客户研究进展︱发现抑制化疗药物副作用潜在靶点

2020NIAN12YUE12RI,ANHUIYIKEDAXUEYAOXUEYUANDEHUANGCHENGFUJIAOSHOUYUMATAOTAOFUJIAOSHOUZUOWEIGONGTONGTONGXUNZUOZHEZAI《Cell Death & Disease》ZAZHISHANGFABIAOLETIWEI《PSTPIP2 inhibits cisplatin-indu

ced acute kidney injury by suppressing apoptosis of renal tubular epithelial cells》DEZHANGPIANYANJIULUNWEN,JI“PSTPIP2TONGGUOYIZHISHENXIAOGUANSHANGPIXIBAODIAOWANGYIZHISHUNBOYOUDAODEJIXINGSHENSUNSHANG”。

 

ZHIDEYITIDESHI,WENZHONGYONGDAOLEHANHENGSHENGWUTIGONGDEXIANXIANGGUANBINGDUHEXIAOGANRAORNA。

 

SHUNBOSHIZHILIAOGEZHONGLEIXINGDERENLEIAIZHENGZUICHANGYONGHEGAOXIAODEHUALIAOYAOWUZHIYI,BUXINGDESHI,SHUNBODELINCHUANGYINGYONGSHOUDAOYUSHENDUXINGXIANGGUANDEDALIANGFUZUOYONGDEYANZHONGXIANZHI,SHENDUXINGSHISHUNBOZUICHANGJIANDEFUZUOYONGZHIYI。YINCI,GENJUSHUNBOSHENDUXINGDEJIZHIXUNZHAOYIZHONGYOUXIAODEZHILIAOFANGFAPOZAIMEIJIE。WOMENJIANYAOKANXIAZHEIPIANWENZHANGDAODIZAIYIZHIHUALIAOYAOWUSHUNBOYOUDAOAKIDEJIZHISHANGYOUSHENMETUPOXINGJINZHANNI?

 

 

Part 1 

 

HUANGCHENGFUJIAOSHOUYUMATAOTAOFUJIAOSHOUZHANGQICONGSHIKANGYANMIANYIYAOLIXUE、FENZIYAOLIXUEYIJIGAISHANGANSHENGONGNENGDEZHONGYAODEXINYAOYANJIU、MANXINGSHENBINGDEFABINGJIZHIYANJIUYIJIZHONGYAOJINGFANGYOUXIAOBUWEIDEBAXIANGSHAIXUANDENGYANJIU,JINNIANLAIZAITheranostics、Cancer Lett、Journal of Proteomics、Cell Death & DiseaseDENGZAZHIFABIAOLUNWEN,JIESHILEYIZHIZUDANBAIH3K27YIXIANHUAXIEDIAOBAIXIBAOJIESU9JIEDAOSHUNBOYOUDAODEJIXINGSHENSUNSHANGZHONGFAHUIKANGYANZUOYONG,ZUDANBAIQUYIXIANHUAMEI2YIZHIBMP-7CUJINJIXINGSHENSUNSHANGSHENXIAOGUANSHANGPIXIBAODIAOWANGYIJI18β-GANCAOCISUANTONGGUOBAXIANGHDAC2ZENGQIANGBMP-7YIZHISHENXIAOGUANSHANGPIXIBAODIAOWANGDENG。

 

SHUNBO(Cisplatin,CP)SHIYIZHONGYOUXIAODEHUALIAOYAOWU,GUANGFANYINGYONGYUGEZHONGSHITIZHONGLIUDEZHILIAO。RANER,CPDESHENDUXINGSHIQIYINGYONGDEYIGEZHONGYAOXIANZHIYINSU,MUQIANSHANGWUGAISHANCPSUOZHIJIXINGSHENSUNSHANG(acute kidney injury,AKI)DEFANGFA。BENWENYANJIULEFUANSUAN-SIANSUAN-SUANSUANLINSUANMEIXIANGHUZUOYONGDANBAI2(PSTPIP2)ZAICPYOUDAODEAKIZHONGDETESHUZUOYONG。ZHENGSHILEPSTPIP2KEZUOWEIYUFANGSHUNBOSHENDUXINGDEQIANZAIBADIAN。XIAMIANGENZHEXIAOHENGYIQILAIYANDUYIXIAZHEIPIANWENZHANGBA。

