白花前胡丁素对慢性阻塞性肺疾病慢性缺氧模型大鼠心肌损伤的防护作用  

Protective Effect of Praeruptorin D on Chronic Hypoxia-Induced Myocardial Injury in Model Rats with Chronic Obstructive Pulmonary Disease

作　　者：杜佩珊 姜爱雯[2] 田艳珍 赵东坡 毛建云 宋永建 DU Peishan;JIANG Aiwen;TIAN Yanzhen;ZHAO Dongpo;MAO Jianyun;SONG Yongjian(The First Hospital of Zhangjiakou,Zhangjiakou,Hebei,China 075000;The First Affiliated Hospital of Hebei North University,Zhangjiakou,Hebei,China 075000)

机构地区：[1]河北省张家口市第一医院,河北张家口075000 [2]河北北方学院附属第一医院,河北张家口075000

出　　处：《中国药业》2024年第22期59-64,共6页China Pharmaceuticals

基　　金：河北省中医药管理局科研课题计划项目[2025053];河北省张家口市科技计划自筹经费项目[2221152D]。

摘　　要：目的探讨白花前胡丁素(PD)对慢性阻塞性肺疾病(COPD)慢性缺氧(CH)模型大鼠心肌损伤的防护作用。方法采用烟熏联合鼻饲脂多糖复制COPD大鼠模型,正常气压下持续缺氧(氧浓度9.5%~10.5%)处理COPD模型大鼠4周,以复制COPD+CH大鼠模型。实验分为COPD组(等体积生理盐水),COPD+CH组(等体积生理盐水),PD低、高剂量组(0.1、0.5 mg/mL),核因子E2相关因子2(Nrf2)/血红素加氧酶-1(HO-1)信号通路抑制剂全反式维甲酸(ATRA)组(0.5 mg/kg),PD高剂量+ATRA组(PD 0.5 mg/mL+ATRA 0.5 mg/kg),腹腔注射药物或生理盐水,PD及生理盐水给予频率为每日1次、连续4周,ATRA为每日1次、连续2周(建模第15天起给药)。采用苏木素-伊红(HE)染色、TUNEL法分析心肌组织损伤程度及细胞凋亡情况并计算凋亡率,酶联免疫吸附法测定肌酸激酶同工酶MB(CK-MB)、乳酸脱氢酶(LDH)、心肌肌钙蛋白I(cTnI)、丙二醛(MDA)、白细胞介素6(IL-6)、白细胞介素1β(IL-1β)水平,流式细胞仪测定活性氧(ROS)水平,Western blot法测定Nrf2、HO-1蛋白表达水平。结果与COPD组比较,COPD+CH组大鼠心肌组织病理损伤及炎性反应加重,细胞凋亡率显著升高;大鼠血清CK-MB、LDH、cTnI、ROS、IL-6、IL-1β、MDA水平显著升高;Nrf2蛋白表达水平显著降低,HO-1蛋白表达水平显著升高(P<0.05)。与COPD+CH组比较,PD低、高剂量组大鼠心肌组织病理损伤及炎性反应减轻,细胞凋亡率显著降低,大鼠血清CK-MB、LDH、cTnI、ROS、IL-6、IL-1β、MDA水平显著降低,大鼠心肌组织Nrf2和HO-1蛋白表达水平显著升高;ATRA组大鼠心肌组织Nrf2和HO-1蛋白表达水平显著降低(P<0.05)。与ATRA组比较,PD高剂量+ATRA组大鼠心肌组织Nrf2和HO-1蛋白表达水平显著升高(P<0.05)。结论PD可保护COPD+CH模型大鼠心肌,其机制可能与提升Nrf2/HO-1信号通路活性有关。Objective To investigate the protective effect of praeruptorin D(PD)on the chronic hypoxia(CH)-induced myocardial injury in model rats with chronic obstructive pulmonary disease(COPD).Methods The COPD rat models were constructed by the smoke combined with nasal feeding of lipopolysaccharide,then they were subjected to persistent hypoxia under normal atmospheric pressure(9.5%-10.5%of oxygen concentration)for four weeks to construct the COPD+CH rat models.The rats were divided into the COPD group(equal volume of physiological saline),the COPD+CH group(equal volume of physiological saline),the low-and high-dose PD groups(0.1,0.5 mg/mL),the nuclear factor-erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling pathway inhibitor all-trans-retinoic acid(ATRA)group(0.5 mg/kg),the high-dose PD+ATRA group(0.5 mg/mL of PD+0.5 mg/kg of ATRA).Each group received intraperitoneal injection of drugs or physiological saline;PD and physiological saline were given once daily for four weeks,while ATRA was given once daily for two weeks,starting from the 15th day of modeling.The degree of myocardial tissue damage and cell apoptosis were analyzed by the hematoxylin eosin(HE)staining and TUNEL method,and the apoptosis rate was calculated.The levels of creatine kinase MB(CK-MB),lactate dehydrogenase(LDH),cardiac troponin I(cTnI),malondialdehyde(MDA),interleukin-6(IL-6),and interleukin-1β(IL-1β)were measured by the enzyme-linked immunosorbent assay.The reactive oxygen species(ROS)level was measured by the flow cytometry,and the expression levels of Nrf2 and HO-1 proteins were measured by the Western blot.Results Compared with those in the COPD group,the pathological damage and inflammatory response of myocardial tissue in the COPD+CH group were more serious,the apoptosis rate significantly increased;the CK-MB,LDH,cTnI,ROS,IL-6,IL-1βand MDA levels in rat serum significantly increased;the expression level of Nrf2 protein significantly decreased,and the expression level of HO-1 protein significantly increased(P<0.05).Compared

关 键 词：慢性阻塞性肺疾病 慢性缺氧 白花前胡丁素 心肌损伤 Nrf2/HO-1信号通路 

分 类 号：R965[医药卫生—药理学] R285[医药卫生—药学]