维生素D介导MEK/ERK通路对妊娠糖尿病大鼠心肌损伤的影响  

Effects of vitamin D mediated MEK/ERK pathway on myocardial damage in rats with gestational diabetes mellitus

作　　者：贾二霞[1] 徐娜 李帅 舒秋芳[1] JIA Er-xia;XU Na;LI Shuai;SHU Qiu-fang(Department of Obstetrics,The Fourth People's Hospital of Jinan,Jinan 250031,Shandong Province,China)

机构地区：[1]济南市第四人民医院产科,山东济南250031

出　　处：《中国临床药理学杂志》2024年第7期1014-1018,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的研究维生素D介导丝裂原激活蛋白激酶(MEK)/细胞外信号调节激酶(ERK)通路对妊娠糖尿病大鼠心肌损伤的影响。方法将SD大鼠分为对照组、模型组和低、中、高剂量实验组。除对照组外,各组建立妊娠糖尿病大鼠模型。造模成功后,低、中、高剂量实验组分别灌胃给予0.05、0.10.0.15μg·kg^(-1)的维生素D,对照组、模型组均灌胃等量0.9%NaCl,每天1次,连续灌胃2周。检测干预前和干预后1周、2周空腹血糖浓度、胰岛素水平,以超声心动图检测心功能[左心室射血分数(LVEF)、左心室内压最大上升速度(+dp/dt_(max))和最大下降速度(-dp/dt_(max))],以酶联免疫吸附试验(ELISA)法检测大鼠血清和心肌组织中心肌酶指标[肌钙蛋白Ⅰ(cTnⅠ)、肌酸激酶同工酶(CK-MB)]、炎性因子[肿瘤坏死因子-α(TNF-α)、C反应蛋白(CRP)]水平,以蛋白质印迹法检测MEK/ERK通路蛋白的表达水平。结果对照组、模型组和低、中、高剂量实验组心肌组织cTnⅠ水平分别为(10.50±1.08)、(42.26±4.30)、(31.85±2.44)(23.31±2.15)和(14.85±1.19)ng·mL^(-1),血清cTnⅠ水平分别为(23.79±3.46)、(63.59±5.52)、(51.02±4.27)、(42.75±3.19)和(29.20±2.11)ng·mL^(-1),心肌组织CK-MB水平分别为(8.52±0.90)、(17.65±1.75)、(15.62±1.27)、(13.11±1.24)和(9.85±0.87)ng·mL^(-1),血清CK-MB水平分别为(11.32±0.98)、(21.24±1.45)、(18.75±1.32)、(15.11±1.02)和(12.27±1.11)ng·mL^(-1),磷酸化MEK蛋白相对表达水平分别为0.24±0.03、0.85±0.09、0.72±0.06、0.57±0.07和0.35±0.04,磷酸化ERK1/2蛋白相对表达水平分别为0.18±0.02、0.66±0.07、0.52±0.06、0.40±0.07和0.24±0.05。对照组的上述指标与模型组,在统计学上差异均有统计学意义(均P<0.05);模型组的上述指标与低、中、高剂量实验组比较,在统计学上差异均有统计学意义(均P<0.05)。结论维生素D可能通过抑制MEK/ERK通路激活,进而减轻妊娠糖尿病大鼠心肌损伤。Objective To investigate the effects of vitamin D mediated mitogen-activated protein kinase(MEK)/extracellular signal-regulated kinase(ERK)pathway on myocardial injury in rats with gestational diabetes mellitus.Methods Fifty SD rats were divided into control group,model group,experimental-L group,experimental-M group and experimental-H group,and the gestational diabetes rat model was established.After successful modeling,experimental-L,experimental-M,experimental-H groups were given intragastric administration of 0.05,0.10 and 0.15μg·kg^(-1) concentration of vitamin D,while control group and model group were given intragastric administration of 0.9%NaCl at the same dose once a day for 2 weeks.Fasting blood glucose concentration and insulin level were detected before intervention,1 week and 2 weeks after intervention.Echocardiography was used to detect cardiac function[left ventricular ejection fraction(LVEF),maximum rate of rise(+dp/dt_(max))and maximum rate of decline(-dp/dt_(max))of left ventricular pressure].Myocardial enzyme indexes[troponin I(cTn I)kit,creatine kinase isoenzyme(CK-MB)]and inflammatory factors[tumor necrosis factor-α(TNF-α),C-reactive protein(CRP)]in serum and myocardial tissue of rats were detected by enzyme-linked immunosorbent assay(ELISA),and MEK/ERK pathway protein expression was detected by western blot.Results The levels of cTn I in cardiac tissue of control group,model group,experimental-L group,experimental-M group,experimental-H group were(10.50±1.08),(42.26±4.30),(31.85±2.44),(23.31±2.15)and(14.85±1.19)ng·mL^(-1);serum cTn I levels were(23.79±3.46),(63.59±5.52),(51.02±4.27),(42.75±3.19)and(29.20±2.11)ng·mL^(-1);myocardial tissue levels of CK-MBwere(8.52±0.90),(17.65±1.75),(15.62±1.27),(13.11±1.24)and(9.85±0.87)ng·mL^(-1);serum levels of CK-MB were(11.32±0.98),(21.24±1.45),(18.75±1.32),(15.11±1.02)and(12.27±1.11)ng mL^(-1);phosphorylated-MEK protein expression were 0.24±0.03,0.85±0.09,0.72±0.06,0.57±0.07 and 0.35±0.04;phosphorylated-ERK1/2 protein exp

关 键 词：维生素D 丝裂原激活蛋白激酶/细胞外信号调节激酶通路 妊娠糖尿病 心肌组织 心肌酶 炎性反应 

分 类 号：R977.24[医药卫生—药品]