CN111939272A - Ccn1的新用途 - Google Patents
Ccn1的新用途 Download PDFInfo
- Publication number
- CN111939272A CN111939272A CN202010850212.4A CN202010850212A CN111939272A CN 111939272 A CN111939272 A CN 111939272A CN 202010850212 A CN202010850212 A CN 202010850212A CN 111939272 A CN111939272 A CN 111939272A
- Authority
- CN
- China
- Prior art keywords
- ccn1
- fat transplantation
- seq
- amino acid
- cys
- Prior art date
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Abstract
本发明涉及医药技术领域，特别是涉及CCN1在制备改善脂肪移植存活率或预防脂肪移植术后并发症产品中的用途，所述CCN1包括CCN1基因和CCN1蛋白，所述脂肪移植包括自体脂肪移植，所述改善脂肪移植存活率或降低脂肪移植术后并发症发生率产品的有效成分包括CCN1基因或CCN1蛋白，所述产品包括药物、保健品、食品、过表达体系、细胞。本发明的CCN1在制备改善脂肪移植存活率或预防脂肪移植术后并发症产品中的用途显著改善了脂肪移植的效率和生存率，减少脂肪移植术后并发症的发生率，提高脂肪移植的成功率，减少患者痛苦，降低患者和医疗成本；有助于脂肪移植术的发展。
Description
技术领域
本发明涉及医药技术领域，特别是涉及一种CCN1在制备改善脂肪移植存活率或预防脂肪移植术后并发症产品中的用途。
背景技术
应用自体脂肪游离移植治疗组织缺损和发育不良，已有较长的历史。1893年，Neuber最早完成了用多个自体游离的小脂肪块填充软组织缺损的手术；随后Brunings于1911年报道用注射器注射少量脂肪纠正软组织凹陷。移植脂肪颗粒存在高吸收率和低存活率的问题。Peer的研究发现移植的脂肪颗粒，在体积和质量上减少50％以上，坏死的脂肪颗粒会引起纤维囊性化和假性囊肿。因此，自体脂肪移植半个多世纪以来没有突破性进展。但是，自体脂肪组织作为理想的软组织填充材料，其生物相容性优于人工组织代用品、异体及异种材料，没有免疫排斥现象，并随着20世纪80年代脂肪抽吸技术的发展，脂肪移植再次得到广泛应用，并体现出相当大的优势。但自体脂肪移植依然存在着液化、坏死、感染等并发症、存活率低的问题。
发明内容
鉴于以上所述现有技术的缺点，本发明的目的在于提供一种CCN1在制备改善脂肪移植存活率或预防脂肪移植术后并发症产品中的用途，用于解决现有技术中的问题。
为实现上述目的及其他相关目的，本发明第一方面提供CCN1基因在制备改善脂肪移植存活率或预防脂肪移植术后并发症产品中的用途。
优选的，所述CCN1基因序列如SEQ ID NO.1所示。
第二方面提供CCN1蛋白在制备改善脂肪移植存活率或预防脂肪移植术后并发症产品中的用途。
优选的，所述CCN1蛋白包括以下任一项或几项：
1)如SEQ ID NO.2所示的氨基酸序列；
2)与SEQ ID NO.2所示的氨基酸序列具有80％以上相似性、且具有SEQ ID NO.2所示的氨基酸序列所限定的功能的氨基酸序列；
3)包括四个结构域，四个结构域的氨基酸序列分别如SEQ ID NO.3、SEQ ID NO.4、SEQID NO.5、SEQ ID NO.6所示；
4)与3)中任一个或多个结构域的氨基酸序列相似性达到80％以上。
所述改善脂肪移植存活率或预防脂肪移植术后并发症产品的有效成分包括CCN1基因或CCN1蛋白。
优选的，所述产品可以为药物、保健品、食品、过表达体系、细胞。
如上所述，本发明的CCN1在制备提高脂肪移植存活率或预防脂肪移植术后并发症产品中的用途，具有以下有益效果：显著提高了脂肪移植的效率和生存率，减少脂肪移植术后并发症的发生率，提高脂肪移植的成功率，减少患者痛苦，降低患者和医疗成本；有助于脂肪移植术的发展。
附图说明
图1显示为本发明的动物模型建造方法图：取双侧腹股沟脂肪，注入背部皮下。
图2-1显示为本发明的动物模型建造成功7天后取出的脂肪组织图。
图2-2显示为本发明的动物模型建造成功7天后取出的脂肪组织体积照片(左图)和体积大小统计图(右图)。
图3显示为HE染色结果图。
具体实施方式
本发明第一方面提供CCN1基因在制备改善脂肪移植存活率或预防脂肪移植术后并发症产品中的用途。
进一步的，所述CCN1基因序列如SEQ ID NO.1所示。
所述CCN1基因(又称Cyr61，即cysteine-rich 61或高半胱氨酸蛋白61)基因是即刻早期基因产物之一，作为一种富含半胱氨酸并可与肝素、整合素结合的分泌性蛋白，Cyr61基因的表达可以调节多个基因的转录并参与多种信号传导通路。