 

Part  2

 

WEILETANJIUPSTPIP2ZAISHUNBOYOUDAODEAKIMOXINGZHONGDEZUOYONG,ZUZHIBINGLIXUEGAIBIANSHISHENZANGSUNSHANGDEZHIJIEZHIBIAO。ZHUSHECPHOUDI3TIAN,XIAOSHUPIMAOLINGLUAN,DONGZUOHUANMAN。CPZHILIAOHOU,XIAOSHUSHENZANGMINGXIANBIANBAI,CPCHULIZUXIAOSHUDEZUZHISUNSHANGMINGXIANGENGDA(TU1a,1b);WBSHIYANXIANSHI,CPZUDESHENZANGHEHK-2XIBAOZHONGSHENSUNSHANGFENZI-1(KIM-1)SHANGDIAO,PSTPIP2DANBAISHUIPINGXIAJIANG(TU1E,1F,1C,1D)。JIEGUOBIAOMINGPSTPIP2ZAISHUNBOCHULIDEXIAOSHUHEHK-2XIBAOZHONGDEBIAODAJIAODI。

 

TU1:ZAICPYOUDAODEAKIHEHK-2XIBAOZHONGPSTPIP2BIAODAXIADIAO。

 

XIBAODIAOWANGSHISHENDUXINGYAOWUYINQIDEAKIDEYIGEZHONGYAOTEZHENG。JIEGUOBIAOMINGYURONGMEIZUXIANGBI,ZAICPZHILIAOZUZHONGGUANCHADAOGENGDUODETUNELYANGXINGXIBAO,BINGXIANZHUSHANGDIAOLEXIBAODIAOWANGGUOCHENGZHONGQIHEXINZUOYONGDEcaspase-3QIEGEDANBAIDEBIAODA(TU2a,2b)。WEILETANTAOPSTPIP2DUICPYOUDAODEAKIDEKANGDIAOWANGZUOYONGJIZHI,CAIYONGLEXIANXIANGGUANBINGDU(AAV)JINXINGLETINEIDONGWUSHIYAN。YUCPCHULIZUXIANGBI,SHIYONGrAAV9–PSTPIP2KEXIANZHUJIANSHAOTUNELYANGXINGXIBAODESHULIANGBINGXIANZHUXIADIAOcaspase-3DANBAISHUIPING(TU2c,2d)。ZHEIXIEJIEGUOBIAOMINGPSTPIP2DUICPYOUDAODEAKIYOUBAOHUZUOYONG。

 

 

TU2:PSTPIP2YIZHICPYOUDAODESHENXIBAODIAOWANG。

CHABO:WENZHONGrAAV9–PSTPIP2-eGFPSHIYOUHANHENGSHENGWUTIGONGDEXIANXIANGGUANBINGDUBAOZHUANGXITONGJIEDAODE,WENZHONGTONGGUOWEIJINGMAIZHUSHEFANGSHIJIANGBINGDUZHUSHEJINRUXIAOSHUTINEI。

 

