CN102188441A - 微小分子rna-155的抗动脉粥样硬化药物用途 - Google Patents
微小分子rna-155的抗动脉粥样硬化药物用途 Download PDFInfo
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Abstract
本发明提供一种miRNA-155在制备抗动脉粥样硬化炎症药物中的应用。本发明通过实验证明，无论在体外细胞水平还是体内动脉粥样模型小鼠水平，都证实了miRNA-155对动脉粥样硬化炎症具有明显的抑制作用，由于miRNA-155是位于基因上游的调控分子，并且同时有多种生物学功能，因此miRNA-155很有可能成为动脉粥样硬化治疗的全新靶点。本发明的药物能有效的防治核酸在生物体内降解，并能高效的作用目的组织，所述药物还可以与目前已知的其他治疗动脉粥样硬化炎症的药物如他汀类调脂药等制成复方制剂。
Description
技术领域
本发明属于生物技术领域，涉及微小分子RNA-155在制备抗动脉粥样硬化药物中的用途。
背景技术
目前一致公认动脉粥样硬化（atherosclerosis, AS）是多基因，多因素的疾病，其发病机制与炎症反应，氧化应激，细胞凋亡以及血流动力学改变等有关，是一个极为复杂的病理过程。AS斑块的不稳定将导致严重心血管事件，免疫炎症反应在AS发生尤其是斑块的稳定性中起着关键作用。斑块不稳定也受多因素的影响，某一种蛋白或者分子异常往往无法反映整个病理过程，以往单纯针对某个靶基因/蛋白或者某个转导通路进行干预的传统方法存在很大局限性，因此了解AS免疫细胞生物学功能的多靶位基因表达机制，将是我们更深入认识AS形成的病理生理机制、寻找调控AS靶点的关键，microRNA的出现为这一目标的实现提供了极大的可能。
MicroRNAs(miRNAs)是一组长约22个核苷酸、保守的非编码小RNA，通过转录后水平调控基因的表达从而在生物过程中发挥重要的作用。MiRNA表达水平的改变能够调节许多心血管疾病发生相关的重要生物学过程，如心脏发育，心肌肥厚，心律失常，血管发生等，系统评价某种确定表型AS 相关miRNA表达谱的变化将有利于我们更深入的理解AS发生发展和转归的机制。miRNA-155是近几年来发现在免疫炎症中有重要调控作用的经典microRNA，并有许多研究证实了其与免疫炎症相关的靶基因。
现阶段，针对动脉粥样硬化、冠心病的预防和治疗主要集中在抑制动脉粥样硬化炎症反应、调整血脂、抑制血小板聚集、去除/减少致动脉粥样硬化进展的多种危险因素等措施，根据发明人对本领域的研究和检索，目前microRNA对动脉粥样硬化治疗方面的研究几乎近于空白。因而，根据microRNA的作用机制提示进行一系列研究来明确miRNA-155在改善动脉粥样硬化炎症反应，实现对冠心病的防治很有必要，并期待通过本发明人的一系列验证使miRNA-155有望成为一种改善动脉粥样硬化、治疗冠心病的新型核酸药物。
发明内容
本发明的目的在于提供一种微小分子RNA-155（miRNA-155）在制备抗动脉粥样硬化炎症药物中的应用，所述miRNA-155的核苷酸序列如SEQ ID NO:1所示：UUAAUGCUAAUCGUGAUAGGGGU。
本发明所述的miRNA-155作为原料药用于制备预防和治疗动脉粥样硬化炎症的核酸药物，该药物能有效的防治核酸在生物体内降解，并能高效的作用目的组织，本发明所述的miRNA-155还可以与目前已知的其他治疗动脉粥样硬化炎症的药物，如他汀类调脂药等制成复方制剂，用于治疗动脉粥样硬化炎症。
本发明通过各种实验证明，无论在体外细胞水平还是体内动脉粥样模型小鼠水平，都证实了miRNA-155对动脉粥样硬化炎症具有明显的抑制作用，由于miRNA-155 是位于基因上游的调控分子，并且同时有多种生物学功能，因此miRNA-155很有可能成为动脉粥样硬化治疗的全新靶点。本发明开辟了miRNA-155作为一种核酸药物的新用途，也为动脉粥样硬化炎症的治疗提供了一种新的途径。
附图说明
图1 miRNA-155 对THP-1细胞MAPK信号通路（p38, JNK, ERK1/2）作用。
图2 miRNA-155体内激动剂agomir-155对APOE动脉粥样硬化模型小鼠血清，血管以及外周血单个核细胞炎症因子TNF-a蛋白水平影响。
图3是miRNA-155体内激动剂agomir-155对APOE动脉粥样硬化模型小鼠血清，血管以及外周血单核细胞炎症因子IL-6蛋白水平影响。
图4 miRNA-155体内激动剂agomir-155对APOE动脉粥样硬化模型小鼠血清，血管以及外周血单个核细胞炎症因子TNF-a分子水平影响。
图5是miRNA-155体内激动剂agomir-155对APOE动脉粥样硬化模型小鼠血清，血管以及外周血单核细胞炎症因子IL-6分子水平影响。
具体实施方式
本发明结合附图和实施例作进一步的说明。
实施例1 miR-155转染THP-1细胞后细胞生物学功能变化
