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DIABETOLOGIA:DPP-4抑制剂利格列汀抗血管生成作用是通过抑制氧诱导视网膜病变小鼠模型中VEGFR信号通路实现的?

2018-12-23 MedSci MedSci原创

利格列汀对视网膜神经血管单位具有保护作用,但在增生性视网膜病变中,二肽基肽酶4(DPP-4)抑制作用可能是有害的。本研究的目的是评估利格列汀对缺血诱导的视网膜新生血管形成的影响。 研究人员使用C57BL / 6J和胰高血糖素样肽1(GLP-1)受体(Glp1r)- / -小鼠经受氧诱导的视网膜病变(OIR)模型。在出生后第12至16天用利格列汀对两个模型皮下处理。未注射的OIR和未暴露的小鼠

利格列汀对视网膜神经血管单位具有保护作用,但在增生性视网膜病变中,二肽基肽酶4DPP-4)抑制作用可能是有害的。本研究的目的是评估利格列汀对缺血诱导的视网膜新生血管形成的影响。

研究人员使用C57BL / 6J和胰高血糖素样肽1GLP-1)受体(Glp1r- / -小鼠经受氧诱导的视网膜病变(OIR)模型。在出生后第1216天用利格列汀对两个模型皮下处理。未注射的OIR和未暴露的小鼠作为对照。对全身水平毛细管增生和活性GLP-1进行定量。使用蛋白质印迹法评估利格列汀对血管内皮生长因子(VEGF)诱导的下游信号传导的影响,用于视网膜磷酸化细胞外信号调节激酶(ERK1/2和视网膜基因表达分析。

结果显示,与对照组相比,利格列汀治疗导致OIR小鼠中活性GLP-1增加和新生血管核数量减少(-30%,p  <0.05)。由于C57BL / 6JGlp1r - / -小鼠的新血管形成减少相似,因此利格列汀的抗血管生成作用与GLP-1R状态无关。Vegf的表达(也称为VEGFA)和HIF1AC57BL / 6J小鼠OIR利拉列汀后处理增加(p  <0.05p  <0.01)。在HUVEC中,利格列汀抑制VEGF诱导的丝裂原活化蛋白激酶(MAPK/ ERK的增加(-67%,p <0.001)和MAPK / c-Jun N-末端激酶(JNK)( - 13%,p  <0.05)途径活性。在C57BL / 6J小鼠的视网膜中,利格列汀治疗后p-ERK1 / 2水平显著降低(-47%,p  <0.05)。

利格列汀的系统治疗证明了由VEGF受体下游信号传导的抑制介导的GLP-1R非依赖性抗血管生成作用。利格列汀对糖尿病视网膜病变的特异性作用对于患有糖尿病的个体具有潜在的益处,而与代谢作用无关。

原始出处:

Matthias Kolibabka, Nadine Dietrich, Thomas Klein,Anti-angiogenic effects of the DPP-4 inhibitor linagliptin via inhibition of VEGFR signalling in the mouse model of oxygen-induced retinopathy

