红景天苷调节AGE-RAGE信号通路对妊娠糖尿病大鼠心肌损伤的影响  

Effects of salidroside on myocardial injury in gestational diabetes mellitus rats by regulating AGE-RAGE signaling pathway

作　　者：潘娱 宋园 PAN Yu;SONG Yuan(Department of Obstetrics,Xi’an Gaoxin Hospital,Xi’an,Shaanxi 710000,China)

机构地区：[1]西安高新医院产科,陕西西安710000

出　　处：《中国优生与遗传杂志》2024年第8期1593-1599,共7页Chinese Journal of Birth Health & Heredity

摘　　要：目的探究红景天苷(Sal)调节晚期糖基化终末产物(AGE)及其受体(RAGE)信号通路对妊娠糖尿病(GDM)大鼠心肌损伤的影响。方法随机选取10只健康孕鼠为健康组,GDM大鼠模型随机分为GDM组(灌胃生理盐水)、L-Sal组(灌胃25 mg/kg Sal)、H-Sal组(灌胃100 mg/kg Sal)、AGE组(灌胃100 mg/kg Sal+尾静脉注射10 mg/kg AGE血清蛋白)和FBS-ZMI组(灌胃100 mg/kg Sal+腹腔注射150 mg/kg FBS-ZMI),健康组灌胃生理盐水。采用超声影像分析大鼠左室射血分数(LVEF)、左室短轴缩短率(FS)、舒张末期左心室内径(LVEDD)、收缩末期左心室内径(LVESD),全自动生化分析仪检测血清心肌损伤指标肌酸激酶同工酶(CK-MB)、心肌肌钙蛋白I(cTnI)、N端脑钠肽前体(NT-proBNP)水平;计算心脏质量指数(HWI);H-E染色和Masson染色观察心肌组织形态;酶联免疫吸附法(ELISA)检测肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-6、IL-10、丙二醛(MDA)、谷胱甘肽(GSH)、超氧化物歧化酶(SOD)水平,亚铁嗪比色法分析组织总铁离子含量;免疫印迹法测定组织中AGE、RAGE、谷胱甘肽过氧化物酶4(GPX4)、酰基辅酶A合酶4(ACSL4)、Bcl2蛋白表达。结果与健康组相比,GDM组心肌组织病理变化加重,空腹血糖、LVEDD、LVESD、HWI、胶原体积分数(CVF)、CK-MB、cTnI、NT-proBNP、总铁离子含量、TNF-α、IL-6、MDA水平及AGE、RAGE、ACSL4表达增加,LVEF、FS、IL-10、GSH、SOD水平及GPX4、Bcl2表达减少(P<0.05);与GDM组相比,L-Sal组、H-Sal组心肌组织病理变化减轻,空腹血糖、LVEF、FS、IL-10、GSH、SOD水平及GPX4、Bcl2表达增加,LVEDD、LVESD、HWI、CVF、CK-MB、cTnI、NT-proBNP、总铁离子含量、TNF-α、IL-6、MDA水平及AGE、RAGE、ACSL4表达减少(P<0.05);与H-Sal组相比,AGE组可以逆转上述指标变化,加重心肌组织病理变化;FBS-ZMI组能增强上述指标变化,减轻心肌组织病理变化。结论Sal可能抑制AGE-RAGE通路从而减轻GDM大鼠心肌损伤。Objective To investigate the effect of salidroside(Sal)on myocardial injury in gestational diabetes mellitus rats by regulating the dvanced glycation end products(AGE)-receptor for advanced glycation end-products(RAGE)pathway.Methods Ten healthy pregnant mice were randomly regarded as the healthy group.The GDM rat model was randomly separated into GDM group(gavage of physiological saline),L-Sal group(gavage of 25 mg/kg Sal),H-Sal group(gavage of 100 mg/kg Sal),AGE group(gavage of 100 mg/kg Sal+tail vein injection of 10 mg/kg AGE serum protein),and FBS-ZMI group(gavage of 100 mg/kg Sal+intraperitoneal injection of 150 mg/kg FBS-ZMI).The healthy group was gavage of physiological saline.Ultrasound imaging was applied to analyze left ventricular ejection fraction(LVEF),left ventricular short axis fraction shorting(FS),left ventricular end diastolic diameter(LVEDD),and left ventricular end systolic diameter(LVESD).The levels of creatine kinase isoenzyme(CK-MB),cardiac troponin I(cTnI)and N-terminal pro-brain natriuretic peptide(NT-proBNP)were detected by automatic biochemical analyzer,and heart mass index(HWI)was calculated.H-E staining and Masson staining were applied to observe the morphology of myocardial tissue.Enzyme linked immunosorbent assay(ELISA)was applied to detect levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),IL-10,malondialdehyde(MDA),glutathione(GSH),and superoxide dismutase(SOD).Ferrous zinc colorimetric method was applied to analyze the total iron ion content in tissues.Immunoblotting was applied to determine the expression of AGE,RAGE,glutathione peroxidase 4(GPX4),acyl-CoA synthetase 4(ACSL4),and Bcl2 proteins in tissues.Results Compared with the healthy group,the pathological changes of myocardial tissue in the GDM group were aggravated,the fasting blood glucose,LVEDD,LVESD,HWI,collagen volume fraction(CVF),CK-MB,cTnI,NT-proBNP,total iron ion content,TNF-α,IL-6,MDA levels,and AGE,RAGE,ACSL4 expression increased,the LVEF,FS,IL-10,GSH,SOD levels,and the GPX4 and Bcl2 expression decre

关 键 词：红景天苷 晚期糖基化终末产物-晚期糖基化终末产物受体通路 妊娠糖尿病大鼠 心肌损伤 

分 类 号：R714.256[医药卫生—妇产科学]