫发作频率减少至少50%的患者比例，以及在双盲期最后一次就诊时患者家属和医师的临床总体印象量表-总体改善（CGI-I）评分。在双盲期结束时，加奈索酮组24%的患者、安慰剂组10%的患者运动性癫痫发作频率至少减少了50%，组间无显著差异（P=0.064 3），中位数差异为14.7%（95%CI：-4.7~33.8）。在患者家属CGI-I量表中，加奈索酮组63%和安慰剂组44%的患者被评为稍微或明显好转（OR=1.87，95%CI：0.89~3.91）；在医师的CGI-I量表中，加奈索酮组54%和安慰剂组42%的患者被评为稍微或明显好转（OR=1.41，95%CI：0.68~2.94）。
一项探索性、开放标签试验1042-900（NCT02358538）评估了加奈索酮辅助治疗几种罕见遗传性癫痫的安全性和有效性[23]。其中包括7例CDD患者，患者每日3次口服加奈索酮63 mg·kg-1，经过26周的治疗，7例患者28 d运动性癫痫发作频率较基线的中位数百分比变化为-44.4%（-85.3%~99.2%）。其中4例患者进入到研究的开放标签扩展期，并在18个月内癫痫发作频率持续减少，直到研究结束。
1042-CDD-3002（NCT05249556）是一项随机、双盲、安慰剂对照的Ⅲ期临床试验[24]，自2022年4月开始，预计2023年10月结束。该研究将评估年龄6个月到2岁已有标准抗癫痫药物治疗方案的CDD患者在将加奈索酮或安慰剂作为辅助治疗时的疗效、安全性和耐受性；在此期间也将进行药动学评估和群体药动学分析，为个体化用药提供循证依据。由于加奈索酮在多种动物模型中显示了抗癫痫活性，其在结节性硬化症（tuberous sclerosis complex）、PCDH19基因相关癫痫、癫痫持续状态（status epilepticus）等疾病中的抗癫痫作用也在被广泛研究中（表1），有望再获批新的适应证[8]。
安全性
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加奈索酮耐受性良好，多数不良反应为轻度。最常见的不良反应是中枢神经系统的不良反应，如嗜睡、头晕、头痛、抽搐、协调异常[21]。
Marigold试验[22]中服用加奈索酮的43例（86%）患者、服用安慰剂的45例（88%）患者发生了与治疗相关的不良反应。其中发生率≥10%且在加奈索酮组高于安慰剂组的不良反应有嗜睡（36%）、发热（18%）和上呼吸道感染（10%），此外，加奈索酮组中部分患者出现呕吐（10%）、便秘（6%）、唾液分泌过多（6%）、镇静（6%）、季节性过敏（6%）、耳部感染（4%）、皮疹（4%）、尿路感染（2%）。加奈索酮组有6例（12%）患者发生与药物无关的严重不良反应，安慰剂组有5例（10%）。加奈索酮组中2例（4%）、安慰剂组中4例（8%）患者因不良反应（嗜睡、镇静）停止试验。在双盲阶段没有死亡病例。
1042-0600（NCT00465517）是一项为期18周的随机、双盲、安慰剂对照的临床试验，用于评价加奈索酮辅助治疗成人未控制部分性癫痫发作的疗效和安全性[25]。加奈索酮组54例（55.1%）、安慰剂组16例（32.7%）患者发生了与治疗相关的不良反应。加奈索酮组47例（48.0%）、安慰剂组19例（38.8%）患者出现神经系统障碍。加奈索酮组最常见的不良反应为抽搐（5.1%）、协调异常（6.1%）、头晕（16.3%）、头痛（8.2%）、感觉减退（5.1%）、嗜睡（13.3%）、鼻咽炎（5.1%）。加奈索酮组有5例（5.1%）、安慰剂组有4例（8.2%）患者发生与药物无关的严重不良反应。加奈索酮组中7例（7.1%）、安慰剂组中3例（6.1%）患者因不良反应（头痛、嗜睡、抽搐）停止试验。在双盲阶段没有死亡病例。
到目前为止，还没有研究表明加奈索酮会导致细胞突变或致癌，临床前安全药理学研究也没有证据表明其在慢性疾病和人体临床试验相关的剂量下有终末器官毒性。在生殖毒理学研究中，加奈索酮与大鼠或小鼠的胚胎或胎儿畸形无关，也不会显著影响后代的发育[26]。
药物相互作用
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由于加奈索酮主要经过CYP3A4代谢，应避免与可抑制或增强CYP3A4活性的药物（如克拉霉素、伏立康唑、利托那韦、利福平、卡马西平、苯妥英等）联用，必须联用时应注意调整加奈索酮剂量，但不能超过每日最大剂量，并密切关注患者血药浓度[21]。
对于加奈索酮给药量已经稳定，但需要增加酶诱导性抗癫痫药物（如卡马西平、苯妥英、苯巴比妥和扑米酮）作为辅助治疗的患者，加奈索酮的剂量可能需要增加，但是不能超过每日最大剂量。若同时服用加奈索酮和中枢神经系统抑制剂，可能会增加嗜睡和镇静的风险[21]。
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参考文献 引证文献
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2024年第43卷第6期
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doi: 10.14109/j.cnki.xyylc.2024.06.07
  • 接收时间：2023-01-17
  • 首发时间：2026-03-20
  • 出版时间：2024-06-25
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  • 收稿日期：2023-01-17
  • 录用日期：2024-02-02
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    1.北京大学人民医院 药学部，北京　100044
    2.中国药科大学基础医学与临床药学学院，江苏 南京　211198

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2种不同金属材料的力学参数
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species		 占总种数比例
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total species (%)		 属
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species		 占总种数比例
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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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