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attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b12d13147749, createdName=wgx310, createdTime=Tue Dec 25 08:41:00 CST 2018, time=2018-12-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1436789, encodeId=59891436e8949, content=<a href='/topic/show?id=a9424e199a5' target=_blank style='color:#2F92EE;'>#小鼠模型#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=47199, encryptionId=a9424e199a5, topicName=小鼠模型)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Tue Dec 25 08:41:00 CST 2018, time=2018-12-25, status=1, ipAttribution=)]
    2019-06-23 jklm09
  4. 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08:41:00 CST 2018, time=2018-12-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1545646, encodeId=d38c1545646fe, content=<a href='/topic/show?id=4dd155e701f' target=_blank style='color:#2F92EE;'>#抗血管生成#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=110, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55770, encryptionId=4dd155e701f, topicName=抗血管生成)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=608413807146, createdName=12498bd5m20暂无昵称, createdTime=Tue Dec 25 08:41:00 CST 2018, time=2018-12-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1539714, encodeId=f9e11539e1434, content=<a href='/topic/show?id=c61a2e315da' target=_blank style='color:#2F92EE;'>#信号通路#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=88, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=27315, encryptionId=c61a2e315da, topicName=信号通路)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b12d13147749, createdName=wgx310, createdTime=Tue Dec 25 08:41:00 CST 2018, time=2018-12-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1436789, encodeId=59891436e8949, content=<a href='/topic/show?id=a9424e199a5' target=_blank style='color:#2F92EE;'>#小鼠模型#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=47199, encryptionId=a9424e199a5, topicName=小鼠模型)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Tue Dec 25 08:41:00 CST 2018, time=2018-12-25, status=1, ipAttribution=)]
  5. 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encryptionId=afda591646, topicName=DIA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=987022654425, createdName=ms9608593228839890, createdTime=Wed Sep 25 05:41:00 CST 2019, time=2019-09-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1973554, encodeId=ab0f19e35547c, content=<a href='/topic/show?id=3ebb3230614' target=_blank style='color:#2F92EE;'>#利格列汀#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=104, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=32306, encryptionId=3ebb3230614, topicName=利格列汀)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/OKNjeqMuGQiclFVAJtO8Yvicr3uMFOHysUY3EYJses2g3YQKBAT7FzaJwAfeVrbPEPnsiaBAicMAJX7icLdcxzMj0kA/132, createdBy=038e2500100, createdName=ms7517674339485982, createdTime=Sat May 18 09:41:00 CST 2019, time=2019-05-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1784699, encodeId=a7021e846992d, content=<a href='/topic/show?id=6a926214b8' target=_blank style='color:#2F92EE;'>#DPP-4抑制#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=97, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6214, encryptionId=6a926214b8, topicName=DPP-4抑制)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d139492, createdName=xue8602, createdTime=Tue Aug 20 18:41:00 CST 2019, time=2019-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1534406, encodeId=96551534406db, content=<a href='/topic/show?id=22b3e9887e' target=_blank style='color:#2F92EE;'>#GFR#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7988, encryptionId=22b3e9887e, topicName=GFR)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0a812532020, createdName=liuyiping, createdTime=Tue Dec 25 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attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b12d13147749, createdName=wgx310, createdTime=Tue Dec 25 08:41:00 CST 2018, time=2018-12-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1436789, encodeId=59891436e8949, content=<a href='/topic/show?id=a9424e199a5' target=_blank style='color:#2F92EE;'>#小鼠模型#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=47199, encryptionId=a9424e199a5, topicName=小鼠模型)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Tue Dec 25 08:41:00 CST 2018, time=2018-12-25, status=1, ipAttribution=)]
  6. [GetPortalCommentsPageByObjectIdResponse(id=1760952, encodeId=19c51e60952c9, content=<a href='/topic/show?id=9bea33520d' target=_blank style='color:#2F92EE;'>#BET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=109, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3352, encryptionId=9bea33520d, topicName=BET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9a1a37427546, createdName=ms5439512287675881, createdTime=Tue Sep 10 05:41:00 CST 2019, time=2019-09-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1932962, encodeId=c6ae1932962e7, content=<a href='/topic/show?id=6b1255e66ba' target=_blank style='color:#2F92EE;'>#抗血管#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=105, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55766, encryptionId=6b1255e66ba, topicName=抗血管)], attachment=null, authenticateStatus=null, createdAvatar=, 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encodeId=a7021e846992d, content=<a href='/topic/show?id=6a926214b8' target=_blank style='color:#2F92EE;'>#DPP-4抑制#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=97, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6214, encryptionId=6a926214b8, topicName=DPP-4抑制)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d139492, createdName=xue8602, createdTime=Tue Aug 20 18:41:00 CST 2019, time=2019-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1534406, encodeId=96551534406db, content=<a href='/topic/show?id=22b3e9887e' target=_blank style='color:#2F92EE;'>#GFR#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7988, encryptionId=22b3e9887e, topicName=GFR)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0a812532020, createdName=liuyiping, createdTime=Tue Dec 25 08:41:00 CST 