CN114939167A - Integrin/ROCK信号通路靶向调控剂在制备修复细胞骨架损伤修复药物的应用 - Google Patents
Integrin/ROCK信号通路靶向调控剂在制备修复细胞骨架损伤修复药物的应用 Download PDFInfo
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Abstract
Integrin/ROCK信号通路靶向调控剂在制备修复细胞骨架损伤修复药物的应用，二甲双胍能通过调控Integrin/ROCK信号通路促进细胞骨架损伤后重塑，抑制ROS释放，逆转细胞的氧化损伤，修复损伤后细胞骨架及形态的改变，减少房水流出通道中细胞外基质沉积，以达到保护房水流出通道的作用。
Description
技术领域
本发明涉及生物医药技术领域，具体涉及Integrin/ROCK信号通路靶向调控剂在制备修复细胞骨架损伤修复药物的应用。
背景技术
在青光眼中，生理条件下引流约75％-80％房水的小梁网途径房水流出通道障碍起重要作用。房水动力学失调可能导致小梁网-Schlemm管异常灌注，使细胞骨架损伤继而出现营养及代谢障碍，功能受损，进一步增加房水流出通道阻力，眼压升高加剧,但增加房水外流的药物几乎都作用于葡萄膜巩膜途径，靶向小梁网途径的药物极其匮乏，目前尚无促进青光眼中小梁网细胞及Schlemm管内皮细胞骨架损伤后修复的药物，本专利拟修复小梁网途径房水流出通道中细胞骨架损伤。
发明内容
为了解决现有技术的缺陷与不足，本发明提供了一种Integrin/ROCK信号通路靶向调控剂在制备修复细胞骨架损伤修复药物的应用。
本发明采用的技术解决方案是：Integrin/ROCK信号通路靶向调控剂在制备修复细胞骨架损伤修复药物的应用。
所述的细胞骨架损伤为小梁网细胞骨架损伤。
所述的Integrin/ROCK信号通路靶向调控剂为二甲双胍。
所述的二甲双胍的浓度为3-10mM。
所述的小梁网细胞骨架损伤为青光眼中小梁网细胞氧化损伤引起的小梁网细胞骨架损伤。
二甲双胍在制备靶向修复小梁网细胞骨架损伤修复药物上的应用。
所述的药物包括二甲双胍口服制剂和眼药水制剂。
所述的眼药水制剂为0.3％或0.1％二甲双胍眼药水制剂。
所述的二甲双胍的浓度为3-10mM。
本发明的有益效果是：本发明提供了一种Integrin/ROCK信号通路靶向调控剂在制备修复细胞骨架损伤修复药物的应用，二甲双胍能通过调控 Integrin/ROCK信号通路促进细胞骨架损伤后重塑，抑制ROS释放，逆转细胞的氧化损伤，修复损伤后细胞骨架及形态的改变，减少房水流出通道中细胞外基质沉积，以达到保护房水流出通道的作用。
附图说明
图1为二甲双胍抑制HTMC(人小梁网细胞)增殖，逆转tBHP(叔丁基过氧化氢) 诱导的细胞形态改变。其中图1A为倒置相差荧光显微镜拍摄照片(20×)；
图1B为HTMC细胞活力呈二甲双胍浓度依赖性下降的示意图；图1C为tBHP联合二甲双胍作用后HTMC细胞活力改变示意图(MET：二甲双胍，药物浓度：mM， *代表p＜0.05；**代表p＜0.01)。
图2为二甲双胍逆转tBHP诱导的细胞骨架破坏并激活Intergin/ROCK信号通路。(倒置相差荧光显微镜拍摄照片，20×；MET：二甲双胍；药物浓度：mM)。
具体实施方式
下面将结合本发明实施例中的附图，对本发明实施例中的技术方案进行清楚、完整的描述，显然，所描述的实施例仅仅是本发明的一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其它实施例，都属于本发明保护的范围。
我们通过人小梁网细胞(human trabecular meshwork cells,HTMC)动物模型研究现二甲双胍通过调控Integrin/ROCK信号通路促进细胞骨架损伤的影响。
实施例
二甲双胍逆转tBHP导致的小梁网细胞骨架破坏
tBHP诱导的HTMC氧化损伤模型可见贴壁细胞排列紊乱，密度下降，部分细胞由梭形变钝圆，死亡细胞增多；而低浓度二甲双胍(3mM﹑5mM及10mM) 逆转了上述细胞形态改变，如图1所示，图1B显示HTMC细胞活力呈二甲双胍浓度依赖性下降；图1C显示tBHP联合二甲双胍作用后HTMC细胞活力改变。
