注射用丹参多酚酸对角叉菜胶诱导的慢性尾部血栓小鼠的抗炎性血栓作用研究  

Anti-thrombus effect of Salvianolic Acid for Injection on chronic tail thrombosis induced by carrageenan in mice

作　　者：原景 万梅绪[1,2] 张燕欣 李智 庄朋伟 李德坤[1,2] 鞠爱春[1,2] YUAN Jing;WAN Meixu;ZHANG Yanxin;LI Zhi;ZHUANG Pengwei;LI Dekun;JU Aichun(Tianjin Tasly Pride Pharmaceutical Co.,Ltd.,Tianjin 300410,China;Tianjin Key Laboratory of Safety Evaluation Enterprise of TCM Injections,Tianjin 300410,China;Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China)

机构地区：[1]天津天士力之骄药业有限公司,天津300410 [2]天津市中药注射剂安全性评价企业重点实验室,天津300410 [3]天津中医药大学,天津301617

出　　处：《药物评价研究》2023年第8期1659-1664,共6页Drug Evaluation Research

摘　　要：目的通过ip角叉菜胶(Ca)溶液建立小鼠慢性尾部血栓模型,尾iv给予注射用丹参多酚酸(SAFI),探究其抗炎症血栓作用。方法将168只KM雄性小鼠随机分为6组:对照组,模型组,SAFI低、中、高剂量(8.365、16.730、33.460 mg·kg^(-1))组,造模同时给药组(即造模的同时予以SAFI给药,其余组于造模后给药,16.730 mg·kg^(-1))。连续4 d ip 0.06%Ca(10 mL·kg^(-1))制备血栓模型,4 d后,对照组和模型组尾iv 0.9%氯化钠注射液,其余各组分别尾iv相应剂量的SAFI,每天1次,给药7 d。给药开始后每天记录各组小鼠的出栓情况;给药结束后各组小鼠摘眼球取血,试剂盒法检测血清中6-酮-前列腺素F1α(6-keto-PGF1α)、血栓素B2(TXB2)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)水平,取尾部组织进行病理切片,HE染色观察组织损伤。结果模型组小鼠出栓率随时间延长增加,在给药第5天出栓率达到100%;SAFI各剂量组小鼠出栓率均低于同一天的模型组,且低、中、高剂量组小鼠出栓率结果存在一定的剂量相关性;造模同时给药组出栓率均低于同一天的模型组,且相比于同一剂量(中剂量组)出栓率更低。与模型组比较,SAFI中、高剂量组和造模同时给药组血清中TXB2水平显著降低(P<0.05、0.01、0.001),6-keto-PGF1α水平显著升高(P<0.01、0.001);SAFI低剂量组小鼠血清IL-6水平显著降低(P<0.05),中、高剂量组和造模同时给药组小鼠血清TNF-α、IL-1β、IL-6水平显著降低(P<0.05、0.01、0.001);SAFI高剂量组、造模同时给药组血栓情况均明显改善。结论ip 0.06%Ca制备的炎症血栓小鼠模型稳定、可靠,SAFI能改善炎症血栓小鼠血清中6-keto-PGF1α、TXB2、IL-6、IL-1β、TNF-α水平,有效缓解炎性因子导致的血栓症状。Objective Chronic thrombus model was established by ip injection of carrageenan(Ca)solution in mice,and then Salvianolic Acid for Injection(SAFI)was given to investigate its anti-inflammatory thrombus effect.Methods 168 KM male mice were randomly divided into seven groups:Control group,model group,SAFI low,medium,and high-dose(8.365,16.730,and 33.460 mg·kg^(-1))group,model making and drug administration group(i.e.model making and drug administration were conducted simultaneously,while the other groups were administered after model making,16.730 mg·kg^(-1)).The thrombus model was prepared by ip 0.06%Ca for four consecutive days.After four days,the corresponding dose of SAFI was administered to the other groups,except for the control group and the model group iv 0.9%sodium chloride injection.The thrombolysis of each group of mice was recorded every day after the beginning of administration.Blood was removed from the eyeballs of each group and 6-ketoprostaglandin1α(6-keto-PGF1α),thromboxane(TXB2),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),interleukin-1β(IL-1β)levels in serum were detected by kits.After the experiment,the tail tissue was taken for pathological section,and the tissue damage was observed by HE staining.Results The incidence of thrombosis in the model group increased with time,reaching 100%on the 5th day of administration.The incidence of thrombosis in mice of each dose group of SAFI was lower than that of the model group on the same day,and there was a certain dose correlation between the incidence of thrombosis in mice of low,medium,and high dose groups.The incidence of thrombosis in the simultaneous administration group was lower than that in the model group on the same day,and lower compared to the same dose(medium dose group).Compared with the model group,the serum TXB2 levels in the SAFI medium and high dose groups,as well as the simultaneous administration of models,were significantly reduced(P<0.05,0.01,0.001),with the level of 6-keto-PGF1αsignificantly increased(P<0.01,0.001).T

关 键 词：注射用丹参多酚酸 角叉菜胶 炎症 血栓 血栓素B2 白细胞介素-6 肿瘤坏死因子-Α 

分 类 号：R285.5[医药卫生—中药学]