Front Pharmacol:琥珀安神汤通过激活PI3K/AKT通路促进创伤性脑损伤大鼠的骨折愈合

2022-09-16 紫菀款冬 MedSci原创

探索琥珀安神汤(HPASD)治疗创伤性脑损伤大鼠骨折愈合的药理机制。

背景:琥珀安神汤(HPASD)琥珀、朱砂、煅龙齿、菊花、冬桑叶组成,由已故教授陆银华(中国浙江省浙江中医药大学第一附属医院)提出,是一种临床用于治疗脑震荡并促进桡骨远端骨折愈合的药物,但其药理机制尚不清楚。

 

方法:采用超高效液相色谱-四极飞行时间质谱(UPLC/Q-TOF MS)分析HPASD的主要活性成分。将大鼠随机分为骨折组骨折合并创伤性脑损伤组(FBI)和FBI合并HPASD治疗组(FBIH)。FBIH组大鼠连续14天或21天口服HPASD(2.4 g/kg、4.8 g/kg和9.6 g/kg)。

通过射线分析和微米级计算机断层扫描(micro-CT)分析确定骨折骨痂形成和骨折部位。H&E染色和三点弯曲试验分别用于评估组织学损伤和生物力学特性。通过酶联免疫吸附试验(ELISA)、定量逆转录聚合酶链反应(qRT PCR)或蛋白免疫印迹试验分别测定与骨形成和分化相关的细胞因子/蛋白以及PI3K/AKT通路相关蛋白的水平。此外还进行了基于UPLC-Q/TOF MS的血清代谢组学分析,以研究HPASD治疗FBI的疗效。

结果:UPLC/Q-TOF MS分析显示了HPASD中的化学成分,包括类黄酮、氨基酸、皂甙和苯丙类成分等。HPASD剂量依赖性地促进骨痂形成,增加骨密度,改善机械参数和形态学评分,并促进VEGF、PDGF、bFGF、VEGFA、CoL1A1、RUNX2、BMP2和聚集蛋白聚糖的表达,抑制MMP13的表达,激活PI3K/AKT通路。代谢组学分析显示苹果酸-天冬氨酸穿梭和葡萄糖-丙氨酸异常。

结论:HPASD通过促进骨形成和调节苹果酸穿梭和葡萄糖-丙氨酸循环加速骨折愈合,这可能与PI3K/AKT通路的激活有关

 

文献来源:

Shen J, Li YZ, Yao S, et al. Hu'po Anshen Decoction Accelerated Fracture-Healing in a Rat Model of Traumatic Brain Injury Through Activation of PI3K/AKT Pathway. Front Pharmacol. 2022;13:952696. Published 2022 Jul 18. doi:10.3389/fphar.2022.952696