所述脂肪移植包括自体脂肪移植。
优选的，所述脂肪移植术选自自体脂肪移植，自体脂肪移植无过敏、无排异、操作简单、生物相容性较佳，没有免疫排斥现象。
第二方面提供CCN1蛋白在制备改善脂肪移植存活率或预防脂肪移植术后并发症产品中的用途。
所述CCN1蛋白为CCN1基因所编码。
具体的，所述CCN1蛋白包括来源于人、鼠、犬、牛、猪等的任一CCN1蛋白序列形成的蛋白。上述不同来源的基础蛋白序列均可以在NCBI中查询。
具体的，所述CCN1蛋白包括以下任一项或几项：
1)如SEQ ID NO.2所示的氨基酸序列；
2)与SEQ ID NO.2所示的氨基酸序列具有80％以上相似性、且具有SEQ ID NO.2所示的氨基酸序列所限定功能的氨基酸序列；
3)包括四个结构域，四个结构域的氨基酸序列分别如SEQ ID NO.3、SEQ ID NO.4、SEQID NO.5、SEQ ID NO.6所示；
4)与3)中任一个或多个结构域的氨基酸序列相似性达到80％以上、且具有相应结构域所限定功能的氨基酸序列。
所述相似性是根据NCBI中BLAST比对的。
CCN1蛋白包括天然CCN1蛋白和重组CCN1蛋白。
具体的，所述改善脂肪移植存活率或降低脂肪移植术后并发症发生率产品的有效成分包括CCN1基因或CCN1蛋白。
所述产品可以为单成分物质，亦可为多成分物质。
具体的，所述产品可以为药物、保健品、食品、过表达体系、细胞。
具体的，所述过表达体系或细胞为以慢病毒、腺病毒、质粒作为载体构建的CCN1基因过表达体系、细胞。
本发明提供的改善脂肪移植存活率或降低脂肪移植术后并发症发生率的药物包括CCN1基因或CCN1蛋白与药学上可接受的药物载体或辅料。
具体的，所述CCN1蛋白包括以下任一项或几项：
1)如SEQ ID NO.2所示的氨基酸序列；
2)与SEQ ID NO.2所示的氨基酸序列具有80％以上相似性、且具有SEQ ID NO.2所示的氨基酸序列所限定功能的氨基酸序列；
3)包括四个结构域，四个结构域的氨基酸序列分别如SEQ ID NO.3、SEQ ID NO.4、SEQID NO.5、SEQ ID NO.6所示；
4)与3)中任一个或多个结构域的氨基酸序列相似性达到80％以上、且具有相应结构域所限定功能的氨基酸序列。
“药学上可接受的”是指当分子本体和组合物适当地给予动物或人时，它们不会产生不利的、过敏的或其它不良反应。
更进一步的，所述药学上可接受的药物载体包含肠溶衣制剂、胶囊、微球/囊、脂质体、微乳液、复乳液、纳米颗粒、磁颗粒、壳聚糖、明胶或凝胶中的一种或一种以上。
更进一步的，药学上可接受的辅料应当与所述有效成分相容，即能与其共混而不会在通常情况下大幅度降低药物的效果。可作为药学上可接受的载体或辅料的一些物质的具体例子是糖类，如乳糖、葡萄糖和蔗糖；淀粉，如玉米淀粉和土豆淀粉；纤维素及其衍生物，如甲基纤维素钠、乙基纤维素和甲基纤维素；西黄蓍胶粉末；麦芽；明胶；滑石；固体润滑剂，如硬脂酸和硬脂酸镁；硫酸钙；植物油，如花生油、棉籽油、芝麻油、橄榄油、玉米油和可可油；多元醇，如丙二醇、甘油、山梨糖醇、甘露糖醇和聚乙二醇；海藻酸；乳化剂，如Tween；润湿剂，如月桂基硫酸钠；着色剂；调味剂；压片剂、稳定剂；抗氧化剂；防腐剂；无热原水；等渗盐溶液；和磷酸盐缓冲液等。这些物质根据需要用于帮助配方的稳定性或有助于提高活性或它的生物有效性或在口服的情况下产生可接受的口感或气味。
本发明中，除非特别说明，药物剂型并无特别限定，可以被制成针剂、口服液、片剂、胶囊、滴丸、喷剂等剂型，可通过常规方法进行制备。药物剂型的选择应与给药方式相匹配。
本发明提供的药物为注射剂，以注射剂的总体积为基准计算，所述注射剂包括以下组分：2μg/ml-100μg/ml CCN1蛋白、人血白蛋白、甘油、甘露醇、溶剂为水。
具体的，所述CCN1蛋白的浓度选自以下任一浓度范围：2μg/ml-10μg/ml、10μg/ml-20μg/ml、20μg/ml-30μg/ml、30μg/ml-40μg/ml、40μg/ml-50μg/ml、50μg/ml-60μg/ml、60μg/ml-70μg/ml、70μg/ml-80μg/ml、80μg/ml-90μg/ml、90μg/ml-100μg/ml。
以上组分中人血白蛋白、甘油、甘露醇的浓度不做具体限制，只要保证CCN1蛋白的有效浓度即可。
在一种实施方式中，所述注射剂包括以下质量体积分数的组分：2μg/ml-100μg/mlCCN1蛋白、0.2mg/ml-2mg/ml人血白蛋白、70mg/ml-150mg/ml甘油、5mg/ml-50mg/ml甘露醇。
具体的，所述CCN1蛋白包括以下任一项或几项：
1)如SEQ ID NO.2所示的氨基酸序列；
2)与SEQ ID NO.2所示的氨基酸序列具有80％以上相似性、且具有SEQ ID NO.2所示的氨基酸序列所限定功能的氨基酸序列；
