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Brain Behav Immun:振奋人心!老药新用,抗炎药可有效对抗脑卒中,促进脑细胞再生

2016-11-29 MedSci MedSci原创

全球内脑卒中是导致死亡和残疾的第二大原因,卒中后会阻断大脑中的血液流动破坏脑细胞。现在,来自英国曼彻斯特大学的一项新的研究表明,一种已经批准用于治疗其他疾病的药物不仅可限制卒中的危害还可促进脑细胞的修复。在大鼠中,研究人员已证实该药物可减少脑细胞的死亡数量,并刺激新的脑细胞的产生,该研究结果已发表于Brain, Behavior, and Immunity。该研究探究了缺血性脑卒中,当机体发生缺血

卒中是世界上导致死亡和残疾的第二大原因,卒中后会阻断大脑中的血液流动破坏脑细胞。现在,来自英国曼彻斯特大学的一项新的研究表明,一种已经批准用于治疗其他疾病的药物不仅可限制卒中的危害还可促进脑细胞的修复。

在大鼠中,研究人员已证实该药物可减少脑细胞的死亡数量,并刺激新的脑细胞的产生,该研究结果已发表于Brain Behavior and Immunity。

该研究探究了缺血性脑卒中,当机体发生缺血性脑卒中时,可阻断给大脑供应氧气的动脉血。

研究人员在脑卒中小鼠中使用了一种抗炎药——IL-1受体拮抗剂(IL-1Ra)。结果发现,IL-1Ra不仅可在卒中早期阶段减少脑损伤,还可在大鼠卒中后几天内促进新的脑细胞(神经元)数量的增加。而且这一效果与小鼠的年龄及胖瘦无关。

研究人员指出,虽然卒中本身也可以引发机体损伤后的一个强大的修复反应,但是许多新产生的细胞并不能整合至原有的脑神经系统中。

当研究人员分析IL-1Ra对大鼠大脑神经元再生的影响时,他们发现,该药不仅可促进干细胞的增殖,还能显著提高脑缺血后神经细胞的迁移,并显著增加新生神经元的数目。

既往研究因无法处理脑卒中中所发生的炎症反应,因此无法将其实验室发发现的药物成功应用与临床,现在这个实验结果为IL-1Ra的使用提供了强有力的支撑,不过未来仍需进一步的大规模临床试验研究以探究该药在人体内的效果。

原始出处:

[1] Catharine Paddock PhD.Stroke: New drug limits brain damage and promotes repair.  MNT.28 November 2016.


