Sun Qian, Shi Pengqiang, Lin Cuiling, Ma Jing
Department of Neurology, Xinxiang Central Hospital, Xinxiang, China.
Department of Neurosurgery, Xinxiang Central Hospital, Xinxiang, China.
Front Bioeng Biotechnol. 2020 Dec 23;8:616759. doi: 10.3389/fbioe.2020.616759. eCollection 2020.
To investigate the efficacy and improvement of Astragalus polysaccharides (APS) and APS-nano on cerebral thrombosis in rats.
A total of 72 SD rats were randomly divided into NC group, Model group, APS-Nano group, and APS group. The cerebral thrombosis Model of SD rats was established by injecting compound thrombus inducer into the internal carotid artery. After 14 days of different intervention treatments, the TTC staining of brain tissue were performed, and A/left brain wet weight ratio, left brain/right brain wet weight ratio, blood rheology indexes, and coagulation function indexes of cerebral thrombosis were measured. ELISA was used to measure the contents of thromboxane 2 (TXB2), 6-keto-prostaglandin F1α (6-Keto-PGF1α), tissue factor (TF), neuron-specific enolase (NSE), S-100β, catenin (CAT), superoxide dismutase (SOD), as well as malondialdehyde (MDA). The binding specificity between miR-885-3p and TF was verified by the double-luciferin reporting experiment, and western blot was used to measure the expression level of TF protein.
Compared with the Model group, after treatment with APS-nano or APS, the ratio of left brain/right brain wet weight decreased significantly. Whole blood low shear viscosity (WBLSV), whole blood high shear viscosity (WBHSV), plasma viscosity (PV), and erythrocyte aggregation index (Arbc) was all reduced. In addition, prothrombin time (PT) and activated partial thromboplastin time (APTT) were increased, and fibrinogen (FIB) content was decreased. The expression of TXB2, 6-Keto-PGF1α, and TF showed a downward trend. Similarly, the expression of TF protein was decreased. Furthermore, the contents of NSE and S-100β proteins were all decreased, whereas the contents of CAT and SOD were increased, and the contents of MDA was decreased. At the same dose, compared with APS treatment, APS-nano treatment had a significant inhibitory effect on cerebral thrombosis in rats. Finally, we found that TF is a target gene of miR-885-3p and specifically binds to miR-885-3p.
APS has a significant inhibitory effect on the formation of cerebral thrombosis induced by compound thrombus inducers. Moreover, APS-nano has a more significant inhibitory effect on cerebral thrombosis. Meanwhile, the regulation of miR-885-3p regulating TF expression may be related to the occurrence of cerebral thrombosis.
探讨黄芪多糖（APS）及纳米黄芪多糖（APS - nano）对大鼠脑血栓形成的影响及改善作用。
将72只SD大鼠随机分为正常对照组（NC组）、模型组、APS - Nano组和APS组。通过向颈内动脉注射复方血栓诱导剂建立SD大鼠脑血栓模型。经过14天不同干预处理后，对脑组织进行TTC染色，测量脑血栓的A/左脑湿重比、左脑/右脑湿重比、血液流变学指标及凝血功能指标。采用ELISA法检测血栓素2（TXB2）、6 - 酮 - 前列腺素F1α（6 - Keto - PGF1α）、组织因子（TF）、神经元特异性烯醇化酶（NSE）、S - 100β、连环蛋白（CAT）、超氧化物歧化酶（SOD）以及丙二醛（MDA）的含量。通过双荧光素报告实验验证miR - 885 - 3p与TF之间的结合特异性，采用蛋白质免疫印迹法检测TF蛋白的表达水平。
与模型组相比，经APS - nano或APS处理后，左脑/右脑湿重比显著降低。全血低切黏度（WBLSV）、全血高切黏度（WBHSV）、血浆黏度（PV）及红细胞聚集指数（Arbc）均降低。此外，凝血酶原时间（PT）和活化部分凝血活酶时间（APTT）延长，纤维蛋白原（FIB）含量降低。TXB2、6 - Keto - PGF1α及TF的表达呈下降趋势。同样，TF蛋白表达降低。此外，NSE和S - 100β蛋白含量均降低，而CAT和SOD含量升高，MDA含量降低。在相同剂量下，与APS处理相比，APS - nano处理对大鼠脑血栓形成具有显著抑制作用。最后，我们发现TF是miR - 885 - 3p的靶基因，且能与miR - 885 - 3p特异性结合。
APS对复方血栓诱导剂所致大鼠脑血栓形成具有显著抑制作用。此外，APS - nano对脑血栓形成的抑制作用更显著。同时，miR - 885 - 3p调控TF表达可能与脑血栓的发生有关。