3)包括四个结构域，四个结构域的氨基酸序列分别如SEQ ID NO.3、SEQ ID NO.4、SEQID NO.5、SEQ ID NO.6所示；
4)与3)中任一个或多个结构域的氨基酸序列相似性达到80％以上、且具有相应结构域所限定功能的氨基酸序列。
进一步的，所述注射剂选自注射液。
所述注射剂可通过肌肉注射、皮下注射或者静脉注射。
以下通过特定的具体实例说明本发明的实施方式，本领域技术人员可由本说明书所揭露的内容轻易地了解本发明的其他优点与功效。本发明还可以通过另外不同的具体实施方式加以实施或应用，本说明书中的各项细节也可以基于不同观点与应用，在没有背离本发明的精神下进行各种修饰或改变。
在进一步描述本发明具体实施方式之前，应理解，本发明的保护范围不局限于下述特定的具体实施方案；还应当理解，本发明实施例中使用的术语是为了描述特定的具体实施方案，而不是为了限制本发明的保护范围；在本发明说明书和权利要求书中，除非文中另外明确指出，单数形式“一个”、“一”和“这个”包括复数形式。
当实施例给出数值范围时，应理解，除非本发明另有说明，每个数值范围的两个端点以及两个端点之间任何一个数值均可选用。除非另外定义，本发明中使用的所有技术和科学术语与本技术领域技术人员通常理解的意义相同。除实施例中使用的具体方法、设备、材料外，根据本技术领域的技术人员对现有技术的掌握及本发明的记载，还可以使用与本发明实施例中所述的方法、设备、材料相似或等同的现有技术的任何方法、设备和材料来实现本发明。
重组人CCN1蛋白(rhCCN1)为从PEPROTECH公司购买，货号120-25，由大肠杆菌表达，分子量为39.5kDa，由357个氨基酸残基组成。使用前用0.1％人血白蛋白(w/v)溶解重组人CCN1蛋白冻干粉，使其浓度为0.2mg/ml，分装，于-20℃保存。
实施例1rhCCN1针剂注射液的配置：
取1g甘油、100mg甘露醇溶于10ml灭菌注射用水中，混匀。取2mg人血白蛋白，20μgrhCCN1，溶于上述溶液中。震荡混匀，0.22μm滤器过滤，制成注射剂，4度保存(空白注射液为不添加rhCCN1的注射剂)。
实施例2自体脂肪移植实验
使用4周大的SD大鼠，取双侧腹股沟脂肪并剪碎，注入背部皮下1ml脂肪(如图1所示)，次日起连续注射实施例1中配制的注射剂每天一次，持续7天。实验分为实验组和对照组，每组5只大鼠，实验组每只大鼠注射200μl浓度为2μg/ml的CCN1注射液，对照组每只大鼠注射200μl PBS，7天后取出脂肪组织，通过现有技术中的排水法(即将脂肪组织放入盛有水的容器中，记录放入前后水的体积差即为脂肪组织的体积)测量脂肪体积。
结果如图2-1所示，CCN1组脂肪状态良好，而对照组呈现脂肪坏死、液化状态。如图2-2所示，经过观察和排水法检测移植后的脂肪体积，CCN1组的脂肪组织体积显著大于对照组体积。
实施例3HE染色
固定：取实施例2中的脂肪组织迅速置于10％甲醛中固定。
脱水透明：用酒精做脱水剂逐渐脱去组织块中的水份。再将组织块置于既溶于酒精、又溶于石蜡的透明剂二甲苯中透明，以二甲苯替换出组织块的中酒精。
浸蜡包埋：将已透明的组织块置于已溶化的石蜡中，放入溶蜡箱保温。待石蜡完全浸入组织块后进行包埋：先制备好容器(如折叠一小纸盒)，倒入已溶化的石蜡，迅速夹取已浸透石蜡的组织块放入其中。冷却凝固成块即可。包埋好的组织块变硬，才能在切片机上切成很薄的切片。
切片与贴片：将包埋好的蜡块固定于切片机上，切成薄片，一般为5—8微米厚。切下的薄片往往皱折，要放到加热的水中烫平，再贴到载玻片上，放45℃恒温箱中烘干。
脱蜡：用二甲苯Ⅰ、Ⅱ脱蜡各10分钟，事先准备好盖玻片。覆水，用100％、90％、80％、70％的酒精各5分钟，自来水冲洗三次，每次5分钟。
苏木精染色：苏木精染色5分钟，根据染色情况，可以适当增加或减少染色时间，流水冲洗。5％乙酸分化1分钟，流水冲洗，用吸管滴加乙酸，布满玻片上的组织即可，分化后颜色变浅了一些，成为蓝色。
返蓝：返蓝液返蓝。
伊红染色：染色1分钟，根据染色情况，可以适当增加或减少染色时间，流水冲洗。
脱水：用70％、80％、90％、100％酒精各脱水10秒，再经二甲苯1分钟，可以在通风橱自然晾干再封片，约5分钟左右。
封片：滴上中性树胶，封片，用吸管滴上一滴即可，尽量少滴，但压片后要将组织全部覆盖完，避免中间有气泡。
结果如图3所示，CCN1组脂肪细胞完好，脂肪颗粒匀称，而对照组(BC组)有明显的炎症细胞浸润，脂肪颗粒较小，空泡变性严重。
脂肪移植存活率和脂肪移植并发症发生率见表1。脂肪移植存活率的计算方法如下：每张切片显微镜下随机选取5个视野，分别计数后计算存活率取平均数。并发症采用肉眼观察的方式，发生率统计中包括脂肪液化、坏死和感染并发症。
表1自体脂肪移植实验脂肪移植存活率和脂肪移植并发症发生率统计
| 实验组 | 对照组 | |
| 脂肪移植存活率 | 80％ | 20％ |
| 脂肪移植并发症发生率 | 10％ | 80％ |
