CN116370450A - 化合物2-溴十六烷酸在治疗脑血管疾病中的应用 - Google Patents
化合物2-溴十六烷酸在治疗脑血管疾病中的应用 Download PDFInfo
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Abstract
本发明公开了化合物2‑溴十六烷酸在治疗脑血管疾病中的应用。本发明首次公开了2‑BP能明显减少局灶性缺血性脑卒中小鼠急性期脑梗死体积、显著改善其神经行为学症状、抑制反应性星形胶质细胞增生，具有脑神经保护作用。2‑BP可以作为一种有前景的治疗脑血管疾病的药物。
Description
技术领域
本发明属于药物应用技术，具体涉及化合物2-溴十六烷酸在治疗脑血管疾病中的应用。
背景技术
脑卒中是一组以脑组织缺血及出血性损伤症状为主要临床表现的疾病，又称脑中风或脑血管意外。该病发病急，有极高的致残率和致死率，是当今世界导致死亡的第二大病因，且随着人口老龄化变得越来越严重。急性缺血性脑卒中（急性脑梗死）是最常见的卒中类型，缺血性脑卒中的发病机制复杂，涉及过氧化、能量代谢障碍、钙超载、兴奋性氨基酸毒性等多种机制。目前唯一被美国FDA批准用于缺血性脑卒中治疗的药物是组织型纤维酶原激活剂（tissue plasminogen activator, t-PA，静脉注射），它可以溶解血栓，使血管再通，从而恢复血流。但由于组织型纤维酶原激活剂( t-PA)的治疗窗较窄（卒中后4.5小时使用有效）及易引起出血，仅有小部分患者得到溶栓治疗。因此，寻找治疗缺血性脑卒中新的靶点，具有新作用机制、不良反应少的药物是一件急需解决的问题。
发明内容
2-溴十六烷酸（2-Bromopalmitate ，2-BP)可以逆转脊髓星形胶质细胞线粒体融合和裂变动态失衡来减轻骨癌症疼痛，可以抑制T细胞活化，使其成为治疗自身免疫性疾病的潜在免疫抑制剂。但2-BP是否在缺血性脑卒中等脑血管疾病中具有保护作用尚未见文献报道。
本发明公开了化合物2-溴十六烷酸在制备治疗脑血管疾病药物中的应用。
2-BP能明显减少局灶性脑缺血小鼠急性期脑梗死体积、显著改善其神经症状、抑制反应性星形胶质细胞增生，具有脑神经保护作用，说明2-BP可以用于治疗缺血性脑卒中。因此，本发明公开了化合物2-溴十六烷酸在制备减少脑梗死体积药物、改善脑缺血神经症状药物、抑制反应性星形胶质细胞增生药物、治疗缺血性脑卒中药物中的应用。
本发明首次公开了2-BP能明显减少局灶性缺血性脑卒中小鼠急性期脑梗死体积、显著改善其神经行为学症状、抑制反应性星形胶质细胞增生，具有脑神经保护作用。2-BP可以作为一种有前景的治疗脑血管疾病的药物。
附图说明
图1为化合物2-BP对于减少脑缺血小鼠急性期的脑梗死体积的影响示意图。
图2为化合物2-BP对改善脑缺血小鼠的神经症状的影响示意图。
图3为化合物2-BP对棕榈酰化转移酶ZDHHC5和反应性星形胶质细胞GFAP的影响示意图。
图4为化合物2-BP对于氧糖剥夺再复氧星形胶质细胞保护作用示意图。
图5为化合物2-BP对于抑制反应性星形胶质细胞增生示意图。
具体实施方式
本发明公开了2-BP具有治疗缺血性脑卒中的作用，为缺血性脑卒中等脑血管疾病的药物研发提供新靶点、新作用机制及新思路。本发明采用的原料为现有产品，具体实验操作以及测试为常规技术。
实施例一
雄性C57小鼠，随机分为正常对照组（sham）、模型组（I/R）、给药组(I/R+2-BP)，每组10只。采用常规线栓法制作小鼠短暂性大脑中动脉闭塞模型（tMCAO）。缺血60 min后再灌注，再灌注时立即尾静脉注射2-BP（40mg/kg）。将小鼠断头取脑并切片TTC染色观察2-BP对脑缺血急性期脑梗死体积的影响。在处死小鼠前采用Longa法对再灌注后（I/R）的小鼠进行脑缺血急性期的神经症状评分，评分越高，神经功能缺陷越明显。如表1所示为神经症状评分标准。
图1为化合物2-BP对改善脑缺血小鼠的神经症状的影响示意图；mean±SD，n=10；与模型组比较，***p<0.001。由图2可知：化合物2-BP能够减少脑缺血小鼠的神经症状评分。
图2为化合物2-BP对于减少脑缺血小鼠急性期的脑梗死体积的影响示意图；mean±SD，n=10；与模型组比较，****p<0.0001。由图1可知：化合物2-BP能够减少脑缺血小鼠急性期的脑梗死体积。
图3为化合物2-BP对反应性星形胶质细胞GFAP的影响示意图；mean ± SD，n=5；与模型组比较，**p<0.01，****p<0.0001。由图3可知：化合物2-BP能够抑制反应性星形胶质细胞GFAP的表达。
图4为化合物2-BP对于氧糖剥夺再复氧星形胶质细胞保护作用示意图；与模型组比较，**p<0.01。由图4可知：化合物2-BP以剂量依赖的方式改善细胞活力。
图5为化合物2-BP对于抑制反应性星形胶质细胞增生示意图。由图5可知：化合物2-BP能够抑制反应性星形胶质细胞增生。
以上结果表明：2-BP对缺血性脑损伤具有一定的保护作用，可以用于这一类脑血管疾病的预防和治疗。
本发明首次公开了2-BP能明显减少局灶性脑缺血小鼠急性期脑梗死体积、显著改善其神经症状、抑制反应性星形胶质细胞增生，具有脑神经保护作用。说明2-BP可以作为一种有前景的治疗缺血性脑卒中等脑血管疾病的药物。
Claims (10)
1.化合物2-溴十六烷酸在制备治疗脑血管疾病药物中的应用。
2.化合物2-溴十六烷酸在制备减少脑梗死体积药物中的应用。
3.化合物2-溴十六烷酸在制备改善脑缺血神经症状药物中的应用。
4.化合物2-溴十六烷酸在制备抑制反应性星形胶质细胞增生药物中的应用。
5.化合物2-溴十六烷酸在制备治疗缺血性脑卒中药物中的应用。
6.根据权利要求1至5任意一项所述的应用，其特征在于，药物的活性成分为2-溴十六烷酸。
7.根据权利要求1至5任意一项所述的应用，其特征在于，药物为注射药物或者口服药物。
8.一种治疗脑血管疾病的药物，其特征在于，活性成分为2-溴十六烷酸。
9.根据权利要求8所述治疗脑血管疾病的药物，其特征在于，药物为注射药物或者口服药物。
10.根据权利要求8所述治疗脑血管疾病的药物，其特征在于，脑血管疾病包括缺血性脑卒中。
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