中药复方对心房颤动大鼠血清...-α和ICAM-1水平影响_史富羽.pdf

25第 2 5 卷 第 1 期 2023 年 1 月辽 宁 中 医 药 大 学 学 报JOURNAL OF LIAONING UNIVERSITY OF TCMVol.25 No.1 Jan.，2023中药复方对心房颤动大鼠血清中TNF-和ICAM-1水平影响史富羽1，宫丽鸿2，吴启华1，韩乔木1，赵帅1，肖福龙2（1.辽宁中医药大学，辽宁 沈阳 110847；2.辽宁中医药大学附属医院，辽宁 沈阳 110032）基金项目：辽宁特聘教授项目（辽教函 2018 35号）作者简介：史富羽（1996-），女，辽宁鞍山人，硕士在读，研究方向：中西医结合防治心血管疾病。通讯作者：宫丽鸿（1970-），女，辽宁沈阳人，教授、主任医师，博士研究生导师，博士后，研究方向：中西医结合防治心血管疾病。E-mail：。摘要：目的 研究中药复方对心房颤动大鼠血清中肿瘤坏死因子-（TNF-）和细胞间黏附分子1（ICAM-1）水平的影响，探讨中药复方防治房颤的可能机制。方法 60只雄性SD大鼠随机分为空白组（10只）和造模组（50只）两组，模型组连续7 d采用尾静脉注射乙酰胆碱合并氯化钙Ach（66 g/mL）-CaCl2（10 mg/mL）混合液的方式建立心房颤动大鼠模型。将造模成功的大鼠用随机数字表法分为模型组、中药复方高剂量组、中药复方中剂量组、中药复方低剂量组和维拉帕米组共5组，连续灌胃2周，期间仍保持尾静脉注射。2周后使用多导生理记录仪15T（PowerLab 15T）数据采集与分析系统记录肢体导联心电图，监测各组大鼠房颤的持续时间；采用苏木精-伊红（HE）染色观察大鼠心房肌组织病理形态表现；酶联免疫吸附法（ELISA）检测大鼠血清中TNF-、ICAM-1的表达水平。结果（1）HE染色结果显示，空白组大鼠心房肌组织染色均匀，细胞形态正常；模型组大鼠心房肌细胞肿胀，纤维组织排列紊乱、断裂；与模型组相比，中药复方高剂量组、中药复方中剂量组及维拉帕米组鼠心房肌细胞肿胀改善，心房肌纤维排列相对整齐。（2）与空白组相比，模型组大鼠血清中TNF-和ICAM-1水平升高（P0.01）。与模型组相比，中药复方高剂量组、中药复方中剂量组、中药复方低剂量组和维拉帕米组大鼠血清中TNF-水平降低（P0.05或P0.01）；中药复方高剂量组、中药复方中剂量组和维拉帕米组ICAM-1水平降低（P0.05 or P0.01）。结论 中药复方可以降低血清中TNF-和ICAM1水平，抑制炎症因子的过度表达，减轻心脏炎症活动度，改善心房肌组织损伤，从而发挥对心房颤动的治疗作用。关键词：心房颤动；中药复方；炎症反应；肿瘤坏死因子；细胞间黏附分子中图分类号：R541.75 文献标志码：A 文章编号：1673-842X (2023)01-0025-05Effects of Traditional Chinese Medicine Compound on Serum Levels of TNF-and ICAM-1 in Atrial Fibrillation RatsSHI Fuyu1，GONG Lihong2，WU Qihua1，HAN Qiaomu1，ZHAO Shuai1，XIAO Fulong2（1.Liaoning University of Traditional Chinese Medicine，Shenyang 110847，Liaoning，China；2.Affiliated 2 MIAO EA，LEAF IA，TREUTINGP M，et al.Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria J .Nature Immunology，2010，11(12 )：1136-1142.3 GUO H，CALLAWAY JB，TING P Y.Inflammasomes：mechanism of action，role in disease，and therapeutics J .Nature Medicine，2015，21(7 )：677-687.4 DEMPSEY C，RUBIO ARAIZ A，BRYSON KJ，et al.Inhibiting the NLRP3 inflammasome with MCC950 promotes non-phlogistic clearance of amyloid-and cognitive function in APP/PS1 mice J .Brain Behavior&Immunity，2017，61：306-316.5 LU Y，XIAO G，LUO W.Minocycline suppresses NLRP3 inflammasome activation in experimental ischemic stroke J .Neuroimmunomodulation，2016，23(4 )：230-238.6 FAN Y X，DU L W，FU Q，et al.Inhibiting the NLRP3 inflammasome with MCC950 ameliorates isoflurane-induced pyroptosis and cognitive impairment in aged mice J .Front Cell Neurosci，2018，12：426.7 HAN C，YANG Y，GUAN Q，et al.New mechanism of nerve injury in Alzheimers disease：-amyloid-induced neuronal pyroptosis J .Cell Mol Med，2020，24(14 )：8078-8090.8 QI Y，JI X F，CHI T Y，et al.Xanthoceraside attenuates amyloid peptide1-42-induced memory impairments by reducing neuroinflammatory responses in mice J .Eur J Pharmacol，2018，820：18-30.9 齐越，李荧，贾冬，等.