以上的实施例是为了说明本发明公开的实施方案，并不能理解为对本发明的限制。此外，本文所列出的各种修改以及发明中方法、组合物的变化，在不脱离本发明的范围和精神的前提下对本领域内的技术人员来说是显而易见的。虽然已结合本发明的多种具体优选实施例对本发明进行了具体的描述，但应当理解，本发明不应仅限于这些具体实施例。事实上，各种如上所述的对本领域内的技术人员来说显而易见的修改来获取发明都应包括在本发明的范围内。
序列表
<110> 上海交通大学医学院附属第九人民医院
<120> CCN1的新用途
<160> 6
<170> SIPOSequenceListing 1.0
<210> 1
<211> 4468
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 1
aagctttggg acttgttccg aacacgcctc tttgaagtcc acaaatattc ctgactcaga 60
gacacactcc tcttccccgt tctactcttt caacagataa cttgcctctc accttcgctg 120
taaacaagca aacagctcac tgccttcccg ggtgagggct tcagtggctg cccggtcaac 180
tcgcatcacc aaacaaaacg acttttgttc ctccctctca ggtcctccca cccacccagt 240
ccaggcaaag ttctgaactg gcccccctcg cccctcacga ccctccaact accatcacca 300
ccatcacgcc ccaaagaacc cttcccaaca taagtcgtaa tttaaggtgg aaaaaacgaa 360
ctgttttctt gacgggtctg ggacacacac acacacacac acacacacac acacacacac 420
cgaactgttt tcttgacggg tctgggagac agacagacac acacacacac acacacacac 480
acacacacac acacaaaggt gcaatggagc caggggaggc gcttggcagc agcccgcgcc 540
aaccagcatt cctgagatgt ttgagaattc tggaacgcgc agacagagcc gacgtcactg 600
caacacgcgg cgcctccgcc ggcccgtata aaaggcgggc tccggggcgc ctgggcagac 660
cgcgagcgag agcgcccccg agcagcgccc gcgccctccg cgccttctcc gccgggacct 720
cgagcgaaag acgcccgccc gccgcccagc cctcgcctcc ctgcccaccg ggcacaccgc 780
gccgccaccc cgaccccgct gcgcacggcc tgtccgctgc acaccagctt gttggcgtct 840
tcgtcgccgc gctcgccccg ggctactcct gcgcgccaca atgagctccc gcatcgccag 900
ggcgctcgcc ttagtcgtca cccttctcca cttgaccagg ctggtgagtt ggactctcct 960
tttgccacct attccccgtc cgctctccag ccccttcccc tggtcccaga ttgcccacgg 1020
caggaaaagt taaaaagttc gcgatcgttt gcgggtagcc gtttctttaa gcactctccc 1080
cctccccccg aagacgtgtc gggacctctt ggtgggagca gccttccgag gtggccaggc 1140
tggacgagat cagaggctcc ccgtcgatag ggtcggagac ccccgtccct cactgcggca 1200
gccgcggcgc ccctcctgcg caccgcgccg agtctcacgc gtatcttctc ccccttccag 1260
gcgctctcca cctgccccgc tgcctgccac tgccccctgg aggcgcccaa gtgcgcgccg 1320
ggagtcgggc tggtccggga cggctgcggc tgctgtaagg tctgcgccaa gcagctcaac 1380
gaggactgca gcaaaacgca gccctgcgac cacaccaagg ggctggaatg caacttcggc 1440
gccagctcca ccgctctgaa ggggatctgc agaggtaaga tgcttgtggt ttggcccctt 1500