本申请用于体外细胞实验转染用的miRNA-155（SEQ ID NO:2）模拟物/抑制剂均购买于美国ABI公司，用于体内动物实验的agomir-155（SEQ ID NO:3）购买于广州锐博生物技术有限公司，均为商业化产品。
1、miR-155模拟物/抑制剂转染后，用oxLDL刺激48小时，Real-time PCR及Northern blot检测各组细胞相应miR-155表达改变的效果，
分组如下：空白对照组、单独oxLDL刺激组、转染模拟物阴性对照组，转染抑制剂阴性对照组，转染miR-155模拟物组，转染miR-155抑制剂组；
2、ELISA检测炎症因子变化TNF-α、Il-6分泌（表1）
表1 miRNA-155 对THP-1细胞炎症因子分泌影响
| IL-6(ng/ml) | TNF-α(ng/L) | |
| 空白对照 | 1.04±0.06 | 70.6±5.06 |
| 模拟物对照 | 0.93±0.52 | 75.3±4.06 |
| miR-155模拟物 | 0.56±0.04** | 34.34±1.32** |
| 抑制剂对照 | 0.96±0.05 | 74.06±0.88 |
| miR-155抑制剂 | 1.68±0.12## | 110.51±3.58## |
3、检测MAPK信号转导通路的改变：实验分组（同上）。Westernblot检测炎症通路中信号分子P38,JNK,ERK蛋白水平（参见图1）。
实施例2 miR -155在动脉粥样硬化模型动物水平治疗潜力研究
1 、实验动物（雄性ApoE-/-小鼠，12周龄）的分组及agomir/antagomir-155干预
1.1 胆固醇修饰的agomir/antagomir-155转染效率的筛选：
1)鉴定agomir/antagomir-155体外对细胞的转染效率
将Cy3标记的胆固醇修饰的而RNA类似参照物与DC细胞共培养，设置浓度梯度为100nmol，200nmol和400nmol，荧光显微镜观察胆固醇修饰的miRNA阴性对照在没有转染辅助试剂的情况下的入胞效率；
2)鉴定agomir/antagomir在体对目的组织的转染效率
将Cy5标记的胆固醇修饰的而RNA类似参照物用纳米脂质体包裹，设置注射剂量为2.5nmol，5nmol，10nmol，15nmol，隔天注射，一周后做目的血管免疫组化切片，荧光显微镜观察胆固醇修饰miRNA阴性对照转染效率，筛选出转染效率最高的浓度组。
1.2 agomir -155静脉注射ApoE小鼠体内：
实验分组：
空白对照组：注射PBS，
阴性对照组：注射agomir-neg，
Agomir处理组：注射Agomir最佳浓度 ，隔天注射，连续一周。
2、AS病理进程及相关全身炎症指标检测：一周后处死小鼠，常规取材，行斑块面积（稳定斑块和不稳定斑块），纤维帽厚度检测，脂质核心面积大小测量。同时按照常规生化检测要求取血并准备各组小鼠血浆样本，应用全自动生化分析仪测定血脂等相关指标检测。
3、斑块局部指标检测：小鼠干预1周后，取心脏到主动脉根部标本，取2－3cm，进行石蜡切片，切片进行苏木精染色和免疫组化研究，测定斑块局部炎症因子VCAM1, ICAM1, IL-10, 1L-6, TNF-a, MCP1,斑块平滑肌含量指标SMC α-actin、免疫炎症细胞浸润指标CD3，CD4,CD68，MAC-2分泌，显微镜下拍照留样，图片经Image Pro Plus 图像分析软件分析结果。
4、小鼠炎症因子变化：药物治疗一周后，荧光定量PCR分别观察小鼠血管组织，血浆和骨髓来源的单个核细胞炎症因子TNF-a和IL-6的变化（参见图2,3），同时用ELISA试剂盒检测其相应的蛋白水平变化（参见图4,5）。
实施例3 生物信息学预测，基因表达谱筛选miR -155炎症相关的作用靶点，证明其在细胞内对应的mRNA靶序列，并探讨其作用机制。
1、 根据miR-155靶点预测数据库及其法则，推测出相应miRNA可能的mRNA靶序列。
2、用特异miR-155模拟物/抑制剂作用细胞，进行基因表达谱芯片筛选其改变的mRNA：
实验分组：空白对照组，miR-155 模拟物处理组，miR-155抑制剂处理组；转染细胞24-48小时后，提取RNA，用mRNA表达谱芯片筛选经过miRNA作用后细胞mRNA水平发生的变化。
3、结合生物信息学数据和表达谱芯片数据以及AS免疫炎症反应病理过程，挑选出最有可能是miR-155靶基因的mRNA-- MAP3K10。
4、构建miR-155的靶mRNA --MAP3K10的3’端非翻译区(3’-UTR)的荧光报告载体：MAP3K10 的3’-UTR片段被克隆入含有萤火虫荧光素酶表达的pMIR-REPORT vector (Ambion)，记为CMV-靶mRNA-UTR。根据荧光素的表达来判定其靶mRNA的表达强弱。
5、将miR-155模拟物/抑制剂和荧光报告载体CMV-靶mRNA-UTR共转染293T细胞，观察细胞荧光表达来判定miR-155相应的mRNA靶序列。
<110> 浙江大学
<120> 微小分子RNA-155的抗动脉粥样硬化药物用途
<160> 3
<210> 1
<211> 23
<212> RNA
<213> 人（homo sapiens. hsa）
