CN116808065B - lncRNA在治疗肥胖症中的应用 - Google Patents
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- CN116808065B CN116808065B CN202310818314.1A CN202310818314A CN116808065B CN 116808065 B CN116808065 B CN 116808065B CN 202310818314 A CN202310818314 A CN 202310818314A CN 116808065 B CN116808065 B CN 116808065B
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Abstract
本发明公开了lncRNA在治疗肥胖症中的应用,具体的,所述的lncRNA为Serpina4‑ps1。本发明记载了Serpina4‑ps1在生命早期高脂饮食暴露小鼠中显著上调。本发明同时记载了抑制Serpina4‑ps1的表达可以改善肝细胞脂代谢,提示Serpina4‑ps1可应用于肥胖症的诊断和治疗。本发明为肥胖症的诊断和治疗提供了新的途径。
Description
技术领域
本发明属于生物医药领域,具体涉及lncRNA在治疗肥胖症中的应用。
背景技术
肥胖是由能量摄入和能量消耗长期失衡引起的脂肪过度堆积。近年来,我国超重率及肥胖症发病率不断攀升。肥胖症已成为主要的公共健康问题。肥胖增加糖尿病、脂肪肝、心血管疾病、癌症等多种疾病的风险,导致患者生活质量及寿命下降,严重威胁人类健康。新近研究发现生命早期环境对成年期慢性病的发生具有重要驱动作用。针对生命早期不良环境进行尽早干预是及其重要的。肥胖症的早期防治具有重要价值。多项大型流行病学研究显示,早期预防及早期干预可延缓脂代谢紊乱发生,改善心血管并发症预后。
长链非编码RNA(lncRNA)广泛存在于人类基因组内,长度超过200个核苷酸,常定位于细胞浆内或细胞核内,本身缺乏开放阅读框(ORF),不具备翻译成蛋白质的能力。随着基因组测序的发展,科学家发现lncRNA在转录及转录后水平,调控真核生物基因表达。长链非编码RNA与脂代谢的也存在密切关系。因此,研究lncRNA与生命早期不良环境导致的脂代谢紊乱的相关性,寻找与肥胖发生发展相关的lncRNA标志物,对揭示肥胖的发病机制,实现肥胖早期防控具有重要意义。
目前对肥胖症的治疗主要包括饮食和生活方式干预、减肥手术及药物治疗。治疗策略主要是增加机体能量消耗或减少机体能量摄入,以实现机体能量稳态的负平衡,减少能量堆积。但临床上采用的减肥手术或减肥药物通常具有一定的副作用,对身体造成健康风险。减肥手术存在一定的外科风险,也可能影响到中枢前额叶皮层和多巴胺能信号通路,可能会提高机体对其他奖励如酒精的敏感性。因此,探索肥胖症潜在的分子机制和新的治疗靶点,对肥胖症治疗具有重要意义。
发明内容
为解决现有技术的不足,本发明的目的是提供一种肥胖症的标志物,可以实现肥胖症的诊断和治疗。
为了实现上述目的,本发明采用了如下技术方案:
第一方面,本发明提供了一种预防或治疗肥胖症、过度脂肪累积、和/或与前两者中任一种相关的代谢紊乱的药物组合物,所述的药物组合物包括lncRNA的抑制剂,所述的lncRNA为Serpina4-ps1。
如本文所用,术语“lncRNA”、“长链非编码RNA”、“Long non-coding RNA”含义相同,互换使用,都是指一种由RNA聚合酶II转录、不编码蛋白的、一般长度大于200bp的RNA片段。
本发明中,所述的Serpina4-ps1是GenBank ID为NR_002861的lncRNA。
进一步,所述的抑制剂包括shRNA、siRNA、dsRNA或反义核酸。
进一步,所述的抑制剂为siRNA。
进一步,所述的siRNA的序列如SEQ ID NO.3所示。