taaaaagaat actagtcccc atagtccaga agtttagtaa ttctgagacc atgtatggtg 1560
atgctttgtt gttggtagct tggcagaaag gcacatgatt tcagcagtct ggaatgcaat 1620
tcagtgtgtc tgggcccaac gaaagcgcat acggaaaagt gattcctgac taacttattg 1680
ttctggtctg gagtctccgg ggaattgtag ggaactttac cataaattga atttaacagc 1740
agaaaatatg tatgagtttc aggcggtggt ttggaatctt aactttatcc ccttctacct 1800
ttctcttttg ggtgatcttt gcagctcagt cagagggcag accctgtgaa tataactcca 1860
gaatctacca aaacggggaa agtttccagc ccaactgtaa acatcagtgc acatgtattg 1920
atggcgccgt gggctgcatt cctctgtgtc cccaagaact atctctcccc aacttgggct 1980
gtcccaaccc tcggctggtc aaagttaccg ggcagtgctg cgaggagtgg gtctgtgacg 2040
aggatagtat caaggacccc atggaggacc aggacggcct ccttggcaag gagctgggat 2100
tcgatgcctc cgaggtggag ttgacgagaa acaatgaatt gattgcagtt ggaaaaggca 2160
gctcactgaa gcggctccct ggtaagtgga gactgagcac ttcagacact gtactgagat 2220
gcatttctgg tctaaatctt tgtagaaatg agtgcttgag cctgtttgtg tcggtatgcc 2280
tctgagaagt cttccctctt atatgtctct agtttttgga atggagcctc gcatcctata 2340
caacccttta caaggccaga aatgtattgt tcaaacaact tcatggtccc agtgctcaaa 2400
gacctgtgga actggtatct ccacacgagt taccaatgac aaccctgagt gccgccttgt 2460
gaaagaaacc cggatttgtg aggtgcggcc ttgtggacag ccagtgtaca gcagcctgaa 2520
agtaagttcc ttcagggaca gtgtagactg ttgcctggca ggtgggtggg atgtgaacat 2580
ctttttgaag aaagagaaat atcaccccta actttccttc tctcctttct cttacagaag 2640
ggcaagaaat gcagcaagac caagaaatcc cccgaaccag tcaggtttac ttacgctgga 2700
tgtttgagtg tgaagaaata ccggcccaag tactgcggtt cctgcgtgga cggccgatgc 2760
tgcacgcccc agctgaccag gactgtgaag atgcggttcc gctgcgaaga tggggagaca 2820
ttttccaaga acgtcatgat gatccagtcc tgcaaatgca actacaactg cccgcatgcc 2880
aatgaagcag cgtttccctt gtacaggctg ttcaatgaca ttcacaaatt tagggactaa 2940
atgctacctg ggtttccagg gcacacctag acaaacaagg gagaagagtg tcagaatcag 3000
aatcatggag aaaatgggcg ggggtggtgt gggtgatggg actcattgta gaaaggaagc 3060
cttgctcatt cttgaggagc attaaggtat ttcgaaactg ccaagggtgc tggtgcggat 3120
ggacactaat gcagccacga ttggagaata ctttgcttca tagtattgga gcacatgtta 3180
ctgcttcatt ttggagcttg tggagttgat gactttctgt tttctgtttg taaattattt 3240
gctaagcata ttttctctag gcttttttcc ttttggggct tctacagtcg taaaagagat 3300