如图2所示，二甲双胍逆转tBHP诱导的细胞骨架破坏并激Intergin/ROCK 信号通路。二甲双胍对正常HTMC细胞骨架无影响。tBHP作用HTMC后细胞质β-actin表达下降，而联用二甲双胍后β-actin表达呈浓度依赖性回升，伴细胞形态恢复。
结论
低浓度二甲双胍对正常HTMC肌动蛋白的标记物β-actin的表达无影响，但能恢复tBHP导致的β-actin表达下降，使细胞恢复规则。研究结果显示二甲双胍激活Integrin/ROCK信号通路。上述研究结果提示低浓度二甲双胍能通过激活Integrin/ROCK信号通路起到修复HTMC氧化损伤后细胞骨架及形态的改变的作用。
各位技术人员须知：虽然本发明已按照上述具体实施方式做了描述，但是本发明的发明思想并不仅限于此发明，任何运用本发明思想的改装，都将纳入本专利专利权保护范围内。
以上所述仅是本发明的优选实施方式，本发明的保护范围并不仅局限于上述实施例，凡属于本发明思路下的技术方案均属于本发明的保护范围。应当指出，对于本技术领域的普通技术人员来说，在不脱离本发明原理前提下的若干改进和润饰，这些改进和润饰也应视为本发明的保护范围。
Claims (9)
1.Integrin/ROCK信号通路靶向调控剂在制备修复细胞骨架损伤修复药物的应用。
2.根据权利要求1所述的应用，其特征在于，所述的细胞骨架损伤为小梁网细胞骨架损伤。
3.根据权利要求1所述的应用，其特征在于，所述的Integrin/ROCK信号通路靶向调控剂为二甲双胍。
4.根据权利要求3所述的应用，其特征在于，所述的二甲双胍的浓度为3-10mM。
5.根据权利要求2所述的应用，其特征在于，所述的小梁网细胞骨架损伤为青光眼中小梁网细胞氧化损伤引起的小梁网细胞骨架损伤。
6.二甲双胍在制备靶向修复小梁网细胞骨架损伤修复药物上的应用。
7.根据权利要求6所述的应用，其特征在于，所述的药物包括二甲双胍口服制剂和眼药水制剂。
8.根据权利要求6所述的应用，其特征在于，所述的眼药水制剂为0.3％或0.1％二甲双胍眼药水制剂。
9.根据权利要求6所述的应用，其特征在于，所述的二甲双胍的浓度为3-10mM。
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103834562A (zh) * | 2014-01-07 | 2014-06-04 | 中国人民解放军第三军医大学第二附属医院 | 离体眼前节组织培养装置 |
| CN109498620A (zh) * | 2018-12-18 | 2019-03-22 | 河南省立眼科医院（河南省眼科研究所） | 一种治疗青光眼的药物 |
| CN113368088A (zh) * | 2021-06-11 | 2021-09-10 | 上海交通大学医学院附属第九人民医院 | 二甲双胍在制备治疗眼部黑色素瘤的药物中的应用 |
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103834562A (zh) * | 2014-01-07 | 2014-06-04 | 中国人民解放军第三军医大学第二附属医院 | 离体眼前节组织培养装置 |
| CN109498620A (zh) * | 2018-12-18 | 2019-03-22 | 河南省立眼科医院（河南省眼科研究所） | 一种治疗青光眼的药物 |
| CN113368088A (zh) * | 2021-06-11 | 2021-09-10 | 上海交通大学医学院附属第九人民医院 | 二甲双胍在制备治疗眼部黑色素瘤的药物中的应用 |
Non-Patent Citations (1)
| Title |
|---|
| AMIN SV, KHANNA S, PARVAR SP, ET AL.: "《Metformin and retinal diseases in preclinical and clinical studies: Insights and review of literature》", 《EXPERIMENTAL BIOLOGY AND MEDICINE (MAYWOOD, N.J.)》, vol. 247, no. 4, pages 317 - 329 * |
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