Biomed Pharmacother:中药复方菩人丹可减轻老年2型糖尿病大鼠非酒精性脂肪性肝病

2022-03-22 紫菀款冬 MedSci原创

探讨中药复方菩人丹治疗老年2型糖尿病合并非酒精性脂肪性肝病大鼠的疗效及机理

背景:老年人更容易出现胰岛素抵抗和脂质代谢紊乱非酒精性脂肪性肝病(NAFLD)是2型糖尿病(T2DM)最典型的并发症之一。T2DM是NAFLD的一个强而独立的危险因素,二者相互影响,导致死亡风险升高。

菩人丹(PRD)是经临床验证的中药复方,由苦瓜、人参、丹参、葛根、制首乌组成,具有益气养阴清热、活血化瘀通络之功效。据报道,苦瓜是PRD的主要药物,具有改善胰岛素敏感性显著的降脂作用。此外,PRD可有效改善T2DM大鼠的血脂异常,对T2DM大鼠的视网膜病变和大血管病变具有明显的保护作用。提示PRD可用于T2DM患者合并NAFLD的治疗。

目的:探讨PRD治疗老年T2DM合并NAFLD大鼠的疗效及机理。

方法:采用高脂饮食(HFD)喂养大鼠(13月龄),腹腔注射STZ(20 mg/kg)复制T2DM模型。造模成功的糖尿病大鼠分为5组:模型组(蒸馏水);二甲双胍阳性对照组(盐酸二甲双胍片0.14 g/kg/d);PRD低剂量组(3.375 g/kg/d);PRD中剂量组(6.75 g/kg/d);PRD高剂量组(13.5 g/kg/d)。

给药后采集血液和肝组织标本,测量血糖、胰岛素等糖代谢指标,以及TC、TG、LDL、HDL、FFA等脂代谢指标HE染色油红O染色观察肝脏脂肪积累情况。Western Blot检测mTOR、p-mTOR、S6K1、p-S6K1、SREBP-1c蛋白表达水平。

结果:经PRD治疗后,不仅胰岛素敏感性和胰岛素抵抗明显改善,血清TC、TG、LDL、FFA、AST、ALT及肝组织脂质积累也明显减少。此外,PRD显著下调肝脏组织中p-mTOR、p-S6K1和SREBP-1c的表达

结论:PRD可通过抑制mTOR /S6K1/ SREBP-1c通路缓解老年T2DM大鼠NAFLD。该研究为2型糖尿病合并非酒精性脂肪性肝病的治疗提供了方向。但该研究仍存在一些局限性——在分子机理的探索中,未添加抑制剂。此外,胰岛素抵抗是否为T2DM大鼠NAFLD的核心机制还需要进一步的实验验证,而在PRD中发挥治疗作用的有效物质还有待后续实验的验证。

文献来源:

Fan L, Niu H, Zhao L, et al. Purendan alleviates non-alcoholic fatty liver disease in aged type 2 diabetic rats via regulating mTOR/S6K1/SREBP-1c signaling pathway. Biomed Pharmacother. 2022;148:112697. doi:10.1016/j.biopha.2022.112697

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    2022-04-20 yb6560
  4. 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status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1611505, encodeId=286616115051c, content=<a href='/topic/show?id=eb6b1145939' target=_blank style='color:#2F92EE;'>#Med#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11459, encryptionId=eb6b1145939, topicName=Med)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=552a19396740, createdName=ms3994565386320060, createdTime=Thu Mar 24 12:51:23 CST 2022, time=2022-03-24, status=1, ipAttribution=)]
    2022-09-17 qjddjq
  5. [GetPortalCommentsPageByObjectIdResponse(id=1654067, encodeId=e14c165406e33, content=<a href='/topic/show?id=1e1584351b2' target=_blank style='color:#2F92EE;'>#脂肪性肝病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84351, encryptionId=1e1584351b2, topicName=脂肪性肝病)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c46224431741, createdName=wwzzly, createdTime=Tue May 17 09:51:23 CST 2022, time=2022-05-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1673739, encodeId=1dbf16e37390c, content=<a href='/topic/show?id=757b954e922' target=_blank style='color:#2F92EE;'>#酒精性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=95479, encryptionId=757b954e922, topicName=酒精性)], attachment=null, authenticateStatus=null, createdAvatar=null, 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status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1611505, encodeId=286616115051c, content=<a href='/topic/show?id=eb6b1145939' target=_blank style='color:#2F92EE;'>#Med#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11459, encryptionId=eb6b1145939, topicName=Med)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=552a19396740, createdName=ms3994565386320060, createdTime=Thu Mar 24 12:51:23 CST 2022, time=2022-03-24, status=1, ipAttribution=)]
  6. [GetPortalCommentsPageByObjectIdResponse(id=1654067, encodeId=e14c165406e33, content=<a href='/topic/show?id=1e1584351b2' target=_blank style='color:#2F92EE;'>#脂肪性肝病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84351, encryptionId=1e1584351b2, topicName=脂肪性肝病)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c46224431741, createdName=wwzzly, createdTime=Tue May 17 09:51:23 CST 2022, time=2022-05-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1673739, encodeId=1dbf16e37390c, content=<a href='/topic/show?id=757b954e922' target=_blank style='color:#2F92EE;'>#酒精性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=95479, encryptionId=757b954e922, topicName=酒精性)], attachment=null, authenticateStatus=null, createdAvatar=null, 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status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1611505, encodeId=286616115051c, content=<a href='/topic/show?id=eb6b1145939' target=_blank style='color:#2F92EE;'>#Med#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11459, encryptionId=eb6b1145939, topicName=Med)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=552a19396740, createdName=ms3994565386320060, createdTime=Thu Mar 24 12:51:23 CST 2022, time=2022-03-24, status=1, ipAttribution=)]
    2022-09-25 sunylz
  7. 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    2022-08-23 jj000001
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