来匹卢定对大鼠急性肺栓塞的作用研究  

Effects of lepirudine on acute pulmonary embolism in rats

作　　者：胡聪龙 伍晨 肖莎莎 刘轶群 HU Cong-long;WU Chen;XIAO Sha-sha;LIU Yi-qun(Emergency Medicine,Hunan Provincial People's Hospital/The First Affiliated Hospital of Hunan Normal University,Changshaa410000,Hunan Province,China)

机构地区：[1]湖南省人民医院、湖南师范大学附属第一医院急诊医学科,湖南长沙410000

出　　处：《中国临床药理学杂志》2024年第18期2719-2723,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的探讨来匹卢定通过调控Notch信号通路抑制血小板聚集治疗急性肺栓塞的作用机制。方法将SD大鼠随机分为假手术组、模型组和实验组,每组10只。模型组和实验组大鼠用自体血栓法建立急性肺栓塞模型。实验组于造模前24、0.5h以及造模后24h腹腔注射2.0mg·kg^(-1)来匹卢定,假手术组、模型组在相同时间点腹腔注射等体积0.9%NaCl。用酶联免疫吸附法检测大鼠血浆中血小板P选择素62(CD62P)、血小板颗粒膜蛋白-140(GMP-140)、N-末端脑钠肽前体(NT-proBNP)和肌钙蛋白T(cTnT)含量,用RIA法检测大鼠血浆中血栓素B2(TXA2)和前列环素(PGI2)含量,用蛋白质印迹法检测大鼠肺组织中Notch受体蛋白1(Notch1)和Notch配体蛋白1(JAGGED1)的蛋白相对表达水平。结果假手术组、模型组和实验组大鼠血浆中CD62P含量分别为(9.31±1.31)、(25.03±2.66)和(11.42±2.21)ng·mL^(-1),GMP-140含量分别为(43.23±5.61)、(114.33±14.02)和(73.44±6.97)ng·mL^(-1),NT-proBNP含量分别为(14.71±1.93)、(20.57±3.46)和(11.07±3.06)ng·mL^(-1),cTnT含量分别为(81.07±9.77)、(233.24±27.61)和(134.76±15.00)pg·mL^(-1),TXA2含量分别为(231.06±17.33)、(378.69±29.10)和(268.61±24.15)pg·mL^(-1),PGI2含量分别为(147.25±16.44)、(104.37±11.62)和(136.09±13.40)pg·mL^(-1),肺组织中Notch1蛋白相对表达水平分别为1.24±0.21、0.51±0.06和0.87±0.09,JAGGED1蛋白相对表达水平分别为1.02±0.15、0.17±0.02和0.28±0.06。模型组的上述指标与假手术组和实验组相比,在统计学上差异均有统计学意义(P<0.01,P<0.001)。结论来匹卢定可能通过激活Notch信号通路抑制血小板聚集治疗急性肺栓塞。Objective To explore the mechanism of lepirudine in inhibiting thrombin activation by regulating the Notch signaling pathway for the treatment of acute pulmonary embolism.Methods SD rats were randomly divided into sham group,model group and experimental group,with 10 rats in each group.Acute pulmonary embolism model was established by autologous thrombosis in model group and experimental group.Experimental group was intraperitoneally injected with lepiludine(2.0 mg·kg^(-1))at 24 h,0.5 h before and 24 h after modeling,respectively,while sham group and model group were intraperitoneally injected with 0.9%NaCl at the same time point.The contents of platelet P-selectin 62(CD62P),platelet granule membrane protein-140(GMP-140),N-terminal pro-brain natriuretic peptide(NT-proBNP)and cardiac troponin T(cTnT)in rat plasma were detected by enzyme-linked immunosorbent assay(ELISA).The contents of thromboxane B2(TXA2)and prostacyclin(PGI2)in rat plasma were detected by RIA.The protein expression levels of Notch receptor protein 1(Notch1)and Notch ligand protein 1(JAGGED1)in lung tissue of rats were detected by Western blot.Results The plasma CD62P content in sham group,model group and experimental group were(9.31±1.31),(25.03±2.66)and(11.42±2.21)ng·mL^(-1);the contents of GMP-140 were(43.23±5.61),(114.33±14.02)and(73.44±6.97)ng·mL^(-1);the contents of NT-proBNP were(14.71±1.93),(20.57±3.46)and(11.07±3.06)ng·mL^(-1);cTnT content were(81.07±9.77),(233.24±27.61)and(134.76±15.00)pg·mL^(-1);TXA2content were(231.06±17.33),(378.69±29.10)and(268.61±24.15)pg·mL^(-1);PGI2content were(147.25±16.44),(104.37±11.62)and(136.09±13.40)pg·mL^(-1);the relative expression levels of Notch1protein in lung tissue were 1.24±0.21,0.51±0.06 and 0.87±0.09;the relative expression levels of JAGGED1protein were 1.02±0.15,0.17±0.02 and 0.28±0.06.Compared with sham group and experimental group,there were statistically significant differences in the above indexes in model group(P<0.01,P<0.001).Conclusion Lepirudine can inhibit

关 键 词：来匹卢定 重组水蛭素 急性肺栓塞 NOTCH信号通路 血小板活化 血小板聚集 

分 类 号：R974[医药卫生—药品]