摘要
目的探讨血根碱调节高迁移率族蛋白B1(HMGB1)/晚期糖基化终末产物受体(RAGE)信号通路对慢性心力衰竭(CHF)大鼠心肌炎症及细胞凋亡的影响。方法通过结扎冠状动脉的左前降支建立CHF大鼠模型,随机分为CHF组、血根碱低剂量组(血根碱-L组,1.00 mg/kg血根碱)、血根碱中剂量组(血根碱-M组,2.50 mg/kg血根碱)、血根碱高剂量组(血根碱-H组,6.25 mg/kg血根碱)以及血根碱-H+rHMGB1组(6.25 mg/kg血根碱+8μg/kg rHMGB1),并以仅开胸的正常大鼠作为假手术组,每组10只大鼠。干预结束后,进行超声心动图指标[缩短分数(FS)、左室射血分数(LVEF)、室间隔厚度(IVS)以及舒张末期左心室内径(LVIDD)]检测;称取心脏质量,计算心脏指数;采用酶联免疫吸附试验(ELISA)检测各组血清中白细胞介素(IL)-1β、IL-10、肿瘤坏死因子-α(TNF-α)水平;分别采用苏木精-伊红(HE)染色、缺口末端标记(TUNEL)染色观察心脏组织病理学变化及细胞凋亡变化;采用蛋白质免疫印迹技术检测心脏组织中HMGB1、RAGE蛋白表达。结果与假手术组相比,CHF组LVIDD、心脏指数、细胞凋亡率及IL-1β、TNF-α、HMGB1蛋白、RAGE蛋白水平明显增加(P<0.05),FS、IVS、LVEF及IL-10水平明显降低(P<0.05);与CHF组相比,血根碱不同剂量组LVIDD、心脏指数、细胞凋亡率及IL-1β、TNF-α、HMGB1蛋白、RAGE蛋白水平明显降低(P<0.05),FS、IVS、LVEF及IL-10水平明显增加(P<0.05);在血根碱不同剂量组中,LVIDD、心脏指数、细胞凋亡率及IL-1β、TNF-α、HMGB1蛋白、RAGE蛋白水平均为血根碱-L组>血根碱-M组>血根碱-H组,FS、IVS、LVEF及IL-10水平均为血根碱-L组<血根碱-M组<血根碱-H组,任意两组间比较,差异均有统计学意义(P<0.05);与血根碱-H组相比,血根碱-H+rHMGB1组LVIDD、心脏指数、细胞凋亡率及IL-1β、TNF-α、HMGB1蛋白、RAGE蛋白水平均明显增加(P<0.05),FS、IVS、LVEF及IL-10水平均明显降低(P<0.05)。结论血根碱可改�
Objective To explore the effect of sanguinarine regulating the high mobility group protein B1(HMGB1)/late glycation end product receptor(RAGE)signaling pathway on myocarditis and cellular apoptosis in rats with chronic heart failure(CHF).Methods The CHF rat model was established by ligating the left anterior descending branch of the coronary artery.The rats were randomly divided into the CHF group,sanguinarine low dose group(sanguinarine-L group,1.00 mg/kg sanguinarine),sanguinarine medium dose group(sanguinarine-M group,2.50 mg/kg sanguinarine),sanguinarine high dose group(sanguinarine-H group,6.25 mg/kg sanguinarine)and sanguinarine-H+rHMGB1 group(6.25 mg/kg sanguinarine+8μg/kg rHMGB1).The normal rats with only thoracotomy were used as the sham surgery group,10 rats in each group.After the intervention,the echocardiographic indicators such as fractional shortening(FS),left ventricular ejection fraction(LVEF),interventricular septal thickness(IVS)and end diastolic left ventricular diameter(LVIDD)were measured;the heart was weighed and the heart index was calculated;the enzyme linked immunosorbent assay was used to detect the levels of serum interleukin(IL)-1β,IL-10 and tumor necrosis factor-α(TNF-α)in each group;the hematoxylin eosin(HE)staining was used and the notch end labeling(TUNEL)staining was adopted to observe the histopathological changes and cellular apoptosis in cardiac tissues;the protein immunoblotting technology was adopted to detect the expression of HMGB1 and RAGE proteins in cardiac tissue.Results Compared with the sham surgery group,the levels of LVIDD,cardiac index,cellular apoptosis rate,IL-1β,TNF-α,HMGB1 protein and RAGE protein in the CHF group were significantly increased(P<0.05),while the FS,IVS,LVEF and IL-10 levels were significantly decreased(P<0.05);compared with the CHF group,the LVIDD,cardiac index,cellular apoptosis rate and the expression levels of IL-1β,TNF-α,HMGB1 protein and RAGE protein in the different sanguinarine doses groups were significantly reduced(P<0.05),while
作者
张鹏
林桂雄
卓裕丰
程宏基
陈钦修
谢文杰
冯燕玲
ZHANG Peng;LIN Guixiong;ZHUO Yufeng;CHENG Hongji;CHEN Qinxiu;XIE Wenjie;FENG Yanling(Department of Cardiovascular Internal Medicine,Panyu District Hexian Memorial Hospital,Guangzhou,Guangdong 511400,China)
出处
《检验医学与临床》
CAS
2024年第19期2790-2796,共7页
Laboratory Medicine and Clinic
基金
广东省广州市科技计划项目(202102080548)
广东省基础与应用基础研究基金项目(2021B1551140064)。
关键词
血根碱
慢性心力衰竭
心肌炎症
细胞凋亡
高迁移率族蛋白B1
晚期糖基化终末产物受体
信号通路
sanguinarine
chronic heart failure
myocardial inflammation
cellular apoptosis
high mobility group protein B1
late glycation end product receptor
signaling pathway