aataagatta gttggacagt ttaaagcttt tattcgtcct ttgacaaaag taaatgggag 3360
ggcattccat cccttcctga agggggacac tccatgagtg tctgtgagag gcagctatct 3420
gcactctaaa ctgcaaacag aaatcaggtg ttttaagact gaatgtttta tttatcaaaa 3480
tgtagctttt ggggagggag gggaaatgta atactggaat aatttgtaaa tgattttaat 3540
tttatattca gtgaaaagat tttatttatg gaattaacca tttaataaag aaatatttac 3600
ctaatatctg agtgtatgcc attcggtatt tttagaggtg ctccaaagtc attaggaaca 3660
acctagctca cgtactcaat tattcaaaca ggacttattg ggatacagca gtgaattaag 3720
ctattaaaat aagataatga ttgcttttat accttcagta gagaaaagtc tttgcatata 3780
aagtaatgtt taaaaaacat gtattgaaca cgacattgta tgaagcacaa taaagattct 3840
gaagctaaat ttgtgattta agaaaacagc gcttcatgtt catcagaata taaagcctaa 3900
gggtctccat cactctgtga gatggctata ataatttatt attttaatca ccaggttagt 3960
gggcatgcca ctttagtaga gtagagaaac cctttaatga aaaggggtag tccataactc 4020
aggctgccac atccagaccc atgggcaaga ttgaatataa ttaatgtatt ctaaagactg 4080
cttgtttata cctttatatt ttcccaatac cgttcctaaa aattagaact acttagaaat 4140
ttacccttgg ctgttatgag gaaaaatctg agtctatagg agtcagtttg ttttcactaa 4200
atgagcttga agcatgactt gtgttaatcc taataagccg gtgattaggt aaacatgctg 4260
ttaaatgcaa aggaatgcaa ggaatttcaa gtacttttcc aatagcgtga gggccaagct 4320
accccatccc cctttccttt ttataatata cgttatattg atgggggagg gagcagttat 4380
atagaagttg gctattcaga aggtcaaagg tccagagcat tcctaaaaga aagggaccca 4440
aatcataggt ctaggagagg ttgagaag 4468
<210> 2
<211> 381
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 2
Met Ser Ser Arg Ile Ala Arg Ala Leu Ala Leu Val Val Thr Leu Leu
1 5 10 15
His Leu Thr Arg Leu Ala Leu Ser Thr Cys Pro Ala Ala Cys His Cys
20 25 30
Pro Leu Glu Ala Pro Lys Cys Ala Pro Gly Val Gly Leu Val Arg Asp
35 40 45
Gly Cys Gly Cys Cys Lys Val Cys Ala Lys Gln Leu Asn Glu Asp Cys
50 55 60
Ser Lys Thr Gln Pro Cys Asp His Thr Lys Gly Leu Glu Cys Asn Phe
65 70 75 80
Gly Ala Ser Ser Thr Ala Leu Lys Gly Ile Cys Arg Ala Gln Ser Glu
85 90 95
Gly Arg Pro Cys Glu Tyr Asn Ser Arg Ile Tyr Gln Asn Gly Glu Ser
100 105 110
Phe Gln Pro Asn Cys Lys His Gln Cys Thr Cys Ile Asp Gly Ala Val
115 120 125
Gly Cys Ile Pro Leu Cys Pro Gln Glu Leu Ser Leu Pro Asn Leu Gly