<222> miRbase 数据库上公开的miR-155序列
<400> 1
uuaaugcuaaucgugauaggggu
<210> 2
<211> 46
<212> RNA
<213> 人（homo sapiens. hsa）
<222> 末端加上dTdT悬垂,全部碱基甲基化修饰
<400> 2
dtdtaauuacgauuagcacuaucccca uuaaugcuaaucgugauaggggudtdt
<210> 3
<211> 23
<212> RNA
<213> 人（homo sapiens. hsa）
<222> 末端加上dTdT悬垂,全部碱基甲基化修饰
<400> 3
dtdtaauuacgauuagcacuaucccca
Claims (4)
1.一种微小分子RNA-155在制备抗动脉粥样硬化炎症药物中的应用，所述miRNA-155的核苷酸序列如SEQ ID NO:1所示：UUAAUGCUAAUCGUGAUAGGGGU。
2.根据权利要求1所述的一种微小分子RNA-155在制备抗动脉粥样硬化炎症药物中的应用，其特征在于，所制备的药物还含有其他治疗动脉粥样硬化炎症的药物。
3.根据权利要求1或2所述的一种微小分子RNA-155在制备抗动脉粥样硬化炎症药物中的应用，其特征在于，所述药物的制剂形式为液体制剂、颗粒剂、片剂或胶丸。
4.根据权利要求3所述的一种微小分子RNA-155在制备抗动脉粥样硬化炎症药物中的应用，其特征在于，所述药物的给药方式包括口服给药或注射给药。
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102766594A (zh) * | 2012-06-01 | 2012-11-07 | 中国人民解放军第二军医大学 | 一种应用miRNA抑制内皮细胞迁移的方法 |
| CN105251008A (zh) * | 2015-10-26 | 2016-01-20 | 上海交通大学医学院附属仁济医院 | MicroRNA-155拮抗剂在制备治疗硬皮病的药物中的应用 |
| CN112941074A (zh) * | 2021-01-20 | 2021-06-11 | 青岛大学附属医院 | MicroRNA-302c-3p作为NLRP3抑制剂的应用 |
-
2011
- 2011-05-09 CN CN 201110118513 patent/CN102188441A/zh active Pending
Non-Patent Citations (4)
| Title |
|---|
| 《Chin J Arterioscler,》 2010 杨蕾等 MicroRNA和动脉粥样硬化的关系 916-918 1-4 第18卷, 第11期 * |
| 《FEBS Letters》 2010 Bin Tang, et al Identification of MyD88 as a novel target of miR-155, involved in negative regulation of Helicobacter pylori-induced inflammation 1481-1486 1-4 第584卷, * |
| 《PNAS》 20070130 Ryan M. O'Connell， et al. MicroRNA-155 is induced during the macrophage inflammatory response 1604-1609 1-4 第104卷, 第5期 * |
| 《中国动脉硬化杂志》 2010 陈妍梅等 microRNA与动脉粥样硬化炎症反应 662-664 1-4 第18卷, 第8期 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102766594A (zh) * | 2012-06-01 | 2012-11-07 | 中国人民解放军第二军医大学 | 一种应用miRNA抑制内皮细胞迁移的方法 |
| CN105251008A (zh) * | 2015-10-26 | 2016-01-20 | 上海交通大学医学院附属仁济医院 | MicroRNA-155拮抗剂在制备治疗硬皮病的药物中的应用 |
| CN105251008B (zh) * | 2015-10-26 | 2018-01-26 | 上海交通大学医学院附属仁济医院 | MicroRNA‑155拮抗剂在制备治疗硬皮病的药物中的应用 |
| CN112941074A (zh) * | 2021-01-20 | 2021-06-11 | 青岛大学附属医院 | MicroRNA-302c-3p作为NLRP3抑制剂的应用 |
| CN112941074B (zh) * | 2021-01-20 | 2022-06-28 | 青岛大学附属医院 | MicroRNA-302c-3p作为NLRP3抑制剂的应用 |
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