2018, time=2018-12-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1545646, encodeId=d38c1545646fe, content=<a href='/topic/show?id=4dd155e701f' target=_blank style='color:#2F92EE;'>#抗血管生成#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=110, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55770, encryptionId=4dd155e701f, topicName=抗血管生成)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=608413807146, createdName=12498bd5m20暂无昵称, createdTime=Tue Dec 25 08:41:00 CST 2018, time=2018-12-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1539714, encodeId=f9e11539e1434, content=<a href='/topic/show?id=c61a2e315da' target=_blank style='color:#2F92EE;'>#信号通路#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=88, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=27315, encryptionId=c61a2e315da, topicName=信号通路)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b12d13147749, createdName=wgx310, createdTime=Tue Dec 25 08:41:00 CST 2018, time=2018-12-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1436789, encodeId=59891436e8949, content=<a href='/topic/show?id=a9424e199a5' target=_blank style='color:#2F92EE;'>#小鼠模型#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=47199, encryptionId=a9424e199a5, topicName=小鼠模型)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Tue Dec 25 08:41:00 CST 2018, time=2018-12-25, status=1, ipAttribution=)]
  7. [GetPortalCommentsPageByObjectIdResponse(id=1760952, encodeId=19c51e60952c9, content=<a href='/topic/show?id=9bea33520d' target=_blank style='color:#2F92EE;'>#BET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=109, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3352, encryptionId=9bea33520d, topicName=BET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9a1a37427546, createdName=ms5439512287675881, createdTime=Tue Sep 10 05:41:00 CST 2019, time=2019-09-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1932962, encodeId=c6ae1932962e7, content=<a href='/topic/show?id=6b1255e66ba' target=_blank style='color:#2F92EE;'>#抗血管#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=105, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55766, encryptionId=6b1255e66ba, topicName=抗血管)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=9fe6351, createdName=flyingeagle77, createdTime=Thu Jan 31 21:41:00 CST 2019, time=2019-01-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1851872, encodeId=d6e818518e2b9, content=<a href='/topic/show?id=f0a254918f0' target=_blank style='color:#2F92EE;'>#抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=96, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54918, encryptionId=f0a254918f0, topicName=抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Sun Jun 23 00:41:00 CST 2019, time=2019-06-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1638921, encodeId=8baf16389219c, content=<a href='/topic/show?id=afda591646' target=_blank style='color:#2F92EE;'>#DIA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=97, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5916, encryptionId=afda591646, topicName=DIA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=987022654425, createdName=ms9608593228839890, createdTime=Wed Sep 25 05:41:00 CST 2019, time=2019-09-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1973554, encodeId=ab0f19e35547c, content=<a href='/topic/show?id=3ebb3230614' target=_blank style='color:#2F92EE;'>#利格列汀#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=104, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=32306, encryptionId=3ebb3230614, topicName=利格列汀)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/OKNjeqMuGQiclFVAJtO8Yvicr3uMFOHysUY3EYJses2g3YQKBAT7FzaJwAfeVrbPEPnsiaBAicMAJX7icLdcxzMj0kA/132, createdBy=038e2500100, createdName=ms7517674339485982, createdTime=Sat May 18 09:41:00 CST 2019, time=2019-05-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1784699, encodeId=a7021e846992d, content=<a href='/topic/show?id=6a926214b8' target=_blank style='color:#2F92EE;'>#DPP-4抑制#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=97, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6214, encryptionId=6a926214b8, topicName=DPP-4抑制)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d139492, createdName=xue8602, createdTime=Tue Aug 20 18:41:00 CST 2019, time=2019-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1534406, encodeId=96551534406db, content=<a href='/topic/show?id=22b3e9887e' target=_blank style='color:#2F92EE;'>#GFR#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7988, encryptionId=22b3e9887e, topicName=GFR)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0a812532020, createdName=liuyiping, createdTime=Tue Dec 25 08:41:00 CST 2018, time=2018-12-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1545646, encodeId=d38c1545646fe, content=<a href='/topic/show?id=4dd155e701f' target=_blank style='color:#2F92EE;'>#抗血管生成#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=110, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55770, encryptionId=4dd155e701f, topicName=抗血管生成)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=608413807146, createdName=12498bd5m20暂无昵称, createdTime=Tue Dec 25 08:41:00 CST 2018, time=2018-12-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1539714, encodeId=f9e11539e1434, content=<a href='/topic/show?id=c61a2e315da' target=_blank style='color:#2F92EE;'>#信号通路#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=88, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=27315, encryptionId=c61a2e315da, topicName=信号通路)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b12d13147749, createdName=wgx310, createdTime=Tue Dec 25 08:41:00 CST 2018, time=2018-12-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1436789, encodeId=59891436e8949, content=<a href='/topic/show?id=a9424e199a5' target=_blank style='color:#2F92EE;'>#小鼠模型#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=47199, encryptionId=a9424e199a5, topicName=小鼠模型)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Tue Dec 25 08:41:00 CST 2018, time=2018-12-25, status=1, ipAttribution=)]
    2018-12-25 liuyiping