130 135 140
Cys Pro Asn Pro Arg Leu Val Lys Val Thr Gly Gln Cys Cys Glu Glu
145 150 155 160
Trp Val Cys Asp Glu Asp Ser Ile Lys Asp Pro Met Glu Asp Gln Asp
165 170 175
Gly Leu Leu Gly Lys Glu Leu Gly Phe Asp Ala Ser Glu Val Glu Leu
180 185 190
Thr Arg Asn Asn Glu Leu Ile Ala Val Gly Lys Gly Ser Ser Leu Lys
195 200 205
Arg Leu Pro Val Phe Gly Met Glu Pro Arg Ile Leu Tyr Asn Pro Leu
210 215 220
Gln Gly Gln Lys Cys Ile Val Gln Thr Thr Ser Trp Ser Gln Cys Ser
225 230 235 240
Lys Thr Cys Gly Thr Gly Ile Ser Thr Arg Val Thr Asn Asp Asn Pro
245 250 255
Glu Cys Arg Leu Val Lys Glu Thr Arg Ile Cys Glu Val Arg Pro Cys
260 265 270
Gly Gln Pro Val Tyr Ser Ser Leu Lys Lys Gly Lys Lys Cys Ser Lys
275 280 285
Thr Lys Lys Ser Pro Glu Pro Val Arg Phe Thr Tyr Ala Gly Cys Leu
290 295 300
Ser Val Lys Lys Tyr Arg Pro Lys Tyr Cys Gly Ser Cys Val Asp Gly
305 310 315 320
Arg Cys Cys Thr Pro Gln Leu Thr Arg Thr Val Lys Met Arg Phe Arg
325 330 335
Cys Glu Asp Gly Glu Thr Phe Ser Lys Asn Val Met Met Ile Gln Ser
340 345 350
Cys Lys Cys Asn Tyr Asn Cys Pro His Ala Asn Glu Ala Ala Phe Pro
355 360 365
Phe Tyr Arg Leu Phe Asn Asp Ile His Lys Phe Arg Asp
370 375 380
<210> 3
<211> 70
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 3
Thr Cys Pro Ala Ala Cys His Cys Pro Leu Glu Ala Pro Lys Cys Ala
1 5 10 15
Pro Gly Val Gly Leu Val Arg Asp Gly Cys Gly Cys Cys Lys Val Cys
20 25 30
Ala Lys Gln Leu Asn Glu Asp Cys Ser Lys Thr Gln Pro Cys Asp His
35 40 45
Thr Lys Gly Leu Glu Cys Asn Phe Gly Ala Ser Ser Thr Ala Leu Lys
50 55 60
Gly Ile Cys Arg Ala Gln
65 70
<210> 4
<211> 67
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 4
Arg Pro Cys Glu Tyr Asn Ser Arg Ile Tyr Gln Asn Gly Glu Ser Phe
1 5 10 15
Gln Pro Asn Cys Lys His Gln Cys Thr Cys Ile Asp Gly Ala Val Gly
20 25 30
Cys Ile Pro Leu Cys Pro Gln Glu Leu Ser Leu Pro Asn Leu Gly Cys
35 40 45
Pro Asn Pro Arg Leu Val Lys Val Thr Gly Gln Cys Cys Glu Glu Trp
50 55 60
Val Cys Asp
65
<210> 5
<211> 46
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 5
Lys Cys Ile Val Gln Thr Thr Ser Trp Ser Gln Cys Ser Lys Thr Cys
1 5 10 15
