白芨多糖对心肌梗死大鼠PI3K/AKT/GRP78信号通路及心肌细胞内质网应激凋亡的影响  

Effects of Bletilla striata polysaccharide on PI3K/AKT/GRP78 signaling pathway and endoplasmic reticulum stress apoptosis in myocardial infarction rats

作　　者：王建营[1] 李晶 于飞 姚光[1] 解立杰 张全意[1] WANG Jian-Ying;LI Jing;YU Fei(Binzhou Medical University Hospital,Binzhou 256603,Shandong,China)

机构地区：[1]滨州医学院附属医院,山东滨州256603

出　　处：《中国老年学杂志》2022年第1期108-112,共5页Chinese Journal of Gerontology

基　　金：国家自然科学基金青年科学基金资助项目(81900269)。

摘　　要：目的探究白芨多糖对心肌梗死(MI)大鼠磷脂酰肌醇-3-激酶(PI3K)/蛋白激酶B(AKT)及葡萄糖调节蛋白(GRP)78信号通路蛋白表达及对心肌细胞内质网(ERS)凋亡的影响。方法SD大鼠随机分为假手术组、模型组、白芨多糖低(100 mg/kg)、中(200 mg/kg)、高(400 mg/kg)剂量组、阳性对照组(卡托普利,2.25 mg/kg),每组10只。采用冠状动脉结扎法建立大鼠MI模型,连续给药4 w,1次/d后,取心肌组织和颈动脉血,用三苯基氯化四氮唑(TTC)染色检测MI面积;苏木素-伊红(HE)染色法检测心肌病理形态;Tunel法检测心肌细胞凋亡率;酶联免疫吸附试验(ELISA)检测血清中磷酸肌酸同工酶(CK-MB)、肌钙蛋白(cTn)I水平;Western印迹检测PI3K/AKT/GRP78通路蛋白及下游蛋白激酶R样内质网激酶(PERK)/真核细胞翻译起始因子(eIF)2α、促凋亡蛋白半胱氨酸天冬氨酸蛋白酶(caspase)-12相对表达水平。结果与假手术组相比,其余各组心肌组织纤维变性、间质水肿、炎性细胞浸润等病理损伤严重,MI面积、心肌细胞凋亡率显著升高,PI3K/AKT通路蛋白表达显著降低,其介导的内质网应激凋亡GRP78/PERK/eIF2α/caspase-12通路蛋白表达显著升高(均P<0.05)。与模型组相比,白芨多糖各剂量组及阳性对照组心肌组织病理损伤减轻,MI面积、心肌细胞凋亡率显著降低,PI3K/AKT通路蛋白表达显著升高,其介导的内质网应激凋亡GRP78/PERK/eIF2α/caspase-12通路蛋白表达显著降低(P<0.05),且白芨多糖剂量越高上述指标改善效果越明显(P<0.05)。结论白芨多糖可激活PI3K/AKT通路,抑制GRP78/PERK/eIF2α信号通路蛋白表达,降低心肌细胞ERS凋亡,改善MI大鼠心肌坏死。Objective To investigate the effects of Bletilla striata polysaccharide on the expressions of phosphatidylinositol-3-kinase(PI3K)/protein kinase B(AKT)and glucose regulated protein(GRP)78 signaling pathway protein in rats with myocardial infarction(MI)and on the apoptosis of endoplasmic reticulum of cardiomyocytes(ERS).Methods SD rats were randomly divided into sham operation group,model group,Bletilla striata polysaccharide low(100 mg/kg),medium(200 mg/kg),high(400 mg/kg)dose groups and captopril positive control group(2.25 mg/kg),with 10 rats in each group;a rat MI model was established by coronary artery ligation.After 4 weeks of continuous administration,once a day.the myocardial tissue and carotid blood were collected;and stained with 2,3,5-triphenyltetrazoliumchloride(TTC)to detect the area of myocardial infarction;Lignin-eosin staining method was used to detect the pathological morphology of the myocardial group;enzyme linked immunosorbent assay(ELISA)was used to detect the levels of CK-MB and cTnI;Western blot was used to detect PI3K/AKT/GRP78 pathway proteins,and downstream protein kinase R-like endoplasmic reticulum kinase(PERK)/eukaryotic translation and the relative expression levels of initiation factor(eIF2α)and pro-apoptotic protein caspase(caspase)-12.Results Compared with the sham operation group,the rats in the model group had severe pathological damage such as myocardial tissue fibrosis,interstitial edema,and inflammatory cell infiltration,the infarct size and the apoptosis rate of myocardial cells increased,and the expression of PI3K/AKT pathway protein decreased,the expression of GRP78/PERK/eIF2α/caspase-12 pathway protein increased in endoplasmic reticulum stress and apoptosis(P<0.05).Compared with the model group,rats in the Bletilla striata polysaccharide dose group and the positive control group had reduced myocardial tissue pathological damage,reduced infarct size and myocardial cell apoptosis,decreased PI3K/AKT pathway protein expression,and its mediated endoplasmic reticulum stress a

关 键 词：白芨多糖 心肌梗死 磷脂酰肌醇-3-激酶/蛋白激酶B 葡萄糖调节蛋白78 内质网应激 凋亡 

分 类 号：R541.4[医药卫生—心血管疾病]