CN111979312A - 一种用于增生性瘢痕诊断和治疗的LncRNA生物标志物 - Google Patents
一种用于增生性瘢痕诊断和治疗的LncRNA生物标志物 Download PDFInfo
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Abstract
本发明提供了一种用于增生性瘢痕诊断和治疗的LncRNA生物标志物，本发明基于本发明的生物标志物LncRNA TRHDE‑AS1的表达水平，来确定受试者是否有增生性瘢痕发生的可能；本发明提供基于PTEN蛋白表达水平，为增生性瘢痕患者进行治疗。
Description
技术领域
本发明涉及生物医疗技术领域，具体为一种用于增生性瘢痕诊断和治疗的LncRNA生物标志物。
背景技术
增生性瘢痕是一种发生于外伤或严重烧伤后的成纤维细胞增生性疾病，主要特点是过度细胞外基质沉积和成纤维细胞的侵袭性生长。增生性瘢痕可以导致生理、心理和社会不适，严重影响患者生活质量。增生性瘢痕的形成机制不清楚，无有效预防治疗方法，治疗措施一般采用手术、激光切除，硅凝胶外敷，穿着压力服，或类固醇注射，但效果欠佳。
发明内容
本发明的第一个目的在于通过LncRNA TRHDE-AS1过表达来抑制PTEN蛋白表达，从而抑制瘢痕的形成。
本发明的另一个目的提供了一种预测增生性瘢痕的方法，可通过检测受伤局部组织中LncRNA TRHDE-AS1的表达水平，预测增生性瘢痕的发生。
本发明提供了LncRNA TRHDE-AS1在检测和治疗增生性瘢痕中的应用。
一种LncRNA TRHDE-AS1其表达产物或特异性检测PTEN蛋白表达产物的用途，其特征在于：用于作为增生性瘢痕的诊断和治疗靶点。
进一步地：所述特异性检测PTEN蛋白其表达产物选自成纤维细胞增殖，成纤维细胞增殖会促进成纤维细胞凋亡。
进一步地:其LncRNA TRHDE-AS1作用的载体为miRNA。
进一步地：所述的过程包括LncRNA TRHDE-AS1可以与miRNA结合，从而抑制PTEN蛋白表达，进而抑制成纤维细胞增殖，促进成纤维细胞凋亡，抑制瘢痕形成。
进一步地：LncRNA TRHDE-AS1在检测和治疗增生性瘢痕中的用途。
进一步地：所述组合物包括LncRNA TRHDE-AS1表达水平的试剂；优选的，所述试剂用于检测受伤局部组织中LncRNA TRHDE-AS1的表达水平。
进一步地：所述药物组合物包括LncRNA TRHDE-AS1过表达的药物；优选的，所述药物提高了LncRNA TRHDE-AS1的表达水平；优选的，所述药物组合物还包括药学上可接受的载体。
进一步地：将含有LncRNA TRHDE-AS1过表达的慢病毒或腺病毒载体的药物，应用于创伤/瘢痕局部。
与现有技术相比，本发明的增益效果是:
研究中发现LncRNA TRHDE-AS1在增生性瘢痕患者局部组织中表达降低，进一步研究发现LncRNA TRHDE-AS1可以与miRNA结合，抑制PTEN蛋白表达，进而抑制成纤维细胞增殖，促进成纤维细胞凋亡，抑制瘢痕形成。因此，LncRNA TRHDE-AS1可作为增生性瘢痕的诊断和治疗靶点,从而可用含有LncRNA TRHDE-AS1载体来检测和治疗增生性瘢痕。
LncRNA表达水平检测方便，特异性好，灵敏度高，结果可靠；LncRNA TRHDE-AS1过表达载体易于人工合成，成本低，局部注射或外部使用较为方便，且副作用少，便于病人使用。
具体实施方式
本发明经过多次深入研究，增生性瘢痕患者患部LncRNA TRHDE-AS1表达水平降低，从而导致患者患部PTEN蛋白表达水平显著高于正常水平，提高LncRNA TRHDE-AS1表达水平可以抑制增生性瘢痕产生。
