四逆汤对阿霉素诱导的慢性心力衰竭大鼠内质网应激的影响  

Effect of Sini Decoction on Endoplasmic Reticulum Stress in Rats with Heart Failure Induced by Doxorubicin

作　　者：于游[1,2] 杜莹 南明花[2] 李佳[2] 张妤[1] 吕美君[1] 王莹[1] 吴瑾[1] 孙红[2] YU You;Du Ying;NAN Ming-Hua;LI Jia;ZHANG Yu;LUY Mei-Jun;WANG Ying;WU Jin;SUN Hong(Liaoning University of Traditional Chinese Medicine,Shenyang 110847 Liaoning,China;The Second Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110034 Liaoning,China)

机构地区：[1]辽宁中医药大学,辽宁沈阳110847 [2]辽宁中医药大学附属第二医院,辽宁沈阳110034

出　　处：《广州中医药大学学报》2021年第5期991-996,共6页Journal of Guangzhou University of Traditional Chinese Medicine

基　　金：辽宁省自然科学基金资助项目(编号:20180550109);沈阳市科技计划项目(编号:18-013-0-73)。

摘　　要：【目的】探讨四逆汤对阿霉素诱导的慢性心力衰竭(CHF)大鼠内质网应激的影响。【方法】从90只大鼠中随机选取15只作为正常组,其余大鼠腹腔注射阿霉素构建CHF模型,同时,正常组给予腹腔注射生理盐水。造模结束后,正常组大鼠全部存活,造模大鼠存活60只。再将60只CHF大鼠随机分为5组,即模型组,四逆汤低、中、高剂量组,曲美他嗪组,每组12只。四逆汤低、中、高剂量组分别给予1.4、4.2、12.6(生药)g·kg^(-1)·d^(-1)灌胃,曲美他嗪组给予曲美他嗪10 mg·kg^(-1)·d^(-1)灌胃,正常组和模型组给予相同体积的生理盐水灌胃。连续给药4周。采用小动物超声测量左心室舒张末期直径(LVEDD)、左心室射血分数(LVEF)和左心室缩短分数(LVFS)变化;采用酶联免疫吸附分析(ELISA)检测血浆脑钠肽(BNP)和血管紧张素Ⅱ(AngⅡ)水平;采用实时荧光定量聚合酶链反应(PCR)技术检测心肌组织葡萄糖调节蛋白78(GRP78)、RNA依赖的蛋白激酶样内质网激酶(PERK)和活化转录因子4(ATF4)mRNA表达。【结果】与正常组比较,模型组大鼠LVEDD显著增大,LVEF、LVFS均显著降低,血浆BNP和AngⅡ含量升高,心肌组织GRP78、PERK及ATF4 m RNA表达量升高(P <0.01);与模型组比较,四逆汤低、中、高剂量组及曲美他嗪组LVEDD降低,LVEF、LVFS均显著增加,血浆BNP和AngⅡ含量减少,心肌组织GRP78、PERK及ATF4 m RNA表达量降低,且呈剂量依赖性,其中,四逆汤高剂量组及曲美他嗪组差异均有统计学意义(P <0.05或P <0.01)。【结论】四逆汤可改善慢性心力衰竭大鼠模型心脏功能,其机制可能与抑制PERK/ATF4信号通路从而减轻内质网应激有关。Objective To explore the effect of Sini Decoction on endoplasmic reticulum stress in rats with doxorubicin-induced chronic heart failure.Methods From 90 rats,15 rats were randomly selected as normal group,the other rats were induced into chronic heart failure model by intraperitoneal injection of doxorubicin,meanwhile the normal group was given intraperitoneal injection of normal saline.After modeling,all rats survived in the normal group,and 60 rats survived in the model group.And then the 60 rats were randomly divided into model group,low-,middle-and high-dose Sini Decoction groups,trimetazidine group,12 rats in each group,the low-,middle-and high-dose Sini Decoction groups were given intragastric administration of Sini Decoction at the dosages of 1.4,4.2,12.6(crude drug)g·kg^(-1)·d^(-1),respectively,the trimetazidine group was given intragastric administration of trimetazidine at the dosage of 10 mg·kg^(-1)·d^(-1),and the normal group and model group were given intragastric administration of the same volume of normal saline.The treatment lasted 4 weeks.After medication,small animal ultrasound was used to detect the changes of left ventricular end-diastolic diameter(LVEDD),left ventricular ejection fraction(LVEF),and left ventricular fractional shortening(LVFS),enzymelinked immunosorbent assay(ELISA)was used to detect plasma levels of brain natriuretic peptide(BNP)and angiotensinⅡ(AngⅡ),real-time polymerase chain reaction(PCR)was used to detect the m RNA expression levels of glucose-regulated protein 78(GRP78),protein kinase RNA-like endoplasmic reticulum kinase(PERK)and activating transcription factor 4(ATF4) in cardiac muscle tissue.Results Compared with the normal group,LVEDD was increased,LVFS and LVEF were decreased in the model group,contents of plasma BNP and AngⅡwere increased,and the m RNA expression levels of GRP78,PERK and ATF4 were increased(P<0.01).Compared with the model group,LVEDD was decreased,LVFS and LVEF were increased in the low-,middleand high-dose Sini Decoction groups and trime

关 键 词：四逆汤 心力衰竭 内质网应激 葡萄糖调节蛋白78 RNA依赖的蛋白激酶样内质网激酶 活化转录因子4 大鼠 

分 类 号：R285.5[医药卫生—中药学]