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    2022-10-05 jj000001
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createdName=yb6560, createdTime=Sun Dec 25 19:59:01 CST 2022, time=2022-12-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1787834, encodeId=f82e1e8783422, content=<a href='/topic/show?id=fa03141591e' target=_blank style='color:#2F92EE;'>#Pharm#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14159, encryptionId=fa03141591e, topicName=Pharm)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8942242, createdName=jj000001, createdTime=Wed Oct 05 16:59:01 CST 2022, time=2022-10-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1908740, encodeId=f9891908e4015, content=<a href='/topic/show?id=a8d0141605e' target=_blank style='color:#2F92EE;'>#pharma#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14160, 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objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14162, encryptionId=38e014162e2, topicName=Pharmacol)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=930e243, createdName=dingxiaobo, createdTime=Thu Oct 20 01:59:01 CST 2022, time=2022-10-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1656210, encodeId=515c1656210c9, content=<a href='/topic/show?id=f4782246ec' target=_blank style='color:#2F92EE;'>#Akt#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2246, encryptionId=f4782246ec, topicName=Akt)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b8c724776724, createdName=xfpan20, createdTime=Sat Mar 18 22:59:01 CST 2023, time=2023-03-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1689142, 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createdAvatar=http://thirdqq.qlogo.cn/qqapp/101296147/BF4BC9769C2FF12AC93CAA0069C0696C/100, createdBy=7bb22500091, createdName=ms1292405679162969, createdTime=Fri Sep 16 15:59:01 CST 2022, time=2022-09-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1335417, encodeId=cdad133541ed4, content=<a href='/topic/show?id=e7cc32022c7' target=_blank style='color:#2F92EE;'>#创伤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=32022, encryptionId=e7cc32022c7, topicName=创伤)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=aa5a2500103, createdName=ms920641618706883, createdTime=Fri Sep 16 15:59:01 CST 2022, time=2022-09-16, status=1, ipAttribution=)]
  5. [GetPortalCommentsPageByObjectIdResponse(id=2025551, encodeId=4f6a20255513a, content=<a href='/topic/show?id=66f93204223' target=_blank style='color:#2F92EE;'>#创伤性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=32042, encryptionId=66f93204223, topicName=创伤性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=325a197, createdName=amyloid, createdTime=Thu Dec 15 06:59:01 CST 2022, time=2022-12-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1996514, encodeId=13a219965149b, content=<a href='/topic/show?id=ed881120ec8' target=_blank style='color:#2F92EE;'>#MAC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11207, encryptionId=ed881120ec8, topicName=MAC)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4b65161, createdName=yb6560, createdTime=Sun Dec 25 19:59:01 CST 2022, time=2022-12-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1787834, encodeId=f82e1e8783422, content=<a href='/topic/show?id=fa03141591e' target=_blank style='color:#2F92EE;'>#Pharm#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14159, encryptionId=fa03141591e, topicName=Pharm)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8942242, createdName=jj000001, createdTime=Wed Oct 05 16:59:01 CST 2022, time=2022-10-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1908740, encodeId=f9891908e4015, content=<a href='/topic/show?id=a8d0141605e' target=_blank style='color:#2F92EE;'>#pharma#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14160, 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objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14162, encryptionId=38e014162e2, topicName=Pharmacol)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=930e243, createdName=dingxiaobo, createdTime=Thu Oct 20 01:59:01 CST 2022, time=2022-10-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1656210, encodeId=515c1656210c9, content=<a href='/topic/show?id=f4782246ec' target=_blank style='color:#2F92EE;'>#Akt#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2246, encryptionId=f4782246ec, topicName=Akt)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b8c724776724, createdName=xfpan20, createdTime=Sat Mar 18 22:59:01 CST 2023, time=2023-03-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1689142, encodeId=e0fb168914270, content=<a href='/topic/show?id=b8ac10168e8b' target=_blank style='color:#2F92EE;'>#骨折愈合#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=101687, encryptionId=b8ac10168e8b, topicName=骨折愈合)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ce4c28733108, createdName=HinsMax, createdTime=Sat Apr 29 01:59:01 CST 2023, time=2023-04-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1333256, encodeId=6a4d1333256d2, content=<a href='/topic/show?id=ecfa1423117' target=_blank style='color:#2F92EE;'>#PI3K#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14231, encryptionId=ecfa1423117, topicName=PI3K)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/qqapp/101296147/BF4BC9769C2FF12AC93CAA0069C0696C/100, createdBy=7bb22500091, createdName=ms1292405679162969, createdTime=Fri Sep 16 15:59:01 CST 2022, time=2022-09-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1335417, encodeId=cdad133541ed4, content=<a href='/topic/show?id=e7cc32022c7' target=_blank style='color:#2F92EE;'>#创伤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=32022, encryptionId=e7cc32022c7, topicName=创伤)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=aa5a2500103, createdName=ms920641618706883, createdTime=Fri Sep 16 15:59:01 CST 2022, time=2022-09-16, status=1, ipAttribution=)]
    2023-04-28 lidong40
  6. [GetPortalCommentsPageByObjectIdResponse(id=2025551, encodeId=4f6a20255513a, content=<a href='/topic/show?id=66f93204223' target=_blank style='color:#2F92EE;'>#创伤性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=32042, encryptionId=66f93204223, topicName=创伤性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=325a197, createdName=amyloid, createdTime=Thu Dec 15 06:59:01 CST 2022, time=2022-12-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1996514, encodeId=13a219965149b, content=<a href='/topic/show?id=ed881120ec8' target=_blank style='color:#2F92EE;'>#MAC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11207, encryptionId=ed881120ec8, topicName=MAC)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4b65161, 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  7. 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    2023-03-18 xfpan20
  8. 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  9. 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