黄芪多糖下调心肌p38和核因子κB的磷酸化改善老年糖尿病鼠心脏功能  

Astragalus polysaccharide down-regulates the phosphorylation ofmyocardial p38 and nuclear factor-κB and improves heart function of elderly diabetic mice

作　　者：孙奇林 陈雯洁 赵雪兰 王浩[2] 陈蔚 Sun Qilin;Chen Wenjie;Zhao Xuelan;Wang Hao;Chen Wei(Department of Geriatrics,Huashan Hospital,Fudan University,Shanghai,200040;BasicMedical Experimental Teaching Center,Fudan University,Shanghai,200032,P.R.China)

机构地区：[1]复旦大学附属华山医院老年科,上海200040 [2]复旦大学基础医学实验教学中心,上海200032

出　　处：《老年医学与保健》2021年第2期399-404,共6页Geriatrics & Health Care

基　　金：国家自然科学基金面上项目(82074199);上海市科委自然科学基金(20ZR1409200)。

摘　　要：目的探讨黄芪多糖(APS)对老年糖尿病(DM)鼠心肌纤维化的影响。方法 18月龄的C57BL/6J小鼠30只随机分为对照(NS)组、老年DM组和老年APS组,每组10只。老年DM组和老年APS组采用链脲佐菌素腹腔注射法制作DM动物模型。老年APS组予APS 2 g/kg/d灌胃,NS组和老年DM组予等体积生理盐水灌胃。干预16周后,观察小鼠的血糖和心肌酶谱;测定心脏功能及血流动力学指标;评估心肌胶原纤维化程度;检测金属蛋白酶1(MMP1)、MMP3、MMP9、白细胞介素-1α (IL-1α)、IL-6、转化生长因子-β(TGF-β)、胞外信号调节激酶(ERK) 1/2、Jun激酶(JNK)、p38丝裂原激活蛋白激酶(MAPK)及核因子κB (NF-κB)/p65的蛋白表达。结果与NS组相比,老年DM组空腹血糖、糖化血清蛋白、心肌酶谱和左心室舒张末期压(LVEDP)升高(均P<0.01);左心室短轴缩短率、左心室收缩压、左室内压最大上升速率(+dP/dtmax)及左室内压最大下降速率降低(均P<0.01);Ⅰ型胶原纤维含量和Ⅰ/Ⅲ型胶原纤维比值升高(均P<0.01),心肌病理结构严重损伤;MMP1、MMP3、MMP9、IL-1α、IL-6和TGF-β蛋白表达升高(均P<0.01);ERK1/2、JNK、p38 MAPK及NF-κB/p65的蛋白磷酸化水平升高(均P<0.01)。与老年DM组相比,老年APS组p38 MAPK及NF-κB/p65蛋白磷酸化水平降低(均P<0.01)。而NS组与老年APS组的LVEDP、+dP/dtmax、胶原纤维含量、MMP1、MMP9、NF-κB/p65蛋白磷酸化水平差异均无统计学意义。结论 APS可以改善老年DM鼠的心肌纤维化,可能与其下调心肌p38 MAPK和NF-κB/p65的磷酸化水平相关。Objective To investigate the effect of astragalus polysaccharide(APS) on myocardial fibrosis in elderly diabetic mice.Methods Thirty 18-month-old C57 BL/6 J mice were randomly divided into the control(NS) group,elderly DM group and elderly APS group,with 10 mice in each group.DM model was established by intraperitoneal injection of streptozotocin in DM group and APS group.The elderly APS group was given APS 2 g/kg/d by gavage for 16 weeks,and the NS group and the elderly DM group were given an equal volume of normal saline.After 16 weeks of intervention,the levels of blood glucose,myocardial enzymes,metalloproteinase-1(MMP1),MMP3,MMP9,interleukin-1α(IL-1α),IL-6,transforming growth factor-β(TGF-β) and the protein expression levels of extracellular signal regulated kinase(ERK) 1/2,Jun kinase(JNK),p38 mitogen activated protein kinase(MAPK) and nuclear factor kappa B(NF-κB)/p65 were detected,the cardiac function and hemodynamics of mice were measured,and the degree of myocardial collagen fibrosis was evaluated.Results Compared with the NS group,the fasting blood glucose,glycosylated serum protein,myocardial enzyme spectrum and left ventricular end diastolic pressure(LVEDP) in the elderly DM group increased(allP<0.01),the left ventricular short axis shortening rate,left ventricular systolic pressure,the maximum increase rate of left ventricular pressure(+dP/dtmax) and the maximum decrease rate of left ventricular pressure decreased(both P<0.01),the content of type Ⅰ collagen fibers and the ratio of type Ⅰ/Ⅲ collagen fibers increased(both P<0.01),the pathological structure of myocardium was more seriously damaged,protein expression of MMP1,MMP3,MMP9,IL-1α,IL-6 and TGF-β increased(all P<0.01),protein phosphorylation level of ERKⅠ/2,JNK,p38 MAPK and NF-κB/p65 increased(all P<0.01).Compared with the elderly DM group,the phosphorylation levels of p38 MAPK and NF-κB/p65 protein in the elderly APS group were lower(all P<0.01).But there were no statistically significant differences in LVEDP,+dP/dtmax,collagen

关 键 词：老年 糖尿病 黄芪多糖 心肌纤维化 P38丝裂原激活蛋白激酶 核因子κB/p65 

分 类 号：R285.5[医药卫生—中药学]