Gly Thr Gly Ile Ser Thr Arg Val Thr Asn Asp Asn Pro Glu Cys Arg
20 25 30
Leu Val Lys Glu Thr Arg Ile Cys Glu Val Arg Pro Cys Gly
35 40 45
<210> 6
<211> 75
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 6
Cys Ser Lys Thr Lys Lys Ser Pro Glu Pro Val Arg Phe Thr Tyr Ala
1 5 10 15
Gly Cys Leu Ser Val Lys Lys Tyr Arg Pro Lys Tyr Cys Gly Ser Cys
20 25 30
Val Asp Gly Arg Cys Cys Thr Pro Gln Leu Thr Arg Thr Val Lys Met
35 40 45
Arg Phe Arg Cys Glu Asp Gly Glu Thr Phe Ser Lys Asn Val Met Met
50 55 60
Ile Gln Ser Cys Lys Cys Asn Tyr Asn Cys Pro
65 70 75
Claims (10)
1.CCN1基因或CCN1蛋白在制备改善脂肪移植存活率或预防脂肪移植术后并发症产品中的用途。
2.根据权利要求1所述的用途，其特征在于，所述CCN1基因编码CCN1蛋白。
3.根据权利要求2所述的用途，其特征在于，所述CCN1基因的核苷酸序列如SEQ IDNO.1所示。
4.根据权利要求1或2所述的用途，其特征在于，所述CCN1蛋白包括以下任一项或几项：
1)如SEQ ID NO.2所示的氨基酸序列；
2)与SEQ ID NO.2所示的氨基酸序列具有80％以上相似性、且具有SEQ ID NO.2所示的氨基酸序列所限定功能的氨基酸序列；
3)包括四个结构域，四个结构域的氨基酸序列分别如SEQ ID NO.3、SEQ ID NO.4、SEQID NO.5和SEQ ID NO.6所示；
4)与3)中任一个或多个结构域的氨基酸序列相似性达到80％以上、且具有相应结构域所限定功能的氨基酸序列。
5.根据权利要求1所述的用途，其特征在于，所述脂肪移植包括自体脂肪移植。
6.根据权利要求1所述的用途，其特征在于，所述改善脂肪移植存活率或预防脂肪移植术后并发症产品的有效成分包括CCN1基因或CCN1蛋白。
7.根据权利要求1所述的用途，其特征在于，所述产品包括药物、保健品、食品、过表达体系、细胞。
8.根据权利要求7所述的用途，其特征在于，所述药物包括CCN1基因或CCN1蛋白与药学上可接受的药物载体或辅料。
9.根据权利要求7所述的用途，其特征在于，所述药物为注射剂，以注射剂的总体积为基准，所述注射剂包括以下组分：CCN1蛋白、人血白蛋白、甘油、甘露醇、溶剂为水，其中所述CCN1蛋白的终浓度为2μg/ml-100μg/ml。
10.根据权利要求9所述的用途，其特征在于，以注射剂的总体积为基准，所述注射剂包括以下质量体积浓度的组分：2μg/ml-100μg/ml CCN1蛋白、0.2mg/ml-2mg/ml人血白蛋白、70mg/ml-150mg/ml甘油、5mg/ml-50mg/ml甘露醇。
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| CN1447819A (zh) * | 2000-01-31 | 2003-10-08 | 妙甯公司 | 人cyr61 |
| WO2006099421A2 (en) * | 2005-03-14 | 2006-09-21 | The Board Of Trustees Of The Leland Stanford Junior University | Methods and compositions for evaluating graft survival in a solid organ transplant recipient |
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| CN1447819A (zh) * | 2000-01-31 | 2003-10-08 | 妙甯公司 | 人cyr61 |
| WO2006099421A2 (en) * | 2005-03-14 | 2006-09-21 | The Board Of Trustees Of The Leland Stanford Junior University | Methods and compositions for evaluating graft survival in a solid organ transplant recipient |
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