本发明中所使用的“标志物”指称个体中正常或异常进展的指征或个体中疾病或其他状态的指征或表现这些的靶分子。更详细地，“标志物”为正常或异常，以及若是异常，则为与慢性或急性的特定生理学状态或进展的存在相关的解剖学、生理学、生物化学或分子学参数。生物标志物可通过包括实验室检测和医学成像的多种方法来进行检测及测定。
本发明中所使用的“生物标志物水平”及“水平”为利用从生物样本检测生物标志物的任意分析方法来进行测定，并且，在上述生物样本中，为了指称表示生物标志物的、用于生物标志物的、或对应于生物标志物的存在、不存在，绝对量或浓度、相对量或浓度、滴定量、水平、表达水平、测定的水平的比率等的测定值而混用。
实验步骤：
将LncRNA TRHDE-AS1与生物工程所用的慢性病毒或腺病毒通过人工合成方法制成含有LncRNA TRHDE-AS1过表达的慢病毒或腺病毒载体。
实验组：
含有LncRNA TRHDE-AS1过表达的慢病毒或腺病毒载体；
对照组：
未含有LncRNA TRHDE-AS1的生物工程制作的慢病毒或腺病毒载体；
将实验组和对照组合成的病毒载体均分别与多个增生性瘢痕组织进行组织培养；在组织培养过程中对组织中miRNA和PTEN蛋白表达水平进行检测；
检测结果表明，实验组中miRNA和PTEN蛋白表达水平均逐渐降低并趋于正常，而各个对照组中PTEN蛋白表达水平仍高于正常水平；此外，对照组中LncRNA TRHDE-AS1表达水平低于正常水平。
最终结果表明，LncRNA TRHDE-AS1过表达的慢病毒或腺病毒载体能够通过与miRNA结合，能够有效抑制PTEN蛋白的表达水平，从而抑制成纤维细胞增殖，促进成纤维细胞凋亡，抑制瘢痕形成；另一方面，也提供了一种检测增生性瘢痕的方法，可通过检测受伤局部组织中LncRNA TRHDE-AS1的表达水平，来预测增生性瘢痕的发生。
最后应说明的是：以上各实施例仅用以说明本发明的技术方案，而非对其限制；尽管参照前述各实施例对本发明进行了详细的说明，本领域的普通技术人员应当理解：其依然可以对前述各实施例所记载的技术方案进行修改，或者对其中部分或者全部技术特征进行等同替换；而这些修改或者替换，并不使相应技术方案的本质脱离本发明各实施例技术方案的范围。
Claims (8)
1.一种LncRNA TRHDE-AS1其表达产物或特异性检测PTEN蛋白表达产物的用途，其特征在于：用于作为增生性瘢痕的诊断和治疗靶点。
2.根据权利要求1所述的用途，其特征在于：所述特异性检测PTEN蛋白其表达产物选自成纤维细胞增殖，成纤维细胞增殖会促进成纤维细胞凋亡。
3.一种用于增生性瘢痕诊断和治疗的LncRNA生物标志物，其特征在于:其LncRNATRHDE-AS1的作用载体为miRNA。
4.根据权利要求3所述的过程，其特征在于：所述的过程包括LncRNA TRHDE-AS1可以与miRNA结合，从而抑制PTEN蛋白表达水平，进而抑制成纤维细胞增殖，促进成纤维细胞凋亡，抑制瘢痕形成。
5.LncRNA TRHDE-AS1在检测和治疗增生性瘢痕中的用途。
6.根据权利要求5所述的用途，其特征在于：所述组合物包括LncRNA TRHDE-AS1表达水平的试剂；优选的，所述试剂用于检测受伤局部组织中LncRNA TRHDE-AS1的表达水平。
7.一种药物组合物，其特征在于：所述药物组合物包括LncRNA TRHDE-AS1过表达的药物；优选的，所述药物提高了LncRNA TRHDE-AS1的表达水平；优选的，所述药物组合物还包括药学上可接受的载体。
8.一种抑制瘢痕形成的方法，其特征在于：将含有LncRNA TRHDE-AS1过表达的慢病毒或腺病毒载体的药物，应用于创伤/瘢痕局部。
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