本发明的药物组合物特征为至少是无菌且不含热原的。在制备这些药物组合物时,通常将活性成分与赋形剂混合,或用赋形剂稀释,或包在可以以胶囊或药囊形式存在的载体中。当赋形剂起稀释剂作用时,它可以是固体、半固体或液体材料作为赋形剂、载体或活性成分的介质。因此,组合物可以是片剂、丸剂、粉剂、溶液剂、糖浆剂、灭菌注射溶液等。合适的赋形剂的例子包括:乳糖、葡萄糖、蔗糖、山梨醇、甘露醇、淀粉、微晶纤维素、聚乙烯吡咯烷酮、纤维素、水等。制剂还可包括:湿润剂、乳化剂、防腐剂(如羟基苯甲酸甲酯和丙酯)、甜味剂等。
该药物组合物的应用为肥胖症、过度脂肪累积、和/或与前两者中任一种相关的代谢紊乱的治疗提供了一种方法,具体为一种预防或治疗肥胖症、过度脂肪累积、和/或与前两者中任一种相关的代谢紊乱的方法,包括将有效剂量的所述的药物组合物施用于对象中。所述药物组合物用于预防或治疗肥胖症、过度脂肪累积、和/或与前两者中任一种相关的代谢紊乱时,需要将有效剂量的所述的药物组合物施用于受试者中。
第二方面,本发明提供了如下任一项应用:
(1)本发明第一方面所述的药物组合物在制备预防或治疗肥胖症、过度脂肪累积、和/或与前两者中任一种相关的代谢紊乱的药物中的应用;
(2)本发明第一方面所述的药物组合物在制备改善肝细胞脂代谢的药物中的应用。
第三方面,本发明提供了一种筛选预防或治疗肥胖症、过度脂肪累积、和/或与前两者中任一种相关的代谢紊乱的候选药物的方法,所述的步骤包括:
用待筛选物质处理含有Serpina4-ps1的体系,和
检测所述体系中Serpina4-ps1表达,
其中,若候选物质可降低Serpina4-ps1的表达,则表明该候选物质是预防或治疗肥胖症、过度脂肪累积、和/或与前两者中任一种相关的代谢紊乱的候选药物。
所述候选物质包括(但不限于):针对Serpina4-ps1序列或其上游或下游序列设计的抑制Serpina4-ps1表达的试剂、结合分子、小分子化合物等。
所述体系选自:细胞体系、亚细胞体系、溶液体系、组织体系、器官体系或动物体系。
其中,若所述候选物质可下调Serpina4-ps1的表达水平(优选显著下调,如下调20%以上,较佳的下调50%以上,更佳的下调80%以上),则表明该候选物质是预防或治疗肥胖症、过度脂肪累积、和/或与前两者中任一种相关的代谢紊乱的潜在物质。
第四方面,本发明提供了一种非治疗目的的抑制肝细胞中甘油三酯的生成的方法,所述的方法包括向肝细胞施用lncRNA的抑制剂,所述的lncRNA为Serpina4-ps1。
进一步,所述的抑制剂包括shRNA、siRNA、dsRNA或反义核酸。
进一步,所述的抑制剂为siRNA。
进一步,所述的siRNA的序列如SEQ ID NO.3所示。
第五方面,本发明提供了检测生物样品中lncRNA的表达水平的试剂在制备诊断肥胖症、过度脂肪累积、和/或与前两者中任一种相关的代谢紊乱的产品中的应用,所述的lncRNA包括Serpina4-ps1。
进一步,所述的肥胖症为生命早期高脂饮食暴露引发的肥胖症。
进一步,所述的过度脂肪累积为生命早期高脂饮食暴露引发的过度脂肪累积。
进一步,所述的试剂包括通过RT-PCR、qPCR、原位杂交或高通量测序平台检测生物样品中lncRNA的表达水平的试剂。
进一步,所述的生物样品为肝脏组织。
进一步,所述的产品包括试剂盒、芯片、核酸膜条。
“芯片”包括基因芯片;所述基因芯片包括固相载体;以及有序固定在所述固相载体上的寡核苷酸探针,所述的寡核苷酸探针特异性地对应于Serpina4-ps1所示的部分或全部序列。所述固相载体包括无机载体和有机载体,所述无机载体包括但不限于有硅载体、玻璃载体、陶瓷载体等;所述有机载体包括聚丙烯薄膜、尼龙膜等。
“试剂盒”可用于检测Serpina4-ps1的表达水平,包含用于Serpina4-ps1检测和/或定量的引物、寡核苷酸探针和/或芯片。试剂盒还可以包括选自下组的一种或多种物质:容器、使用说明书、阳性对照物、阴性对照物、缓冲剂、助剂或溶剂。
本发明的试剂盒中还可附有试剂盒的使用说明书,其中记载了如何采用试剂盒进行检测,和如何利用检测结果对疾病发展进行判断、对治疗方案进行选择。