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    2016-12-01 wxl882001

    好资料,值得学习

    0

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    2016-12-01 xiaotaiyang1

    了解一下

    0

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  5. [GetPortalCommentsPageByObjectIdResponse(id=1947842, encodeId=103e194e8429a, content=<a href='/topic/show?id=e54d8483db' target=_blank style='color:#2F92EE;'>#HAV#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=95, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8483, encryptionId=e54d8483db, topicName=HAV)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3fc52500170, createdName=12498cbcm00(暂无昵称), createdTime=Fri Mar 17 05:27:00 CST 2017, time=2017-03-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=159469, encodeId=65c51594692e, content=好资料,值得学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=124, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6KcicAVC1MwuOgo3iaicb1Imgk1yIfnvr6oXzibcAFB6puAyNJXbzWhNuLqaFYBVRWjh7rghkvFLPxMAfD5ib3nXwVD/0, createdBy=bed21972958, createdName=wxl882001, createdTime=Thu Dec 01 17:39:28 CST 2016, time=2016-12-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=159374, encodeId=fc721593e4df, content=了解一下, beContent=null, objectType=article, channel=null, level=null, likeNumber=146, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=90f31612316, createdName=xiaotaiyang1, createdTime=Thu Dec 01 11:00:52 CST 2016, time=2016-12-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1346734, encodeId=895b1346e3405, content=<a href='/topic/show?id=f20155404fc' target=_blank style='color:#2F92EE;'>#抗炎药#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=92, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55404, encryptionId=f20155404fc, topicName=抗炎药)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f49517, createdName=xinmeili, createdTime=Thu Dec 01 05:27:00 CST 2016, time=2016-12-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1424896, encodeId=2fc914248962a, content=<a href='/topic/show?id=bbd084993fd' target=_blank style='color:#2F92EE;'>#脑细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=99, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84993, encryptionId=bbd084993fd, topicName=脑细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=39a23929286, createdName=bettycmoon, createdTime=Thu Dec 01 05:27:00 CST 2016, time=2016-12-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1521862, encodeId=0695152186243, content=<a href='/topic/show?id=f83866137f' target=_blank style='color:#2F92EE;'>#EHA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6613, encryptionId=f83866137f, topicName=EHA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=937d11405368, createdName=qjddjq, createdTime=Thu Dec 01 05:27:00 CST 2016, time=2016-12-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=159007, encodeId=7dba15900edc, content=看到了希望,棒棒的, beContent=null, objectType=article, channel=null, level=null, likeNumber=123, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=7a3e1928208, createdName=顾小北大魔王, createdTime=Wed Nov 30 00:06:58 CST 2016, time=2016-11-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=158973, encodeId=cd661589e3cc, content=可以更加适合运用到临床, beContent=null, objectType=article, channel=null, level=null, likeNumber=103, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7b4c1651704, createdName=1ddcba5em94(暂无匿称), createdTime=Tue Nov 29 21:47:16 CST 2016, time=2016-11-29, status=1, ipAttribution=)]
  6. [GetPortalCommentsPageByObjectIdResponse(id=1947842, encodeId=103e194e8429a, content=<a href='/topic/show?id=e54d8483db' target=_blank style='color:#2F92EE;'>#HAV#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=95, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8483, encryptionId=e54d8483db, topicName=HAV)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3fc52500170, createdName=12498cbcm00(暂无昵称), createdTime=Fri Mar 17 05:27:00 CST 2017, time=2017-03-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=159469, encodeId=65c51594692e, content=好资料,值得学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=124, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6KcicAVC1MwuOgo3iaicb1Imgk1yIfnvr6oXzibcAFB6puAyNJXbzWhNuLqaFYBVRWjh7rghkvFLPxMAfD5ib3nXwVD/0, createdBy=bed21972958, createdName=wxl882001, createdTime=Thu Dec 01 17:39:28 CST 2016, time=2016-12-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=159374, encodeId=fc721593e4df, content=了解一下, beContent=null, objectType=article, channel=null, level=null, likeNumber=146, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=90f31612316, createdName=xiaotaiyang1, createdTime=Thu Dec 01 11:00:52 CST 2016, time=2016-12-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1346734, encodeId=895b1346e3405, content=<a href='/topic/show?id=f20155404fc' target=_blank style='color:#2F92EE;'>#抗炎药#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=92, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55404, encryptionId=f20155404fc, topicName=抗炎药)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f49517, createdName=xinmeili, createdTime=Thu