基于“以方测证”探讨阿霉素诱导慢性心衰小鼠模型中医证候属性与鸢尾素表达特点  

Characterization of TCM Syndromes and Expression of IRISIN in Mouse Model of Doxorubicin-Induced Chronic Heart Failure Based on Syndrome Differentiation by Formulas

作　　者：李欣春 王菲 赵振宇 王朝 胡思远 胡志希 LI Xinchun;WANG Fei;ZHAO Zhenyu;WANG Chao;HU Siyuan;HU Zhixi(School of Chinese Medicine,Hunan University of Chinese Medicine,Changsha 410208;Hunan Provincial Hospital of Integrated Traditional Chinese and Western Medicine,Changsha 410006;School of Sports&Arts,Hunan University of Chinese Medicine,Changsha 410208)

机构地区：[1]湖南中医药大学中医学院,长沙410208 [2]湖南省中西医结合医院,长沙410006 [3]湖南中医药大学体育艺术学院,长沙410208

出　　处：《中药药理与临床》2024年第10期74-79,共6页Pharmacology and Clinics of Chinese Materia Medica

基　　金：国家自然科学基金面上项目(编号:82274412);湖南省教育厅优秀青年项目(编号:21B0361);湖南中医药大学研究生创新课题项目(2023CX01)。

摘　　要：目的:研究阿霉素诱导的慢性心力衰竭(Chronic Heart Failure,CHF)小鼠模型的病理特点,并从“以方测证”角度评价该模型中医证候属性及生物标志物鸢尾素(IRISIN)的表达特点。方法:小鼠腹腔注射阿霉素5 mg/kg造模,造模成功后将其按随机数字表法分为模型对照组、参附注射液9 mL/kg组、参麦注射液9 mL/kg组和丹红注射液6 mL/kg组。各组腹腔注射相应药物或生理盐水,采用多普勒心脏彩超记录小鼠LVEF、LVFS和SV;ELISA法测定小鼠血清和心肌组织NT-pro BNP、CK-MB和IRISIN含量,Western blot法检测心肌组织CK-MB、IRISIN、BAX、BCL-2和Caspase 3的蛋白表达;HE染色法观察小鼠心肌组织损伤状态,再结合宏观表征探讨该模型中医证型并分析IRISIN在该模型中的表达特点及意义。结果:中药注射液干预后,与正常对照组比较,模型对照组LVEF、LVFS、SV降低,血清NT-pro BNP及CK-MB含量升高,IRISIN含量降低,心肌组织CK-MB、BAX和Caspase3蛋白表达上调,IRISIN、BCL-2蛋白表达下调(P<0.05或P<0.01);与模型对照组比较,参附注射液9 mL/kg组小鼠LVEF、LVFS和SV升高,血清NT-pro BNP、CK-MB含量降低,IRISIN含量显著升高,心肌组织IRISIN蛋白表达上调,CK-MB和NT-pro BNP蛋白表达下调(P<0.05或P<0.01);参麦注射液9 mL/kg组LVEF、LVFS降低,血清IRISIN含量升高,心肌组织NT-pro BNP表达下调,IRISIN表达上调(P<0.05或P<0.01);丹红注射液6 mL/kg组LVEF、LVFS降低,心肌组织NT-pro BNP和IRISIN含量升高(P<0.01)。心肌组织HE染色结果表明,正常对照组和参附注射液9 mL/kg组心肌组织基本处于正常状态,心肌细胞形态规则、排列整齐;与参附注射液9 mL/kg组比较,模型对照组、参麦注射液9 mL/kg组和丹红注射液6 mL/kg组处于轻度或中度心肌损伤状态,心肌呈波浪状,细胞水肿,轻度空泡变性并伴有不同程度的炎症细胞浸润和间质水肿。结论:参附注射液是治疗阿霉素诱导CHF动物模型的有效中药制�Objective:To study the pathological characteristics of the mouse model of chronic heart failure(CHF)induced by doxorubicin(DOX)and evaluate the traditional Chinese medicine(TCM)syndromes and the expression characteristics of IRISIN based on syndrome differentiation by formulas.Methods:The mouse model was established by intraperitoneal injection of DOX at 5 mg/kg.The successfully modeled mice were assigned with the random number table method into model,Shenfu(参附)injection(9 mL/kg),Shenmai(参麦)injection(9 mL/kg),and Danhong(丹红)injection(6 mL/kg)groups.During the intervention period,mice in the model group and normal group were intraperitoneally injected with normal saline at a dose of 9 mL/kg.After modeling and drug intervention,the left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS),and stroke volume(SV)of mice in each group were recorded by Doppler echocardiography.After drug intervention,the expression levels of N-terminal-pro brain-derived natriuretic peptide(NT-pro BNP),creatine kinase-MB(CK-MB),and IRISIN in the serum and myocardium were measured,and the expression levels of CK-MB,IRISIN,B-cell lymphoma-2(BCL-2),BCL-2-associated protein X(BAX),and Caspase 3 in the myocardium of the normal and model groups were determined.Hematoxylin-eosin(HE)staining was used to observe the injury state of myocardial tissue in mice.Macroscopic characterization was employed to explore the TCM syndromes of the model and analyze the expression characteristics and significance of IRISIN in the model.Results:After drug intervention,compared with the normal group,the model group showed decreased LVEF,LVFS,and SV,up-regulated expression of NT-pro BNP and CK-MB and down-regulated expression of IRISIN in the serum,and up-regulated expression of CK-MB,BAX,and Caspase 3 and down-regulated expression of IRISIN and BCL-2 in the myocardial tissue(P<0.01 or P<0.05).Compared with the model group,Shenfu injection(9 mL/kg)increased the LVEF,LVFS,and SV,down-regulated the expression of NT-pro BNP and

关 键 词：参附注射液 阿霉素 慢性心力衰竭 以方测证 中医证候 鸢尾素 

分 类 号：R285.5[医药卫生—中药学]