试剂盒的组分可以以水介质的形式或以冻干的形式来包装。试剂盒中适当的容器通常至少包括一种小瓶、试管、长颈瓶、宝特瓶、针筒或其它容器,其中可放置一种组分,并且优选地,可进行适当地等分。在试剂盒中存在多于一种的组分时,试剂盒中通常也将包含第二、第三或其它附加的容器,其中分离地放置附加的组分。然而,不同组合的组分可被包含在一个小瓶中。本发明的试剂盒通常也将包括一种用于容纳反应物的容器,密封以用于商业销售。这种容器可包括注模或吹模的塑料容器,其中可保留所需的小瓶。
“核酸膜条”包括基底和固定于所述基底上的特异性识别Serpina4-ps1的探针;所述基底可以是任何适于固定探针的基底,例如尼龙膜、硝酸纤维素膜、聚丙烯膜、玻璃片、硅胶晶片、微缩磁珠等。
进一步,所述的试剂选自:
特异性识别Serpina4-ps1的探针;
或特异性扩增Serpina4-ps1的引物;
进一步,所述的引物的序列如SEQ ID NO.1-2所示。
除非另有定义,本发明上下文中的所有科技术语具有本领域普通技术人员所理解的相同含义。此外,对部分术语解释如下。
本文中使用的术语“标志物”指代具有特异性生物学特性、生物化学特征或者方面的分子指示物,其可用于确定存在或不存在特定疾病或状况和/或特定疾病或状况的严重程度。其和“生物标志物”、“基因标志物”可以通用。
术语“shRNA”是指具有茎-环结构的RNA药剂,所述茎-环结构包括互补序列的第一区域和第二区域,区域的互补性和取向程度足以使得区域之间发生碱基配对,第一区域和第二区域通过环区域接合,所述环是由于环区域内的核苷酸(或核苷酸类似物)之间缺乏碱基配对而产生的。环中核苷酸的数量是介于3到23、或5到15、或7到13、或4到9、或9到11之间并且包含其的数字。环中核苷酸的有一些可以参与到与环中的其它核苷酸的碱基对相互作用中。
术语“siRNA”是指诱导RNA干扰(RNAi)路径的抑制性小RNA双螺旋(一般在18-30个碱基对之间,在19到25个碱基对之间)。通常,化学合成呈21聚体(21mer)的siRNA,其具有19bp的中心双螺旋区和在末端的对称的2碱基3'突出端,但是最近已描述了与相同位置处的21聚体相比,25-30碱基长度的化学合成的RNA双螺旋可以在效价上有多达100倍的提高。
本文中使用的术语“dsRNA”指包含相互互补序列的两个RNA分子的构建体,所述两个RNA分子通过所述互补序列退火以形成双链RNA分子。
术语“生物样品”是指来自个体或(对照)受试者的包含本发明生物标志物的任何生物样品。生物样品可以是体液样品或组织样品。例如,本发明涵盖的生物样品是组织样品、血液(例如全血或血液组分,例如血细胞/细胞组分、血清或血浆)样品、尿液样品、脑脊液(CSF)或来自其它外周来源的样品。所述生物样品可以混合或合并,例如,样品可以是血液样品和尿液样品的混合物。所述生物样品可以通过从个体或(对照)受试者中取出生物样品来提供,但也可以通过使用先前分离的样品来提供。例如,可以通过常规血液采集技术从个体或(对照)受试者获取血液样品,或者可以通过活组织检查(biopsy)从个体或(对照)受试者获取组织样品。生物样品(例如尿液样品、血液样品或组织样品)可以在治疗性治疗开始之前、治疗性治疗期间和/或治疗性治疗之后从个体或(对照)受试者获得。如果生物样品是从至少一个(对照)受试者获得的,例如从至少1、2、3、4、5、6、7、8、9、10、20、30、40、50、60、70、80、90、100、150、200、250、300、400、500或1,000个(对照)受试者获得,则将其指定为“参比生物样品”。优选地,参比生物样品来自与待测试个体的生物样品相同的来源,例如,两者都是血液样品、尿液样品或组织样品。进一步优选两者来自相同的物种,例如来自人。(替代地或额外地)还优选(对照)受试者的参比生物样品和待测试个体的生物样品的度量是相同的,例如,两者具有相同的体积。特别优选参比生物样品和生物样品来自相同性别和相似年龄的(对照)受试者/个体。