  8. 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encryptionId=afda591646, topicName=DIA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=987022654425, createdName=ms9608593228839890, createdTime=Wed Sep 25 05:41:00 CST 2019, time=2019-09-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1973554, encodeId=ab0f19e35547c, content=<a href='/topic/show?id=3ebb3230614' target=_blank style='color:#2F92EE;'>#利格列汀#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=104, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=32306, encryptionId=3ebb3230614, topicName=利格列汀)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/OKNjeqMuGQiclFVAJtO8Yvicr3uMFOHysUY3EYJses2g3YQKBAT7FzaJwAfeVrbPEPnsiaBAicMAJX7icLdcxzMj0kA/132, createdBy=038e2500100, createdName=ms7517674339485982, createdTime=Sat May 18 09:41:00 CST 2019, time=2019-05-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1784699, encodeId=a7021e846992d, content=<a href='/topic/show?id=6a926214b8' target=_blank style='color:#2F92EE;'>#DPP-4抑制#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=97, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6214, encryptionId=6a926214b8, topicName=DPP-4抑制)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d139492, createdName=xue8602, createdTime=Tue Aug 20 18:41:00 CST 2019, time=2019-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1534406, encodeId=96551534406db, content=<a href='/topic/show?id=22b3e9887e' target=_blank style='color:#2F92EE;'>#GFR#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7988, encryptionId=22b3e9887e, topicName=GFR)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0a812532020, createdName=liuyiping, createdTime=Tue Dec 25 08:41:00 CST 2018, time=2018-12-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1545646, encodeId=d38c1545646fe, content=<a href='/topic/show?id=4dd155e701f' target=_blank style='color:#2F92EE;'>#抗血管生成#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=110, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55770, encryptionId=4dd155e701f, topicName=抗血管生成)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=608413807146, createdName=12498bd5m20暂无昵称, createdTime=Tue Dec 25 08:41:00 CST 2018, time=2018-12-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1539714, encodeId=f9e11539e1434, content=<a href='/topic/show?id=c61a2e315da' target=_blank style='color:#2F92EE;'>#信号通路#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=88, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=27315, encryptionId=c61a2e315da, topicName=信号通路)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b12d13147749, createdName=wgx310, createdTime=Tue Dec 25 08:41:00 CST 2018, time=2018-12-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1436789, encodeId=59891436e8949, content=<a href='/topic/show?id=a9424e199a5' target=_blank style='color:#2F92EE;'>#小鼠模型#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=47199, encryptionId=a9424e199a5, topicName=小鼠模型)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Tue Dec 25 08:41:00 CST 2018, time=2018-12-25, status=1, ipAttribution=)]
  9. 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encryptionId=afda591646, topicName=DIA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=987022654425, createdName=ms9608593228839890, createdTime=Wed Sep 25 05:41:00 CST 2019, time=2019-09-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1973554, encodeId=ab0f19e35547c, content=<a href='/topic/show?id=3ebb3230614' target=_blank style='color:#2F92EE;'>#利格列汀#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=104, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=32306, encryptionId=3ebb3230614, topicName=利格列汀)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/OKNjeqMuGQiclFVAJtO8Yvicr3uMFOHysUY3EYJses2g3YQKBAT7FzaJwAfeVrbPEPnsiaBAicMAJX7icLdcxzMj0kA/132, createdBy=038e2500100, createdName=ms7517674339485982, createdTime=Sat May 18 09:41:00 CST 2019, time=2019-05-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1784699, encodeId=a7021e846992d, content=<a href='/topic/show?id=6a926214b8' target=_blank style='color:#2F92EE;'>#DPP-4抑制#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=97, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6214, encryptionId=6a926214b8, topicName=DPP-4抑制)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d139492, createdName=xue8602, createdTime=Tue Aug 20 18:41:00 CST 2019, time=2019-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1534406, encodeId=96551534406db, content=<a href='/topic/show?id=22b3e9887e' target=_blank style='color:#2F92EE;'>#GFR#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7988, encryptionId=22b3e9887e, topicName=GFR)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0a812532020, createdName=liuyiping, createdTime=Tue Dec 25 08:41:00 CST 2018, time=2018-12-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1545646, encodeId=d38c1545646fe, content=<a href='/topic/show?id=4dd155e701f' target=_blank style='color:#2F92EE;'>#抗血管生成#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=110, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55770, encryptionId=4dd155e701f, topicName=抗血管生成)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=608413807146, createdName=12498bd5m20暂无昵称, createdTime=Tue Dec 25 08:41:00 CST 2018, time=2018-12-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1539714, encodeId=f9e11539e1434, content=<a href='/topic/show?id=c61a2e315da' target=_blank style='color:#2F92EE;'>#信号通路#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=88, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=27315, encryptionId=c61a2e315da, topicName=信号通路)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b12d13147749, createdName=wgx310, createdTime=Tue Dec 25 08:41:00 CST 2018, time=2018-12-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1436789, encodeId=59891436e8949, content=<a href='/topic/show?id=a9424e199a5' target=_blank style='color:#2F92EE;'>#小鼠模型#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=47199, encryptionId=a9424e199a5, topicName=小鼠模型)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Tue Dec 25 08:41:00 CST 2018, time=2018-12-25, status=1, ipAttribution=)]
  10. 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