圣草次苷对大鼠缺血再灌注心肌损伤的保护作用  

Protective effect of eriocitrin from myocardial ischemia-reperfusion injury in rats

作　　者：李丽丽[1] 杨桂枝[1] 田志斌[2] 赵旭[3] 孙九艳 LI Li-li;YANG Gui-zhi;TIAN Zhi-bin;ZHAO Xu;SUN Jiu-yan(Department of Internal Medicine,Department of Clinical Medicine,Henan Nursing Vocational College,Anyang 455000,China;Department of Cardiology,Anyang District Hospital,Auyang 455000,China;Department of Surgery,Department of Clinical Medicine,Henan Vocational College of Nursing,Anyang 455000,China;Department of Neurology,Anyang People’s Hospital,Anyang 455000,China)

机构地区：[1]河南护理职业学院临床医学系内科教研室,安阳455000 [2]濮阳市安阳地区医院心内科,安阳455000 [3]河南护理职业学院临床医学系外科教研室,安阳455000 [4]河南省安阳市人民医院神经内科,安阳455000

出　　处：《药物分析杂志》2021年第9期1505-1512,共8页Chinese Journal of Pharmaceutical Analysis

基　　金：2020河南省医学教育研究项目(wjlx2020476)。

摘　　要：目的:观察圣草次苷对大鼠心肌缺血再灌注损伤(myocardial ischemia-reperfusion injury,MIRI)的保护作用,并探讨其作用机制。方法:取60只健康SD大鼠,随机分为假手术组、模型组以及圣草次苷低、中、高剂量组(8、16、32 mg·kg^(-1))、和地尔硫组,每组10只,采用手术结扎法构建心肌缺血再灌注损伤模型;圣草次苷低、中、高剂量组以及地尔硫组于造模前1周开始灌喂给药,模型组和假手术组给予等量生理盐水灌喂。再灌注结束后,通过苏木精-伊红(hematoxylin-eosin,HE)染色观察大鼠心肌组织病理改变;脱氧核糖核苷酸末端转移酶介导的脱氧三磷酸尿苷缺口末端标记法(terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling,TUNEL)染色检测心肌细胞凋亡情况;采用酶联免疫吸附法检测血清肿瘤坏死因子α(tumor necrosis factorα,TNF-α)、白介素6(interleukin 6,IL-6)、白介素1β(interleukin 1β,IL-1β)、肌钙蛋白(cardiac troponin,cTnI)、肌红蛋白(myohemoglobin,Mb)、肌酸激酶同工酶(creatine kinase MB,CK-MB)含量水平;Western blot检测心肌组织c-Myc、Bcl-2相关X蛋白(Bcl-2 associated X protein,Bax)、B淋巴细胞瘤-2(B-cell lymphoma-2,Bcl-2)、半胱氨酸天冬氨酸蛋白酶3(caspase-3)、半胱氨酸天冬氨酸蛋白酶3剪切体(Cleaved caspase-3)、JAK激酶2(Janus kinase 2,JAK2)、磷酸化JAK2(phosphorylated JAK2,p-JAK2)、信号转导与转录激活因子3(signal transducer and activator oftranscription 3,STAT3)、磷酸化STAT3(phosphorylated STAT3,p-STAT3)蛋白表达。结果:与假手术组比较,模型组HR、LVEF、FS、LVSP、LVWT、c-Myc水平显著降低(P<0.05),cTnI、Mb、CK-MB、TNF-α、IL-6、IL-1β、Bax/Bcl-2、Cleaved caspase-3/caspase-3、p-JAK2/JAK2、p-STAT3/STAT3水平显著升高(P<0.05)。与模型组比较,圣草次苷16、32 mg·kg^(-1)组及地尔硫卓组HR、LVEF、FS、LVSP、LVWT、c-Myc水平显著升高(P<0.05),cTnI、Mb、CK-MB、TNF-α、IL-6、IL-1β、Bax/Bcl-2、CObjective:To investigate the protective effect of eriocitrin from myocardial ischemia-reperfusion injury(MIRI) in rats,and explore its action mechanism. Methods:Sixty healthy SD rats were collected and randomly divided into sham operation group,model group,low-dose,medium-dose,high-dose eriocitrin groups(erioctrin 8,16,32 mg·kg^(-1)) and diltiazem group,with 10 rats per group. MIRI model was constructed by surgical ligation method. The low-dose,medium-dose,high-dose eriocitrin groups and diltiazem group were given administration at 1 week before modeling,while model group and sham group were given the same volume of normal saline. After reperfusion,pathological changes of myocardial tissues were observed by hematoxylin-eosin(HE) staining. The apoptosis of cardiomyocytes was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling(TUNEL) staining. The levels of serum tumor necrosis factor α (TNF-α),interleukin 6(IL-6),interleukin 1β (IL-1β),cardiac troponin I(cTnI),myoglobin(Mb) and creatine kinase MB(CK-MB) were detected by enzyme-linked immunosorbent assay(ELISA). The expressions of c-Myc,Bcl-2 associated X protein(Bax),B-cell lymphoma-2(Bcl-2),cysteinyl aspartate specific protease-3(caspase-3),cleaved caspase-3,Janus kinase 2(JAK2),phosphorylated JAK2(p-JAK2),signal transducer and activator of transcription 3(STAT3) and phosphorylated STAT3(p-STAT3) proteins in myocardial tissues were detected by Western blot. Results:compared with sham group,levels of HR,LVEF,FS,LVSP,LVWT and c-Myc were significantly decreased(P<0.05),while cTnI,Mb,CK-MB,TNF-α,IL-6,IL-1β,Bax/Bcl-2,cleaved caspase-3/caspase-3,p-JAK2/JAK2 and p-STAT3/STAT3 levels were significantly increased in model group(P<0.05). Compared with model group,levels of HR,LVEF,FS,LVSP,LVWT and c-Myc were significantly increased(P<0.05),while cTnI,Mb,CK-MB,TNF-α,IL-6,IL-1β,Bax/Bcl-2,cleaved caspase-3/caspase-3,p-JAK2/JAK2 and p-STAT3/STAT3 levels were significantly decreased in 16 mg·kg^(-1) and 32 mg·kg^(-1) eriocitrin gr

关 键 词：缺血再灌注 心肌损伤 大鼠 圣草次苷 炎症细胞因子 JAK2/STAT3信号通路 

分 类 号：R917[医药卫生—药物分析学]