所述体液样品可以是尿液样品、血液样品、痰样品、母乳样品、脑脊液(CSF)样品、耵聍(耳垢)样品、胃液样品、粘液样品、内淋巴液样品、外淋巴液样品、腹膜液样品、胸膜液样品、唾液样品、皮脂(皮肤油脂)样品、精液样品、汗液样品、泪液样品、面颊拭子、阴道分泌物样品、液体活检或呕吐物样品,包括它们的成分(components)或组分(fractions)。术语“体液样品”还涵盖体液组分,例如血液组分、尿液组分或痰组分。体液样品可以混合或合并。因此,体液样品可以是血液和尿液样品的混合物,或者血液和脑脊液样品的混合物。
本文所用的术语“引物”指能够与靶标核酸发生结合的单链寡核苷酸。通常,结合是选择性结合。引物的精确长度会随特定的应用而异,但通常为约15至约120个核苷酸。引物不需要反映靶标核酸模板的确切序列,但必须有足够的互补性以与模板发生结合。供用作引物的寡核苷酸可用本领域已知用于该用途的软件来选择。例如,OLIGO4.06引物分析软件(可获自National Biosciences,Plymouth,MN)可用于选择各自最长达30-100个核苷酸的引物,和用于从最长达32千碱基的输入多核苷酸序列中分析最长达5,000个核苷酸的更大多核苷酸。类似的引物选择程序已并入了额外的特征以扩展性能。例如,PrimOU引物选择程序(公众可从University of Texas South WestMedical Center(位于Dallas TX)的Genome Center获得)能够从兆碱基序列中选择特异的引物,因此可用于在基因组范围内设计引物。Primer3引物选择程序(公众可从WhiteheadInstitute/MITCenter for Genome5Research,Cambridge MA获得)能让使用者输入“mispriminglibrary”,其中要避免作为引物结合位点的序列是使用者指定的。Primer3对于选择微阵列用核苷酸特别有用。(后两个引物选择程序的源代码也可从它们各自的来源获得,并作修改以符合使用者的具体需要)。PrimeGen程序(公众可从UK Human GenomeMappingProjectResource Centre,CambridgeUK获得)基于多个序列比对来设计引物,从而使得可以选择出能与所比对的核酸序列的最保守区域或最不保守区域结合或杂交的引物。因此,这个程序可用于鉴定独特和保守核苷酸以及多核苷酸片段。
术语“探针”是指可与试样中的所要检测的靶物质特异性结合的物质,是指可通过上述结合特异性确认试样中的靶物质的存在的物质。探针的种类为本领域通常使用的物质,并无限制,优选地,可以为肽核酸(PNA,peptide nucleic acid)、锁核酸(LNA,lockednucleic acid)、肽、多肽、蛋白质、核糖核酸或脱氧核糖核酸。
本发明的优点和有益效果:
本发明首次发现了Serpina4-ps1在生命早期高脂饮食暴露小鼠中差异表达,进一步通过细胞实验发现,Serpina4-ps1的抑制剂可以改善肝细胞脂代谢,提示Serpina4-ps1的抑制剂可应用于肥胖症的诊断和治疗。本发明为肥胖症治疗提供了新方法,为寻找肥胖症的标志物提供了科学依据。
附图说明
图1为检测母代高脂饮食对子代小鼠的影响的结果图,其中,图A为检测母代高脂(HFD)饮食对子代小鼠8周龄体重的影响的结果图,图B为检测母代高脂饮食对子代小鼠8周龄皮下脂肪含量(SAT)的影响的结果图,图C为检测母代高脂饮食对子代小鼠8周龄内脏脂肪含量(VAT)的影响的结果图,图D为检测母代高脂饮食对子代小鼠8周龄肝脏lncRNASerpina4-ps1表达的结果图,图中**表示P<0.01,SD表示对照饲料组,HFD表示高脂饲料组;