Dec 01 05:27:00 CST 2016, time=2016-12-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1424896, encodeId=2fc914248962a, content=<a href='/topic/show?id=bbd084993fd' target=_blank style='color:#2F92EE;'>#脑细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=99, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84993, encryptionId=bbd084993fd, topicName=脑细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=39a23929286, createdName=bettycmoon, createdTime=Thu Dec 01 05:27:00 CST 2016, time=2016-12-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1521862, encodeId=0695152186243, content=<a href='/topic/show?id=f83866137f' target=_blank style='color:#2F92EE;'>#EHA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6613, encryptionId=f83866137f, topicName=EHA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=937d11405368, createdName=qjddjq, createdTime=Thu Dec 01 05:27:00 CST 2016, time=2016-12-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=159007, encodeId=7dba15900edc, content=看到了希望,棒棒的, beContent=null, objectType=article, channel=null, level=null, likeNumber=123, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=7a3e1928208, createdName=顾小北大魔王, createdTime=Wed Nov 30 00:06:58 CST 2016, time=2016-11-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=158973, encodeId=cd661589e3cc, content=可以更加适合运用到临床, beContent=null, objectType=article, channel=null, level=null, likeNumber=103, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7b4c1651704, createdName=1ddcba5em94(暂无匿称), createdTime=Tue Nov 29 21:47:16 CST 2016, time=2016-11-29, status=1, ipAttribution=)]
    2016-12-01 qjddjq
  7. [GetPortalCommentsPageByObjectIdResponse(id=1947842, encodeId=103e194e8429a, content=<a href='/topic/show?id=e54d8483db' target=_blank style='color:#2F92EE;'>#HAV#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=95, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8483, encryptionId=e54d8483db, topicName=HAV)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3fc52500170, createdName=12498cbcm00(暂无昵称), createdTime=Fri Mar 17 05:27:00 CST 2017, time=2017-03-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=159469, encodeId=65c51594692e, content=好资料,值得学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=124, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6KcicAVC1MwuOgo3iaicb1Imgk1yIfnvr6oXzibcAFB6puAyNJXbzWhNuLqaFYBVRWjh7rghkvFLPxMAfD5ib3nXwVD/0, createdBy=bed21972958, createdName=wxl882001, createdTime=Thu Dec 01 17:39:28 CST 2016, time=2016-12-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=159374, encodeId=fc721593e4df, content=了解一下, beContent=null, objectType=article, channel=null, level=null, likeNumber=146, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=90f31612316, createdName=xiaotaiyang1, createdTime=Thu Dec 01 11:00:52 CST 2016, time=2016-12-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1346734, encodeId=895b1346e3405, content=<a href='/topic/show?id=f20155404fc' target=_blank style='color:#2F92EE;'>#抗炎药#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=92, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55404, encryptionId=f20155404fc, topicName=抗炎药)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f49517, createdName=xinmeili, createdTime=Thu Dec 01 05:27:00 CST 2016, time=2016-12-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1424896, encodeId=2fc914248962a, content=<a href='/topic/show?id=bbd084993fd' target=_blank style='color:#2F92EE;'>#脑细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=99, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84993, encryptionId=bbd084993fd, topicName=脑细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=39a23929286, createdName=bettycmoon, createdTime=Thu Dec 01 05:27:00 CST 2016, time=2016-12-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1521862, encodeId=0695152186243, content=<a href='/topic/show?id=f83866137f' target=_blank style='color:#2F92EE;'>#EHA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6613, encryptionId=f83866137f, topicName=EHA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=937d11405368, createdName=qjddjq, createdTime=Thu Dec 01 05:27:00 CST 2016, time=2016-12-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=159007, encodeId=7dba15900edc, content=看到了希望,棒棒的, beContent=null, objectType=article, channel=null, level=null, likeNumber=123, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=7a3e1928208, createdName=顾小北大魔王, createdTime=Wed Nov 30 00:06:58 CST 2016, time=2016-11-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=158973, encodeId=cd661589e3cc, content=可以更加适合运用到临床, beContent=null, objectType=article, channel=null, level=null, likeNumber=103, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7b4c1651704, createdName=1ddcba5em94(暂无匿称), createdTime=Tue Nov 29 21:47:16 CST 2016, time=2016-11-29, status=1, ipAttribution=)]
    2016-11-30 顾小北大魔王

