加味涤痰汤对慢性间歇低氧模型大鼠心肌组织损伤及Keap1-Nrf2信号通路的影响  

Effects of Modified Ditan Decoction (加味涤痰汤) on Myocardial Tissue Injury and Keap1-Nrf2 Signaling Pathway in Chronic Intermittent Hypoxia Model Rats

作　　者：廖燃 陈沁 王丰[1] 刘丹[1] 李璟怡[1] 徐峰圣 王奕锦 郑海音[1] 陈丽丽 吴润华 LIAO Ran;CHEN Qin;WANG Feng;LIU Dan;LI Jingyi;XU Fengsheng;WANG Yijin;ZHENG Haiyin;CHEN Lili;WU Runhua(School of Integrated Chinese and Western Medicine,Fujian University of Traditional Chinese Medicine,Fuzhou,350122)

机构地区：[1]福建中医药大学中西医结合学院,福建福州350122

出　　处：《中医杂志》2022年第4期370-376,共7页Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金(82074192);福建省自然科学基金(2020J01716);福建中医药大学2019年校管科研课题(X2019006-重点)。

摘　　要：目的探讨加味涤痰汤对慢性间歇性低氧诱导大鼠心肌损伤的影响及可能作用机制。方法30只SD大鼠随机分为正常组、模型组、加味涤痰汤组,每组10只。模型组和加味涤痰汤组放入低氧舱内建立慢性间歇性低氧大鼠模型。加味涤痰汤组每天放进低氧舱前30 min按14.8 g/(kg·d)灌胃给药,正常组和模型组则按相同体积予生理盐水灌胃,共干预12周。检测血清心肌酶指标[包括肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)]、氧化应激指标[包括丙二醛(MDA)、谷胱甘肽(GSH)]和组织铁含量;检测心肌组织中kelch样ECH关联蛋白1(Keap1)、核红系转录因子2(Nrf2)、谷胱甘肽过氧化物酶4(Gpx4)、酰基辅酶A合成酶长链家族成员4(Acsl4)蛋白和mRNA的表达;HE染色观察心肌细胞的形态。结果与正常组比较,模型组大鼠血清CK、CK-MB、LDH、MDA上升,GSH表达和组织铁含量降低,心肌组织Keap1、Acsl4蛋白和mRNA表达增加,Nrf2、Gpx4蛋白和mRNA表达减少(P<0.05);HE染色结果显示模型组大鼠心肌组织内血管充血,淋巴细胞浸润,心肌细胞轻微水肿。与模型组比较,加味涤痰汤组大鼠血清CK、CK-MB、LDH、MDA下降,GSH表达和组织铁含量升高,心肌组织Keap1、Acsl4蛋白和mRNA表达降低,Nrf2、Gpx4蛋白和mRNA表达升高(P<0.05);HE染色显示心肌细胞病理形态有所改善。结论加味涤痰汤能有效改善慢性间歇性低氧过程中氧化应激对大鼠心脏造成的损伤,其机制可能是通过影响Keap1-Nrf2通路介导的铁死亡而发挥作用。Objective To investigate the effect of Modified Ditan Decoction(加味涤痰汤,MDD)on myocardial injury in chronic intermittent hypoxia model rats,and to explore the possible mechanism.Methods Thirty SD rats were randomly divided into normal group,model group,and MDD group,with 10 rats in each group.The rats in the model group and the MDD group were placed in a hypoxic chamber to establish a chronic intermittent hypoxia model.The rats in the MDD group was given 14.8 g/(kg·d)MDD by gavage 30 minutes before they entered the hypoxic chamer each day,while those in the normal group and the model group were given the same dose of normal saline by gavage,for 12 weeks.The serum myocardial enzyme indicators including creatine kinase(CK),CK myocardial band(CK-MB)and lactate dehydrogenase(LDH),oxidative stress indicators including malondialdehyde(MDA)and glutathione(GSH)as well as iron content in the tissue were measured.The protein and mRNA expressions of kelch-like ECH-associated protein 1(Keap1),nuclear erythroid transcription factor 2(Nrf2),glutathione peroxidase 4(Gpx4),and Acyl-CoA synthetase long-chain family member 4(Acs14)in the myocardial tissue were detected,and HE staining was used to observe the morphology of cardiomyocytes.Results Compared to those in the normal group,the serum CK,CK-MB,LDH,and MDA levels were significantly increased in the model group,and the GSH expression and iron content were significantly reduced;additionally,the protein and mRNA expressions of Keapl and Acs14 in myocardial tissue were increased,while those of Nrf2 and Gpx4 were reduced(P<0.05).HE staining showed that in the model group,there were congested blood vessels in the myocardial tissue,infiltrated lymphocytes,and slightly swollen myocardial cells.Compared to those in the model group,the serum CK,CK-MB,LDH,and MDA levels significantly decreased in the MDD group,and GSH expression and tissue iron content were significantly increased;the protein and mRNA expressions of Keapl and Acsl4 in myocardial tissue decreased,while those of

关 键 词：阻塞性睡眠呼吸暂停 慢性间歇低氧 加味涤痰汤 心肌损伤 氧化应激 铁死亡 Keap1-Nrf2通路 

分 类 号：R285.5[医药卫生—中药学]