图2为证明lncRNA Serpina4-ps1小干扰RNA转染改善肝细胞棕榈酸(PA)诱导的甘油三酯生成的结果图,其中,图A为lncRNA Serpina4-ps1小干扰RNA(siRNA)转染后肝细胞lncRNA Serpina4-ps1相对表达的结果图,图B为棕榈酸干预及lncRNA Serpina4-ps1小干扰RNA转染对小鼠原代肝细胞甘油三酯含量的影响的结果图,图中**表示P<0.01与对照组(control)比较;##表示P<0.01与棕榈酸(PA)处理组比较。
具体实施方式
为了对本发明的技术特征、目的和有益效果有更加清楚的理解,现结合具体实施例对本发明的技术方案进行以下详细说明,应理解这些实例仅用于说明本发明而不用于限制本发明的范围。实施例中,各原始试剂材料均可商购获得,未注明具体条件的实验方法为所属领域熟知的常规方法和常规条件,或按照仪器制造商所建议的条件。
实施例1生命早期高脂饮食暴露小鼠肝脏lncRNA Serpina4-ps1表达显著升高
一、实验材料
C57BL/6J小鼠(北京华阜康生物科技有限公司)
正常啮齿类饲料(北京华阜康生物科技有限公司)
高脂饲料(北京华阜康生物科技有限公司)
TRIzol试剂(Sigma)
氯仿(上海化学试剂有限公司)
异丙醇(上海化学试剂有限公司)
逆转录试剂盒(TaKaRa)
SybrGreen实时定量PCR试剂盒(ABI)
ViiaA7实时定量PCR系统(ABI)
lncRNA Serpina4-ps1实时定量PCR引物见表1。
表1 lncRNA Serpina4实时定量PCR引物
二、实验方法
购买5周龄C57BL/6J小鼠(北京华阜康生物科技有限公司,雌性16只,雄性8只)。雌鼠随机分为正常饮食组(SD,n=8)和高脂饮食组(HFD,n=8)。正常饮食组给予正常啮齿类饲料(北京华阜康生物科技有限公司),饲料能量比为脂肪10%、蛋白质20%、碳水化合物70%。高脂饮食组给予高脂饲料(北京华阜康生物科技有限公司),饲料能量比为脂肪45%、蛋白质20%、碳水化合物35%。自由饮食、摄食。3周后,雌鼠与雄鼠(给予正常饲料)以2:1的数量合笼。以见阴栓为妊娠第一天。孕鼠在孕期和哺乳期继续给予正常饲料或高脂饲料。子代小鼠8周龄时,称量体重。随后,处死小鼠,取性腺周围内脏脂肪和腹股沟皮下脂肪称重。取肝脏。
大约50mg肝脏,加入1mL TRIzol试剂,匀浆。匀浆后,室温静置5min。随后加入0.2mL氯仿。室温孵育3min。4℃12000g离心15min。离心后,将最上层上清液转移至无RNA酶ep管。加入0.5mL异丙醇,混匀后,室温孵育10min,4℃12000g离心10min。弃去上清,得到RNA沉淀。采用逆转录试剂盒(TaKaRa)进行逆转录。得到cDNA,配置实时定量PCR反应体系。在实时定量PCR仪上运行以下程序:95℃,10min;40个PCR循环(95℃,10sec;60℃,60sec(收集荧光))。为了建立PCR产物的熔解曲线,扩增反应结束后,按(95℃,10sec;60℃,60sec;95℃,15sec);并从60℃缓慢加热到99℃。以Actin为内参,使用实时定量PCR法检测lncRNASerpina4-ps1表达,2-△△Ct法进行相对定量。
三、实验结果
如图1所示,生命早期高脂饮食暴露小鼠体重显著升高(P<0.01),皮下脂肪(SAT)和内脏脂肪(VAT)含量显著增加(均P<0.01)。生命早期高脂饮食暴露小鼠肝脏lncRNASerpina4-ps1表达显著升高(P<0.01)。
实施例2 lncRNA Serpina4-ps1 siRNA改善肝细胞脂代谢
一、实验材料
细胞孵箱(Thermo)
C57BL/6J小鼠(北京华阜康生物科技有限公司)
DMEM培养基(Gibco)
胎牛血清(Gibco)
棕榈酸(Sigma)
Lipofectamine RNAiMAX转染试剂盒(Thermo Fisher公司)
甘油三酯检测试剂盒(北京索莱宝科技公司)
BCA蛋白试剂盒(江苏凯基生物技术股份有限公司)
二、实验方法
