萝卜硫素调节腺苷酸活化蛋白激酶/沉默信息调节器1/过氧化物酶体增殖活化受体γ辅助活化因子1α信号通路对妊娠高血压大鼠妊娠结局的影响  

Impact of sulforaphane on the pregnancy outcome of gestational hypertensive rats by regulating adenylate-activated protein kinase/silent information regulator 1/peroxisome proliferator-activated receptor gamma coactivator 1α signaling pathway

作　　者：马合红[1] 侯秀真 冯妙肖 张俊峰[1] MA Hehong;HOU Xiuzhen;FENG Miaoxiao;ZHANG Junfeng(Obstetrics Department,Cangzhou Central Hospital,Cangzhou,Hebei 061001,China)

机构地区：[1]沧州市中心医院产科,河北沧州061001

出　　处：《安徽医药》2024年第4期666-672,I0001,共8页Anhui Medical and Pharmaceutical Journal

基　　金：沧州市科技计划项目(131302110)。

摘　　要：目的 探究萝卜硫素(SFN)通过调节腺苷酸活化蛋白激酶(AMPK)/沉默信息调节器1(SIRT1)/过氧化物酶体增殖活化受体γ辅助活化因子1α(PGC-1α)信号通路对妊娠期高血压疾病(HDP)大鼠妊娠结局的影响。方法 2021年3月至2022年6月,70只雌性大鼠受孕后分为对照组、HDP组、SFN-L组(SFN 5 mg/kg)、SFN-M(SFN 15 mg/kg)、SFN-H(SFN 30 mg/kg)、硫酸镁组(硫酸镁注射液100 mg/kg)、Compound C组(SFN 30 mg/kg+AMPK抑制剂Compound C 0.25 mg/kg),各组10只。在妊娠第13天起除对照组,其余各组妊娠大鼠尾静脉注射7 mg/kg L-NAME,连续注射4 d,建立HDP大鼠模型,对照组大鼠尾静脉注射0.9%氯化钠溶液。从造模成功后第1天(妊娠第17天)起,各给药组注射相应剂量的药物,对照组、HDP组注射0.9%氯化钠溶液,连续给药至妊娠第20天。检测妊娠第17天和第20天各组大鼠尾动脉压和24 h尿蛋白定量水平;试剂盒法检测大鼠血肌酐(SCr)和血尿素氮(BUN)水平;观察检测大鼠妊娠结局指标;HE染色观察胎盘组织和肾脏组织病理情况;蛋白质印迹法检测胎盘组织可溶性血管内皮生长因子受体-1(sFLT-1)、胎盘生长因子(PLGF)、内皮型一氧化氮合酶(eNOs)、磷酸化eNOs(peNOs)、磷酸化AMPK(p-AMPK)、AMPK、SIRT1、PGC-1ɑ蛋白水平。结果 HDP组大鼠血压[(152.52±4.79)mmHg比(101.63±4.15)mmHg]、24 h尿蛋白定量水平[(679.38±64.32)mg/L比(123.17±20.19)mg/L]、胎鼠病死率[(28.57±2.08)%比(0.96±0.11)%]、血清SCr和BUN水平、胎盘组织sFLT-1表达水平高于对照组(P<0.05),而胎鼠质量[(2.32±0.19)g比(4.75±0.43)g]、产仔数[(11.70±0.69)个比(7.10±0.57)个]、胎盘质量[(0.32±0.06)g比(0.58±0.12)g]、胎盘组织PLGF、p-eNOs、p-AMPK、SIRT1和PGC-1ɑ蛋白表达低于对照组(P<0.05),另外,HDP大鼠胎盘组织绒毛数量减少,胎盘结构缩小,部分绒毛显示纤维蛋白样坏死,肾脏组织内肾小球数目减少,结构异常;SFN-L组、SFN-M组、SFN-H组和硫酸镁组大鼠血压Objective To explore the impact of sulforaphane(SFN)on pregnancy outcome in hypertensive disorder of pregnancy(HDP)rats through regulation of adenylate-activated protein kinase(AMPK)/silent information regulator 1(SIRT1)/peroxisome proliferator-activated receptor gamma coactivator 1α(PGC-1α)signaling pathway.Methods From March 2021 to June 2022,after conception,70 female rats were grouped into control group,HDP group,SFN-L group(SFN 5 mg/kg),SFN-M(SFN 15 mg/kg),SFN-H(SFN 30 mg/kg),magnesium sulfate group(magnesium sulfate 100 mg/kg),Compound C group(SFN 30 mg/kg+AMPK inhibitor Compound C 0.25 mg/kg),10 rats in each group.From the 13th day of pregnancy,except the control group,the other pregnant rats were injected with 7 mg/kg L-NAME through the tail vein for 4 consecutive days to establish the HDP rat model,while the rats in the control group were injected with normal saline through the tail vein.From the first day after successful modeling(the 17th day of pregnancy),each administration group was injected with the corresponding dose of drugs,and the control group and HDP group were injected with normal saline,and the administration continued until the 20th day of pregnancy.The tail arterial pressure and 24 h urine protein quantitative level of rats in each group were detected on the 17th and 20th day of pregnancy.Kit method was used to detect the levels of serum creatinine(SCr)and blood urea nitrogen(BUN)in rats;the pregnancy outcome indicators of rats were observed and detected;HE staining was used to observe the pathological conditions of placental tissue and kidney tissue;Western blotting was used to detect the protein levels of soluble vascular endothelial growth factor recepter-1(sFLT-1),placental growth factor(PLGF),endothelial nitric oxide synthase(eNOs),phosphorylated eNOs(p-eNOs),phosphorylated AMPK(p-AMPK),AMPK,SIRT1 and PGC-1αin placenta tissue.Results The blood pressure[(152.52±4.79)mmHg vs.(101.63±4.15)mmHg],24 h urine protein quantitative level[(679.38±64.32)mg/L vs.(123.17±20.19)mg/L)],fetal

关 键 词：高血压 妊娠性 萝卜硫素 AMPK/SIRT1/PGC-1ɑ信号通路 大鼠 Sprague-Dawley 妊娠结局 

分 类 号：R285.5[医药卫生—中药学]