癫痫清颗粒对阿尔茨海默病小鼠学习记忆能力的影响和作用机制研究 J .中国现代医生，2021，59(32 )：34-40.10 YAND Y，WAND H，KOUADIR M，et al.Recent advances in the mechanisms of NLRP3 inflammasome activation and its inhibitors J .Cell Death Dis，2019，10(2 )：128.11 YUN Z，ZHIFANG D，WEIHONG S.NLRP3 inflammasome as a novel therapeutic target for Alzheimers disease J .Signal Transduct Target Ther，2020，5(1 )：2.12 HENEKA MT，KUMMER MP，STUTZ A，et al.NLRP3 is activated in Alzheimers disease and contributes to pathology in APP/PS1 mice J .Nature，2013，493(7434 )：674-678.13 COUTURIER J，STANCU IC，SCHAKMAN O，et al.Activation of phagocytic activity in astrocytes by reduced expression of the inflammasome component ASC and its implication in a mouse model of Alzheimer disease J .Neuroinflammation，2016，13(1 )：20.14 COLL RC，HILL JR，DAY CJ.MCC950 directly targets the NLRP3 ATP-hydrolysis motif for inflammasome inhibition J .Nat Chem Biol，2019，15(6 )：1.15 CORCORAN SE，HALAI R，COOPER MA.Pharmacological inhibition of the nod-like receptor family pyrin domain containing 3 inflammasome with MCC950 J .Pharmacol Rev，2021，73(3 )：968-1000.16 FEKETE C，VASTAGH C，DENES A，et al.Chronic amyloid oligomer infusion evokes sustained inflammation and microglial changes in the rat Hippocampus via NLRP3 J .Neurosci，2019，405：35-46.17 GUSTIN A，KIRCHMEREY M，KONCINA E，et al.NLRP3 inflammasome is expressed and functional in mouse microglia but not in astrocytes J .PloS One，2015，10(6 )：e130624DOI：10.13194/j.issn.1673-842x.2023.01.00626 辽宁中医药大学学报 25 卷Hospital of Liaoning University of Traditional Chinese Medicine，Shenyang 110032，Liaoning，China）Abstract：Objective To study the effect of traditional Chinese medicine compound on the levels of tumor necrosis factor-（TNF-）and intercellular adhesion molecule-1（ICAM-1）in serum of rats with atrial fibrillation，and to explore the possible mechanism of traditional Chinese medicine compound prescription in the prevention and treatment of atrial fibrillation.Methods 60 male SD rats were randomly divided into blank group（n=10）and modeling group（n=50）.The rat model of atrial fibrillation was established by injecting Ach（66 g/mL）-CaCl2（10 mg/mL）mixture into tail vein for 7 days.The successful rats were randomly divided into five groups：model group，high dose group，middle dose group，low dose group and verapamil group，continuous intragastric administration fo