从C57BL/6J小鼠肝脏分离原代肝细胞。分离的小鼠原代肝细胞使用DMEM培养基,37℃,5%CO2孵箱培养。根据lncRNA Serpina4-ps1序列,设计lncRNA Serpina4ps1 siRNA,合成siRNA(广州锐博公司)。转染前24h接种约1x106个/孔肝细胞于六孔板中,在细胞密度达到70%时,将培养基换成无血清培养基。将稀释好的siRNA与Lipofectamine RNAiMAX转染试剂混合,轻柔混匀,室温孵育20min,形成转染复合物。然后,将上述混合物加入细胞培养基中,轻轻混匀,在5%CO2、37℃培养箱中培养,6h后更换完全培养基。16h后加入棕榈酸(1mmol/L)处理肝细胞。
细胞处理24h后,吸取培养基,PBS洗1次,用胰酶消化制备细胞悬液,1000r/min,离心10min,弃去上清,再用PBS洗2次,1000r/min,离心10min,弃去上清液,保留细胞沉淀。用2%Triton-100裂解30min,裂解后按照甘油三酯试剂盒说明,在420nm处,酶标仪测定各孔OD值,每个样本3个复孔。并用BCA法测定每孔细胞蛋白含量。TG含量表示为mmol/g蛋白。
细胞处理24h后,吸取培养基,PBS洗2次。每孔加入1mL TRIzol试剂,反复吹打混匀,使细胞充分裂解,室温静置10min。将裂解液转移到ep管中,加入0.2mL氯仿。室温孵育3min。4℃12000g离心15min。离心后,将最上层上清液转移至无RNA酶ep管。加入0.5mL异丙醇,混匀后,室温孵育10min,4℃12000g离心10min。弃去上清,得到RNA沉淀。采用逆转录试剂盒(TaKaRa)进行逆转录。得到cDNA,配置实时定量PCR反应体系。在实时定量PCR仪上运行以下程序:95℃,10min;40个PCR循环(95℃,10sec;60℃,60sec(收集荧光))。为了建立PCR产物的熔解曲线,扩增反应结束后,按(95℃,10sec;60℃,60sec;95℃,15sec);并从60℃缓慢加热到99℃。以Actin为内参,使用实时定量PCR法检测lncRNA Serpina4-ps1表达,2-△△Ct法进行相对定量。
表2 lncRNA Serpina4-ps1小干扰RNA(siRNA)序列
siRNA名称 | 序列 | SEQ ID NO. |
si-m-Serpina4-ps1_001 | CCACCGAAACCTCCTTTAA | 3 |
三、实验结果
如图2所示,小鼠原代肝细胞转染lncRNA Serpina4-ps1小干扰RNA后,lncRNASerpina4-ps1水平显著降低(P<0.01)。转染lncRNA Serpina4-ps1小干扰RNA入小鼠原代肝细胞,改善棕榈酸诱导的甘油三酯生成(P<0.01)。可见,lncRNA Serpina4-ps1小干扰RNA能改善肝细胞脂代谢。
需要说明的是:以上实施例仅用于说明本发明的实施过程和特点,而非限制本发明的技术方案,尽管参照上述实施例对本发明进行了详细说明,本领域的普通技术人员应当理解:依然可以对本发明进行修改或者等同替换,而不脱离本发明的精神和范围的任何修改或局部替换,均应涵盖在本发明的保护范围当中。
Claims (4)
1.药物组合物在制备预防或治疗肥胖症、过度脂肪累积、和/或与前两者中任一种相关的代谢紊乱的药物中的应用;所述药物组合物包括lncRNA Serpina4-ps1的抑制剂,所述的抑制剂包括siRNA;所述siRNA的序列如SEQ ID NO.3所示。
2.根据权利要求1所述的应用,其特征在于,所述的药物组合物还包括药学上可接受的载体。
3.根据权利要求2所述的应用,其特征在于,所述的药学上可接受的载体包括溶剂、分散剂、悬浮助剂、表面活性剂、等渗剂、增稠剂、防腐剂、固体粘合剂、润滑剂。
4.一种非治疗目的的抑制肝细胞中甘油三酯的生成的方法,其特征在于,所述的方法包括向肝细胞施用lncRNA的抑制剂,所述的lncRNA为Serpina4-ps1,所述的抑制剂包括siRNA,所述的siRNA的序列如SEQ ID NO.3所示。
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