WEILEGENGHAODICHANMINGPSTPIP2DUISHENXIAOGUANSHANGPIXIBAOTEXINGDEYINGXIANG,ZUOZHETONGGUOFENBIEZAIJINGCPCHULIDEHK-2XIBAOZHONGZHUANRANPSTPIP2GUOBIAODAZHILI(pEX-2-PSTPIP2)HEPSTPIP2XIAOGANRAOXULIE(siRNA-PSTPIP2)YOUDAOPSTPIP2DEGUOBIAODAHECHENMO。LIUSHIFENXIXIANSHI,YUDUIZHAOZUXIANGBI,PSTPIP2DEGUOBIAODAHEQIAODIFENBIEXIANZHUJIANSHAOHEZENGDUOLEDIAOWANGXIBAODESHULIANG(TU3)。KEYITUIDUANPSTPIP2ZHUYAOTONGGUOYIZHIAKIZHONGHK-2XIBAODIAOWANGLAIFAHUIDIAOJIEZUOYONG。

 

 

TU3:PSTPIP2YIZHITIWAIPEIYANGDESHENXIAOGUANSHANGPIXIBAODIAOWANG。

CHABO:WENZHONGsiRNA-PSTPIP2SHIYOUHANHENGSHENGWUTIGONGDEXIAOGANRAORNA。

 

ZUIHOU,ZUOZHEYANJIULEPSTPIP2DUIBIAOGUANYICHUANDIAOKONGDEJIZHI。CPCHULIHOU,TONGGUORANSEZHIMIANYICHENDIAN(ChIP)JIANCEDAOPSTPIP2JIYINQIDONGZIQUDEZUDANBAIYIXIANHUAYOUSUOJIANGDI(TU4b)。WEILEJINYIBUTANSUOZUDANBAIXIUSHIZAIPSTPIP2DIAOKONGZHONGDEZUOYONG,BENWENTONGGUOWBFENXILEZUDANBAIYIXIANHUABIAOJI(H3K27Ac)DEBIAODAQINGKUANG。ZAICPCHULIDESHENZUZHIHECPCHULIDEHK-2XIBAOZHONG,H3K27AcDEDANBAISHUIPINGJIANGDI(TU4c,d)。RUTU4eSUOSHI,SUMUJING-YIHONG(H&E)RANSEXIANSHI,YUCPZUXIANGBI,ZUDANBAIQUYIXIANHUAMEI(HDAC)TEYIXINGYIZHIJI(TSA)CHULIHOUSHENXIAOGUANHUAISI、MEIJUNXINGCHENGHESHUAZHUANGYUANBAOLIUJIANSHAO。

 

 

TU4:HDACYIZHIJISHANGDIAOPSTPIP2ZAITINEIHETIWAIDEBIAODA。

 

BENYANJIUSHOUCIBIAOMINGHDACYIZHIJIKEYICUJINPSTPIP2DEBIAODA。PSTPIP2KEYIHUANJIESHUNBOZHILIAOHOUDESHENSUNSHANG,YUSHIPSTPIP2KEZUOWEIZHILIAOSHUNBOYOUDAODESHENDUXINGDEYOUXIAOZHILIAOCELVEDEYIBUFEN.

 

XIAMIANSHIXIAOHENGDEKEPUSHIJIAN:

 

化疗是化学药物治疗的简称,通过使用化学治疗药物杀灭癌细胞达到治疗目的。化疗是目前治疗癌症最有效的手段之一,和手术、放疗一起并称癌症的三大治疗手段。手术和放疗属于局部治疗,只对治疗部位的肿瘤有效,而化疗是一种全身治疗的手段,化疗药物会随着血液循环遍布全身的绝大部分器官和组织。因此,对一些有全身播撒倾向的肿瘤及已经转移的中晚期肿瘤,化疗都是主要的治疗手段。

化疗的效果确实如大多数人所言,会“敌我不分',杀死大量正常细胞,患者可能出现各种不同程度的副作用,甚至因不能耐受而被迫中止治疗。在各种传言当中,说的最严重的就是“化疗可能会加速患者的死亡,做了还不如不做”。这是一种很不负责任的说法。化疗确实存在不同程度的副作用,但是科学工作者也研究出了很多针对化疗副作用的药物去改善这种现象,所以我们要相信科学,相信科研工作者!

Chinese, Simplified