基于TGF-β1和Bcl-2的抗干眼症中药高通量筛选体系的建立及验证

Now dry eye treatment is not ideal. All kinds of western medicine have their own limitations, efficacy are not satisfied. People need innovative drugs appears. High throughput screening system has gradually become the main method of drug screening. Point of the establishment of screening system is drug targets. The key drug targets of dry eye are TGF-β1/Sp-1 protein (Inflammatory molecular targets), Bcl-2/p53 protein (Apoptotic molecular targets) and LGEC (cell target). From these, the use of genetic engineering and genetically modified technology, high-throughput screening system of anti-dry eye is established. Successful establishment of system provides the key common technology for drug screening of anti-dry eye, and using the system for high-throughput screening of traditional Chinese medicine, in favor of research and development of new drug..Early study shows Buddleia granules, traditional Chinese medicine, has suppression for dry eye. Buddleia granules can inhibit lacrimal local inflammatory response and apoptosis. In order to verify the screening system that is established, the research will prepare component into group to screen effective components of anti-dry eye.

现有的干眼症的治疗方法并不理想，各类西药均有各自局限性，疗效不满意，亟需创新药物出现。高通量筛选体系已逐渐成为药物筛选的主要方法。筛选体系建立的要点在于药靶。干眼症的关键药靶是TGF-β1/Sp-1（炎症分子靶标）、Bcl-2/p53蛋白（凋亡分子靶标）和LGEC（细胞靶标）。本研究从此入手，采用基因工程技术和转基因技术，建立抗干眼症的高通量筛选体系。体系的成功建立，将为干眼症的药物筛选提供关键共性技术，利用该体系对中药组分库进行高通量筛选，有利于新药的研发。.前期研究表明密蒙花颗粒对于干眼症有良好的治疗作用，能抑制泪腺炎症反应和细胞凋亡。为了验证所建立的筛选体系，本研究将制备密蒙花颗粒剂中药组分库，利用该体系进行抗干眼症的有效组分筛选，并将筛选结果进行动物模型验证。若验证成功，不仅能证明所建立的筛选体系的实用性，也能找出密蒙花颗粒剂抗干眼症的有效组分，有助于创新药物的发现。

现有的干眼症的治疗方法并不理想，各类西药均有各自局限性，疗效不满意，亟需创新药物出现。.干眼症的关键药靶是TGF-β1/Sp-1（炎症分子靶标）、Bcl-2/p53蛋白（凋亡分子靶标）和LGEC（细胞靶标）。.本研究从此入手，采用基因工程技术和转基因技术，建立了两种抗干眼症的高通量筛选体系，1号体系以TGF-β1/Sp-1（炎症分子靶标）为药靶，2号体系以Bcl-2/p53蛋白（凋亡分子靶标）为药靶。体系的成功建立，为干眼症的药物筛选提供了关键共性技术。.制备溶剂分离联合大孔树脂分离的方法建立了密蒙花中药组分库，利用该体系对中药组分库进行高通量筛选。筛选出有效组份2-2-2、2-2-3，并将筛选结果进行动物模型验证。.密蒙花有效组分能够有效抑制泪腺组织中Caspase-9蛋白、Akt蛋白、PI3K蛋白、ICAM-1蛋白、IL-6蛋白、IL-17蛋白的表达，反应了筛选出的密蒙花有效组分能够有效抑制泪腺组织的局部炎症反应和细胞凋亡。