    看到了希望,棒棒的

    0

  8. [GetPortalCommentsPageByObjectIdResponse(id=1947842, encodeId=103e194e8429a, content=<a href='/topic/show?id=e54d8483db' target=_blank style='color:#2F92EE;'>#HAV#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=95, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8483, encryptionId=e54d8483db, topicName=HAV)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3fc52500170, createdName=12498cbcm00(暂无昵称), createdTime=Fri Mar 17 05:27:00 CST 2017, time=2017-03-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=159469, encodeId=65c51594692e, content=好资料,值得学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=124, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6KcicAVC1MwuOgo3iaicb1Imgk1yIfnvr6oXzibcAFB6puAyNJXbzWhNuLqaFYBVRWjh7rghkvFLPxMAfD5ib3nXwVD/0, createdBy=bed21972958, createdName=wxl882001, createdTime=Thu Dec 01 17:39:28 CST 2016, time=2016-12-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=159374, encodeId=fc721593e4df, content=了解一下, beContent=null, objectType=article, channel=null, level=null, likeNumber=146, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=90f31612316, createdName=xiaotaiyang1, createdTime=Thu Dec 01 11:00:52 CST 2016, time=2016-12-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1346734, encodeId=895b1346e3405, content=<a href='/topic/show?id=f20155404fc' target=_blank style='color:#2F92EE;'>#抗炎药#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=92, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55404, encryptionId=f20155404fc, topicName=抗炎药)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f49517, createdName=xinmeili, createdTime=Thu Dec 01 05:27:00 CST 2016, time=2016-12-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1424896, encodeId=2fc914248962a, content=<a href='/topic/show?id=bbd084993fd' target=_blank style='color:#2F92EE;'>#脑细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=99, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84993, encryptionId=bbd084993fd, topicName=脑细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=39a23929286, createdName=bettycmoon, createdTime=Thu Dec 01 05:27:00 CST 2016, time=2016-12-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1521862, encodeId=0695152186243, content=<a href='/topic/show?id=f83866137f' target=_blank style='color:#2F92EE;'>#EHA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6613, encryptionId=f83866137f, topicName=EHA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=937d11405368, createdName=qjddjq, createdTime=Thu Dec 01 05:27:00 CST 2016, time=2016-12-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=159007, encodeId=7dba15900edc, content=看到了希望,棒棒的, beContent=null, objectType=article, channel=null, level=null, likeNumber=123, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=7a3e1928208, createdName=顾小北大魔王, createdTime=Wed Nov 30 00:06:58 CST 2016, time=2016-11-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=158973, encodeId=cd661589e3cc, content=可以更加适合运用到临床, beContent=null, objectType=article, channel=null, level=null, likeNumber=103, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7b4c1651704, createdName=1ddcba5em94(暂无匿称), createdTime=Tue Nov 29 21:47:16 CST 2016, time=2016-11-29, status=1, ipAttribution=)]
    2016-11-29 1ddcba5em94(暂无匿称)

    可以更加适合运用到临床

    0

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脑卒中是全球最主要的致死病因之一,亦是最主要的疾病负担;我国是脑卒中高发国家之一,且发病率以每年8.7%的速率上升,发病者约30%死亡,生存者亦或伴有偏瘫、失语等残障。我国2008年的居民死因抽样调查显示,脑卒中已成为我国国民第一位的死亡原因。因此,脑卒中的防治尤为重要。这里小M整理了近期脑卒中亮点研究进展与大家分享。【1】Stroke:血液透析患者血清磷水平与脑卒中风险的关系透析患者血清磷酸

Heart Rhythm:荟萃分析显示,亚洲患者更常用标准剂量的NOACs,且疗效较优

背景:尽管随机对照试验(RCTs)表明标准剂量的非维生素K拮抗剂口服抗凝剂(NOACs)更引人注目,但是在亚洲临床实践中,低剂量NOACs更常用。目的:研究者评估纳入RCTs的亚洲人群,标志剂量VS低剂量NOACs的相对疗效及风险。方法:研究者对RE-LY和ENGAGE AF-TIMI48研究中应用NOACs的3155个亚洲患者进行预先指定的荟萃分析。在随机效应模型,应用风险比(RR)和95%可信

Stroke:中国成人抑郁发作与卒中风险的相关性研究

这个大型的前瞻性研究表明,重性抑郁发作的存在是卒中的一个危险因素,尤其是在吸烟者群体中更为明显。

小心这4种用药错误,易导致脑卒中

一、解热镇痛药有的患者用阿司匹林、扑热息痛等进行退热,这类药会促使人体大量出汗,使体温下降。伴有呕吐、腹泻的中年患者,发汗后会致使机体严重缺水,使血液浓缩,增加黏滞性,致血栓形成。二、促凝血药当中年人发生血性疾病时,常会使用止血敏、安络血等促凝血的药物来止血。而这些药物如使用过量,会促使血栓的形成。患有脑动脉硬化,血脂偏高的中年患者,血液极易凝固,形成血栓,会发生脑卒中。三、利尿药速尿、双氢克尿塞

Stroke:血液透析患者血清磷水平与脑卒中风险的关系

研究结果表明较高的血清磷酸盐水平与脑出血的风险增加有关,而低水平与血液透析患者的脑梗塞风险增加有关。因此,将血液透析患者的血清磷酸盐水平控制在一个适当的范围很重要。

Neurology:急性脑卒中患者鼻饲管与肺炎、临床结局的关系

由此可见,早期插入鼻饲管不会增加卒中后肺炎发病率、死亡率和较差功能预后,它可安全用于急性卒中患者。

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