桑白皮多糖介导Nrf2/ARE通路减轻慢性低氧环境大鼠心肌损伤的作用  

Effect of cortex mori polysaccharide mediating Nrf2/ARE pathway on alleviating myocardial injury in rats under chronic hypoxic environment

作　　者：王晓磊 黄辉 陈昕芳 李红[1] WANG Xiao-Lei;HUANG Hui;CHEN Xin-Fang(Deaprtment of Lung Diseases,Kunshan Hospital of Traditional Chinese Medicine,Kunshan 215300,Jiangsu,China)

机构地区：[1]昆山市中医医院肺病科,江苏昆山215300

出　　处：《中国老年学杂志》2024年第7期1632-1637,共6页Chinese Journal of Gerontology

基　　金：国家自然科学基金资助项目(82004271);江苏省基础研究计划(自然科学基金)(BK20200260)。

摘　　要：目的 探讨桑白皮多糖对慢性低氧环境所致的大鼠心肌损伤的影响,并观察其介导转录因子NF-E2相关因子(Nrf)2/抗氧化反应元件(ARE)通路的机制。方法 60只7~9周龄SD大鼠采用随机数字表分为对照组、模型组、阿托伐他汀组、桑白皮多糖低、中、高剂量组。除对照组外,其余各组均置于常压低氧舱内构建心肌损伤大鼠模型,对照组呼吸室内空气。自低氧第1天起,阿托伐他汀组给予20 mg/kg阿托伐他汀腹腔注射给药,桑白皮多糖低、中、高剂量组分别给予0.1、0.2、0.4μg/ml桑白皮多糖腹腔注射给药;对照组和模型组仅腹腔注射生理盐水。给药后24 h,苏木素-伊红(HE)染色观察各组心肌组织病变情况;原位末端标记法(TUNEL)检测各组心肌细胞凋亡率;酶联免疫吸附试验(ELISA)检测各组血清血浆肌酸激酶(CK)、乳酸脱氢酶(LDH)、心肌组织超氧化物歧化酶(SOD)活性和丙二醛(MDA)水平;检测心肌组织Nrf2、血红素加氧酶(HO)-1、B细胞淋巴瘤(Bcl)-2、Bcl-2相关X蛋白(Bax)mRNA及蛋白、p-Nrf2表达。结果 模型组心肌严重损伤,阿托伐他汀组和桑白皮多糖各剂量组均减轻;与对照组比较,模型组细胞凋亡率、CK、LDH活性和MDA水平、Bax mRNA和蛋白表达和p-Nrf2均明显上升,SOD活性、Nrf2、HO-1、Bcl-2 mRNA和蛋白表达明显下降(P<0.05);与模型组比较,阿托伐他汀组和桑白皮多糖各剂量组细胞凋亡率、CK、LDH活性和MDA水平、Bax mRNA和蛋白表达明显下降,SOD活性、Nrf2、HO-1、Bcl-2 mRNA和蛋白、p-Nrf2表达明显升高(P<0.05);桑白皮多糖对上述指标的作用与剂量有关。结论 桑白皮多糖可减轻慢性低氧环境大鼠心肌损伤,可能与激活Nrf2/ARE通路相关。Objective To investigate the effect of cortex mori polysaccharide on myocardial injury in rats under chronic hypoxic environment,and to observe its effect on mediating transcription factor NF-E2-related factor(Nrf)2/antioxidant response element(ARE)pathway.Methods Sixty SD rats aged 7~9 weeks were divided into control,model,atorvastatin groups,and low,medium,high-dose groups of cortex mori polysaccharide using a random number table.Except for the control group,all other groups were placed in a atmospheric low oxygen chamber to construct a rat model of myocardial injury,while the control group breathed indoor air.Starting from the first day of hypoxia,the atorvastatin group was given 20 mg/kg of atorvastatin by intraperitoneal injection,and the low,medium,high dose groups of cortex mori polysaccharide were given 01,0.2,0.4μg/ml cortex mori polysaccharide administered by intraperitoneal injection,while the control group and model group were only given intraperitoneal injection of physiological saline.After 24 h of administration,hematoxylin eosin(HE)staining was used to observe the pathological changes of myocardial tissues in each group.TdT-mediated dUTP nick end labeling(TUNEL)was used to detect the apoptosis rates of myocardial cells in each group.Enzyme linked immunosorbent assay(ELISA)was used to detect the levels of serum creatine kinase(CK),lactate dehydrogenase(LDH),myocardial tissue superoxide dismutase(SOD)activities,and malondialdehyde(MDA)in each group.The expressions of myocardial tissue Nrf2,heme oxygenase(HO)-1,B-cell lymphoma(Bcl)-2,Bcl-2 related X protein(Bax)mRNA,protein,and p-Nrf2 were detected.Results The model group suffered from severe myocardial injury,the atorvastatin group and the cortex mori polysaccharide groups at different doses all showed relief.Compared with the control group,cell apoptosis rate,CK,LDH activity,MDA levels,Bax mRNA and protein expressions,p-Nrf2 were significantly increased,while SOD activity,Nrf2,HO-1,Bcl-2 mRNA and protein expressions were significantly decreased in

关 键 词：桑白皮多糖 慢性低氧环境心肌损伤 转录因子NF-E2相关因子2 抗氧化反应元件 心肌细胞凋亡 氧化应激 

分 类 号：R285.5[医药卫生—中药学]