琥珀酸脱氢表鬼臼酯的抗血栓作用：和研究。

The antithrombosis effect of dehydroandrographolide succinate: and studies.

机构信息

Clinical Laboratory, Jiangxi Provincial People's Hospital Affiliated to Nanchang University, Nanchang, China.

Jiangxi Cardiovascular Research Institute, Jiangxi Provincial People's Hospital Affiliated to Nanchang University, Nanchang, China.

出版信息

Pharm Biol. 2022 Dec;60(1):175-184. doi: 10.1080/13880209.2021.2021948.

DOI:10.1080/13880209.2021.2021948

PMID:35014931

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8757605/

Abstract

CONTEXT

Dehydroandrographolide succinate (DAS) is mainly used in the clinical treatment of various infectious diseases. Its potential effects on platelet aggregation and blood coagulation systems have not been reported systematically.

OBJECTIVE

To explore whether DAS exerts an antithrombotic effect and its internal mechanism.

MATERIALS AND METHODS

Human blood samples and Sprague-Dawley (SD) rats divided into control, aspirin (30 mg/kg), and DAS groups (200, 400 and 600 mg/kg) were used to measure the platelet aggregation rate, coagulation function, coagulation factor activity, and contents of thromboxane B (TXB) and 6-keto-prostaglandin F (6-keto-PGF). The histopathology of the SD rat gastric mucosa was also observed. All rats were administered intragastric or intraperitoneal injections once a day for 3 consecutive days.

RESULTS

Compared to control group, DAS significantly inhibited the platelet aggregation rate (ED = 386.9 mg/kg) by decreasing TXB levels (1531.95 ± 649.90 pg/mL to 511.08 ± 411.82 pg/mL) and activating antithrombin III (AT-III) (103.22 ± 16.22% to 146.46 ± 8.96%) ( < 0.05). In addition, DAS significantly enhanced the coagulation factors FV (304.12 ± 79.65% to 443.44 ± 75.04%), FVII (324.19 ± 48.03% to 790.66 ± 225.56%), FVIII (524.79 ± 115.47% to 679.92 ± 143.34%), FX (34.90 ± 7.40% to 102.76 ± 29.41%) and FXI (38.12 ± 10.33% to 65.47 ± 34.08%), increased the content of Fg (2.18 ± 0.39 to 3.61 ± 0.37 g/L), shorten the PT (10.42 ± 0.44 to 9.22 ± 0.21 s), APTT (16.43 ± 1.4 to 14.07 ± 0.75 s) and TT time (37.04 ± 2.13 to 32.68 ± 1.29 s) ( < 0.05), while the aspirin group showed no such effect on these items but showed reduced activity of FII (89.21 ± 21.72% to 61.83 ± 8.95%) and FVIII (524.79 ± 115.47% to 306.60 ± 29.96%) ( < 0.05). Histopathological changes showed aspirin-induced gastric mucosa haemorrhage and the protective effect of DAS in the gastric mucosa.

CONCLUSIONS

DAS is more suitable than aspirin in thromboprophylaxis treatment, which provides a reliable theoretical and experimental basis for its clinical application.

摘要

背景

琥珀酸脱氢表雄酮（DAS）主要用于各种传染病的临床治疗。其对血小板聚集和凝血系统的潜在影响尚未系统报道。

目的

探讨 DAS 是否具有抗血栓作用及其内在机制。

材料和方法

使用人血样本和 Sprague-Dawley（SD）大鼠分为对照组、阿司匹林（30mg/kg）组和 DAS 组（200、400 和 600mg/kg），测量血小板聚集率、凝血功能、凝血因子活性、血栓素 B（TXB）和 6-酮-前列腺素 F（6-keto-PGF）含量。还观察了 SD 大鼠胃黏膜的组织病理学。所有大鼠连续 3 天每天分别进行灌胃或腹腔注射。

结果

与对照组相比，DAS 通过降低 TXB 水平（从 1531.95±649.90pg/mL 降至 511.08±411.82pg/mL）和激活抗凝血酶 III（AT-III）（从 103.22±16.22%降至 146.46±8.96%）（<0.05）显著抑制血小板聚集率（ED=386.9mg/kg）。此外，DAS 还显著增强了凝血因子 FV（从 304.12±79.65%增加到 443.44±75.04%）、FVII（从 324.19±48.03%增加到 790.66±225.56%）、FVIII（从 524.79±115.47%增加到 679.92±143.34%）、FX（从 34.90±7.40%增加到 102.76±29.41%）和 FXI（从 38.12±10.33%增加到 65.47±34.08%），增加了纤维蛋白原（Fg）的含量（从 2.18±0.39g/L 增加到 3.61±0.37g/L），缩短了 PT（从 10.42±0.44s 减少到 9.22±0.21s）、APTT（从 16.43±1.4s 减少到 14.07±0.75s）和 TT 时间（从 37.04±2.13s 减少到 32.68±1.29s）（<0.05），而阿司匹林组在这些项目上没有表现出这种效果，但 FII（从 89.21±21.72%减少到 61.83±8.95%）和 FVIII（从 524.79±115.47%减少到 306.60±29.96%）的活性降低（<0.05）。组织病理学变化显示阿司匹林引起的胃黏膜出血和 DAS 对胃黏膜的保护作用。