D-β-羟基丁酸通过激活Notch1/Hes1通路和抑制内质网应激改善大鼠急性心肌梗死  

D-β-hydroxybutyrate improves acute myocardial infarction in rats by activating Notch1/Hes1 pathway and inhibiting endoplasmic reticulum stress

作　　者：刘婷婷[1] 董红艳 马艳兰 王婷婷[4] 王学武[5] LIU Tingting;DONG Hongyan;MA Yanlan;WANG Tingting;WANG Xuewu(Department of Cadre Health Care,The People's Hospital of Xinjiang Uygur Autonomous Region,Urumqi 830000,China;Department of Acupuncture and Moxibustion,Changji Hospital of Traditional Chinese Medicine,Changji 831100,Xinjiang,China;Department of Child Rehabilitation,Yili Maternal and Child Health Hospital,Yining 835000,Xinjiang,China;Department of Pharmacy,The People's Hospital of Xinjiang Uygur Autonomous Region,Xinjiang 830000,China;Department of Traditional Chinese Medicine,The People's Hospital of Xinjiang Uygur Autonomous Region,Urumqi 830000,China)

机构地区：[1]新疆维吾尔自治区人民医院干部保健科,新疆乌鲁木齐830000 [2]新疆昌吉州中医医院针灸科,新疆昌吉831100 [3]新疆伊犁州妇幼保健院儿童康复科,新疆伊宁835000 [4]新疆维吾尔自治区人民医院药学部,新疆乌鲁木齐830000 [5]新疆维吾尔自治区人民医院中医科,新疆乌鲁木齐830000

出　　处：《西部医学》2022年第12期1736-1742,共7页Medical Journal of West China

基　　金：新疆维吾尔自治区自然科学基金项目(2019D01C219)。

摘　　要：目的探究D-β-羟基丁酸(DβHB)对大鼠急性心肌梗死(AMI)的作用及其可能的作用机制。方法40只SPF级SD大鼠随机分为对照组、心梗组、DβHB组和阳性对照组,每组10只。除对照组外,其余组通过结扎冠状动脉左前降支近端建立AMI大鼠模型。DβHB组大鼠腹腔注射DβHB 100 mg·kg^(-1)·d^(-1),阳性对照组大鼠腹腔注射倍他乐克12 mg·kg^(-1)·d^(-1),对照组和心梗组大鼠注射等量生理盐水,持续给药3周。超声心动图检测心功能;HE染色检测心脏病理学变化;TTC染色检测心肌梗死面积;ELISA试剂盒检测LDH和CK-MB活性;TUNEL染色检测心肌细胞凋亡;Western blot检测凋亡、Notch1/Hes1通路和内质网应激相关蛋白水平。结果与对照组相比,心梗组大鼠心肌结构紊乱,存在明显炎性细胞浸润和间质水肿,心功能明显降低,心肌梗死面积、LDH活性、CK-MB活性、心肌细胞凋亡率、Bax、p-PERK/PERK、p-eIF2α/eIF2α、ATF4和CHOP蛋白表达明显升高(均P<0.05),Bcl-2蛋白水平明显降低(P<0.05),Notch1、NICD和Hes1蛋白水平差异无统计学意义(P>0.05);与心梗组相比,DβHB组和阳性对照组大鼠心肌病理学变化有明显改善,心功能明显提升,心肌梗死面积、LDH活性、CK-MB活性、心肌细胞凋亡率、Bax、p-PERK/PERK、p-eIF2α/eIF2α、ATF4和CHOP蛋白水平明显降低(P<0.05),Bcl-2、Notch1、NICD和Hes1蛋白水平明显升高(P<0.05)。结论DβHB可能通过激活Notch1/Hes1通路和抑制内质网应激改善大鼠急性心肌梗死。Objective To explore the effect of D-β-hydroxybutyrate(DβHB)on acute myocardial infarction(AMI)in rats and its possible mechanism.Methods Forty SD rats were randomly divided into control group,myocardial infarction group,DβHB group and positive control group,with 10 rats in each group.Except for the control group,the remaining groups established AMI rat models by ligating the proximal end of the left anterior descending coronary artery.Rats in the DβHB groups were intraperitoneally injected with DβHB 100 mg/kg/d,rats in the positive control group were intraperitoneally injected with Betaloc 12 mg/kg/d,and rats in the control and myocardial infarction groups were injected with the same amount of normal saline for 3 weeks.Echocardiography was used to detect cardiac function;HE staining was used to detect cardiology changes;TTC staining was used to detect myocardial infarction area.ELISA kit was used to detect LDH and CK-MB activity.TUNEL staining was used to detect myocardial cell apoptosis.Western blot was used to detect apoptosis,Notch1/Hes1 pathway and endoplasmic reticulum stress-related protein expression.Results Compared with the control group,the myocardial infarction group had disordered myocardial structure,obvious inflammatory cell infiltration and interstitial edema,cardiac function was significantly reduced,myocardial infarction area,LDH activity,CK-MB activity,myocardial cell apoptosis rate,Bax,p-PERK/PERK,p-eIF2α/eIF2α,ATF4 and CHOP protein expression were significantly increased(P<0.05),Bcl-2 protein expression was significantly decreased(P<0.05).The differences of Notch1,NICD and Hes1 protein expression were not statistical significance(P>0.05).Compared with the myocardial infarction group,the myocardial pathology changes in the DβHB group and positive control group were significantly improved,the cardiac function was significantly improved,myocardial infarction area,LDH activity,CK-MB activity,myocardial cells Apoptosis rate,Bax,p-PERK/PERK,p-eIF2α/eIF2α,ATF4 and CHOP protein expression w

关 键 词：D-β-羟基丁酸 急性心肌梗死 Notch1/Hes1通路 内质网应激 

分 类 号：R329.25[医药卫生—人体解剖和组织胚胎学]