桑寄生总黄酮通过MEK/ERK通路对子痫前期大鼠肾脏的保护作用及对血管内皮功能的影响  

Study on Protective Effect of Total Flavonoids from Moraceae on Kidney and Vascu⁃lar Endothelial Function in Preeclampsia Rats Through MEK/ERK Pathway

作　　者：洪丽萍 尤云[2] 刘变玲[3] 张珂[4] HONG Li-ping;YOU Yun;LIU Bian-ling;ZHANG Ke(Department of Nephrology,Jinshui District General Hospital,Zhengzhou Henan 450003;Blood Purification Room,Af-filiated Hospital of Xinyang Vocational and Technical College,Xinyang Henan 464000;Department of Nephrology,Zhengzhou People′s Hospital,Zhengzhou Henan 450000;Department of Nephrology,the Second Affiliated Hospital of Zhengzhou University,Zhengzhou Henan 450000)

机构地区：[1]郑州市金水区总医院肾病科,河南郑州450003 [2]信阳职业技术学院附属医院血液净化室,河南信阳464000 [3]郑州人民医院肾内科,河南郑州450000 [4]郑州大学第二附属医院肾病科,河南郑州450000

出　　处：《世界中西医结合杂志》2023年第9期1745-1749,共5页World Journal of Integrated Traditional and Western Medicine

基　　金：2021年度河南省医学科技攻关计划联合共建项目(LHGJ20210400)。

摘　　要：目的探讨桑寄生总黄酮对子痫前期(Preeclampsia,PE)大鼠肾脏的保护作用及对血管内皮功能的影响,以及对丝裂原活化的细胞外信号调节激酶(Mitogen extracellular signal regulated kinase,MEK)/细胞外信号调节激酶(Extracellular signal regulated kinase,ERK)信号通路的调节作用。方法将60只健康清洁级成熟期受孕雌性大鼠按照随机数字表法分为正常组、模型组、桑寄生总黄酮低剂量组、桑寄生总黄酮中剂量组和桑寄生总黄酮高剂量组,每组各12只。从受孕第1天开始桑寄生总黄酮各剂量组分别给予90 mg/kg、180 mg/kg和360 mg/kg桑寄生总黄酮溶液灌胃,1次/d,连续21 d。从受孕第10天开始,除正常组外,其余组大鼠皮下注射左旋硝基精氨酸甲酯(L-NAME)125 mg/(kg·d),直至妊娠第19天。检测各组大鼠血压和24 h尿蛋白水平,放射免疫法测定血清前列腺环素(Vascular endothelial growth factor,VEGF)、血栓烷(Thromboxane B2,TXB2)和血浆内皮素-1(En⁃dothelin-1,ET-1)水平,采用ELISA法检测白介素-1β(Interleukin-1β,IL-1β)、白介素-6(Interleukin-6,IL-6)和肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)水平,HE染色观察肾组织病理损伤,蛋白印迹法检测p-MEK1/2/MEK1/2和p-ERK1/2/ERK1/2比值。结果正常组大鼠肾小管和肾小球结构完整,未见空泡化;模型组大鼠可见肾小管上皮细胞出现空泡化,可见上皮细胞脱落;桑寄生总黄酮低、中和高剂量组大鼠肾组织病理改变较模型组减轻。与正常组比较,模型组大鼠血压和24 h尿蛋白水平、TXB2和ET-1水平以及IL-1β、IL-6和TNF-α水平升高,VEGF水平以及p-MEK1/2/MEK1/2和p-ERK1/2/ERK1/2比值降低,差异有统计学意义(P<0.05);与模型组比较,桑寄生总黄酮低、中和高剂量组大鼠血压和24 h尿蛋白水平、TXB2和ET-1水平以及IL-1β、IL-6和TNF-α水平降低,VEGF水平以及p-MEK1/2/MEK1/2和p-ERK1/2/ERK1/2比值升高,差异有统计学意义(P<0.05),其中以桑寄生总黄酮�Objective To investigate the protective effect of total flavonoids from Moraceae on the kidney of pre⁃eclampsia(PE)rats,the effect on vascular endothelial function,and the regulation of mitogen-activated extracellular signal-regulated kinase(MEK)/extracellular signal-regulated kinase(ERK)signaling pathway.Methods According to the random number table method,60 pregnant female rats who were healthy,clean,and mature were randomly divided into nor⁃mal group,model group,as well as low,medium,and high dose groups of total flavonoids from Moraceae,with 12 rats in each ournal of Integrated Traditional and Western Medicine 2023,Vol.18,No.9 group.From the first day of pregnancy,each group of total flavonoids from Moraceae was given a total flavonoid solution of 90,180,and 360 mg/kg by intragastric administration once a day,for 21 consecutive days.From the 10th day of pregnan⁃cy,except for the normal group,rats in other groups were subcutaneously injected with l-nitroarginine methyl ester(L-NAME)of 125 mg/(kg·d)until the 19th day of pregnancy.Blood pressure and 24-h urinary protein levels were detec⁃ted.Vascular endothelial growth factor(VEGF),thromboxane(TXB2),and plasma endothelin-1(ET-1)levels were de⁃termined by radioimmunoassay.Interleukin-1β(IL-1β),IL-6,and tumor necrosis factor-α(TNF-α)levels were de⁃tected by ELISA.The ratio of p-MEK1/2/MEK1/2 and p-ERK1/2/ERK1/2 was detected by western blot.Results In the normal group,the renal tubules and glomerulus were intact without vacuolation.Vacuolization and exfoliation of renal tubule epithelial cells were observed in the model group.The pathological changes of kidney tissue in the low,medium,and high dose groups of total flavonoids from Moraceae were less than those in the model group.Compared with the normal group,the levels of blood pressure,24-h urinary protein,TXB2,ET-1,IL-1β,IL-6,and TNF-αin the model group were increased,while the levels of VEGF and the ratio of p-MEK1/2/MEK1/2 and p-ERK1/2/ERK1/2 were decreased(P<0.05).Compared with the model gro

关 键 词：子痫前期 血管内皮损伤 桑寄生总黄酮 MEK/ERK信号通路 

分 类 号：R285.5[医药卫生—中药学]