Z-没药甾酮对急性血瘀模型大鼠凝血和血管内皮功能的改善作用及其机制研究
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篇名: Z-没药甾酮对急性血瘀模型大鼠凝血和血管内皮功能的改善作用及其机制研究
TITLE:
摘要: 目的:研究Z-没药甾酮(Z-GL)对急性血瘀模型大鼠凝血和血管内皮功能的改善作用及其机制。方法:将40只大鼠随机分为正常组、模型组、阳性组(阿司匹林片,50 mg/kg)和Z-GL低、高剂量组(25、50 mg/kg),每组8只,各给药组大鼠每12 h ig相应药物1次,正常组和模型组大鼠ig生理盐水,连续给药7次。第5次给药后,除正常组外其余各组大鼠ih盐酸肾上腺素+冰水刺激复制急性血瘀模型。给药结束后30 min内,取腹主动脉血检测凝血指标[凝血酶原时间(PT)、凝血酶时间(TT)、活化部分凝血活酶时间(APTT)、纤维蛋白原(FIB)],并取大鼠颈动脉观察其病理变化。将人脐静脉血管内皮细胞(HUVECs)分为空白组(生理盐水)、模型组(生理盐水)和Z-GL低、高浓度组(25、50 μmol/L),培养24 h后,对模型组和Z-GL组细胞进行氧糖剥夺6 h,检测细胞中磷酸化内皮型一氧化氮合成酶(p-eNOS)蛋白表达水平;另取细胞,分组、给药、处理方式同上,检测细胞中一氧化氮(NO)水平。结果:与正常组比较,模型组大鼠PT、TT、APTT缩短,FIB含量增加(P<0.01),颈动脉内皮受损、血管内皮细胞部分从血管壁脱落;与模型组比较,各给药组大鼠TT、PT、APTT延长,FIB含量减少(P<0.05或P<0.01),血管内皮受损程度减轻。p-eNOS蛋白及NO检测结果显示,与模型组比较,Z-GL给药组细胞中p-eNOS蛋白表达及NO水平升高(P<0.05或P<0.01)。结论:Z-GL能有效改善血瘀模型大鼠凝血和血管内皮功能,其机制可能与其激活eNOS、升高细胞内NO水平有关。
ABSTRACT: OBJECTIVE: To study the improvement effect of Z-Guggulsterone (Z-GL) on blood coagulation and vascular endothelial functions of acute blood-stasis model rats and its mechanism. METHODS: 40 rats were randomly divided into normal group, model group, positive group (Aspirin tablet, 50 mg/kg) and Z-GL low-dose and high-dose groups (25, 50 mg/kg), with 8 rats in each group. They were given relevant medicine intragastrically every 12 h, and normal group and model group were given constant volume of normal saline intragastrically for consecutive 7 times. After the fifth administration, except for normal group, those groups were given adrenalin hydrochloride subcutaneously+ice-cold water to induce acute blood-stasis model. Within 30 min after the last administration, aorta abdominalis sample were selected to detect the coagulation parameters [prothrombin time (PT), thrombin time (TT), activated partialthromboplastin time (APTT), fibrinogen (FIB)], and pathological changes of carotid artery were observed. Human umbilical vein endothelial cells (HUEVCs) were divided into blank group (normal saline), model group (normal saline) and Z-GL low-concentration and high-concentration groups (25, 50 μmol/L). After culturing for 24 h, the cells were exposed to glucose and oxygen deprivation for 6 h in model group and Z-GL groups. The expression of p-eNOS protein was detected. Other cells were selected, grouped, administrated and treated as above cells, and the NO level of these cells were detected. RESULTS: Compared with normal group, PT, TT and APTT were all shortened in model group, while FIB content was increased (P<0.01); vascular endothelium was injured, and endothelial cells fell off from the wall. Compared with model group, PT, TT and APTT were prolonged in administration groups, while FIB content was decreased (P<0.05 or P<0.01); vascular endothelium injury was relieved. Results of p-eNOS protein and NO levels determination showed that compared with model group, p-eNOS protein and NO levels were increased in Z-GL groups (P<0.05 or P<0.01). CONCLUSIONS: Z-GL can significantly improve coagulation and vascular endothelium functions of blood-stasis model rats, and its mechanism may be associated with the activation of eNOS and the increase of NO level.
期刊: 2016年第27卷第19期
作者: 李宏力,李玉文,刘天龙,文爱东
AUTHORS: LI Hongli,LI Yuwen,LIU Tianlong,WEN Aidong
关键字: Z-没药甾酮;血瘀证;凝血功能;血管内皮功能;内皮型一氧化氮合成酶;大鼠;人脐静脉血管内皮细胞
KEYWORDS: Z-Guggulsterone; Blood-stasis; Coagulation function; Vascular endothelium functions; eNOS; Rat; Human umbilical vein endothelial cells
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