夏枯草提取物对子痫前期大鼠氧化应激损伤及AMPK/p62/Nrf2通路的影响  

Effect of Prunella vulgaris extract on oxidative stress damage and AMPK/p62/Nrf2 pathway in preeclamptic rats

作　　者：刘宝峰[1] 昝双江[1] 骆伟舜 韩梅 LIU Baofeng;ZAN Shuangjiang;LUO Weishun;HAN Mei(Department of Pharmacy,Tianjin Municipal Fourth Central Hospital,Tianjin300140,China;Department of Internal Medicine,Xiaodian Community Health Service Center,Tianjin 300251,China)

机构地区：[1]天津市第四中心医院药剂科,300140 [2]天津市小淀社区卫生服务中心内科,300251

出　　处：《重庆医学》2022年第11期1824-1828,共5页Chongqing medicine

基　　金：天津市科技发展计划项目(2018-SHGY-1917)。

摘　　要：目的探讨夏枯草提取物(PVE)对子痫前期(PE)大鼠氧化应激损伤及腺苷酸蛋白活化激酶(AMPK)/核孔糖蛋白62(p62)/核因子E2相关因子2(Nrf2)通路的影响。方法以皮下注射左旋硝基精氨酸甲酯的方法诱导构建60只PE大鼠模型,将其分为模型组、PVE低剂量(6 mg/kg)组、PVE中剂量(12 mg/kg)组、PVE高剂量(24 mg/kg)组、硫酸镁(30 mg/kg)组,每组12只,另取12只妊娠大鼠皮下注射等剂量生理盐水,作为对照组,以药物分组干预处理后,测量各组大鼠妊娠晚期平均动脉压(MAP)、24 h尿蛋白及血尿素氮(BUN)水平,评测各组大鼠妊娠结局,比较其平均子代数目及平均子代体重;以相应试剂盒测量各组大鼠胎盘组织活性氧(ROS)、过氧化氢酶(CAT)及丙二醛(MDA)水平;以Western blot检测各组大鼠胎盘组织AMPK/p62/Nrf2通路蛋白表达。结果与对照组比较,模型组大鼠平均子代数目及平均子代体重、胎盘组织CAT水平、p-AMPK/AMPK、p62及Nrf2蛋白表达水平明显降低(P<0.05),妊娠晚期MAP、24 h尿蛋白及BUN水平、胎盘组织ROS及MDA水平明显升高(P<0.05);与模型组比较,PVE低、中、高剂量组及硫酸镁组大鼠平均子代数目及平均子代体重、胎盘组织CAT水平、p-AMPK/AMPK、p62及Nrf2蛋白表达水平均升高(P<0.05),妊娠晚期MAP、24 h尿蛋白及BUN水平、胎盘组织ROS及MDA水平均降低(P<0.05),且PVE各组呈剂量依赖性(P<0.05);与硫酸镁组比较,PVE高剂量组大鼠各指标差异无统计学意义(P>0.05)。结论PVE可激活AMPK/p62/Nrf2通路,去除氧自由基,抑制PE大鼠氧化应激反应,降低血压、减轻蛋白尿症状,改善其妊娠结局促使子代存活。Objective To study the effects of Prunella vulgaris extract(PVE)on the oxidative stress damage and adenylate-activated protein kinase(AMPK)/p62/nuclear factor E2-related factor2(Nrf2)pathway in preeclampsia(PE)rats.Methods Sixty PE rat models were established by induction of L-nitroarginine methyl ester subcutaneous injection,and the rats were randomly divided into the model group,low-dose PVE(6 mg/kg)group,middle-dose PVE(12 mg/kg)group,high-dose PVE(24 mg/kg)group and magnesium sulfate(30 mg/kg)group,12 cases in each group.Other 12 pregnant rats were subcutaneously injected by the same dose of normal saline as the control group.After intervention treatment with the medication grouping,the mean arterial pressure(MAP)in the late pregnant rats was measured,24 h urine protein and blood urea nitrogen(BUN)contents during the late pregnant rats in each group were measured,and the pregnancy outcome of each group was evaluated,and the average number of offspring and average weight of offspring were compared among the groups;the levels of reactive oxygen species(ROS),catalase(CAT)and malondialdehyde(MDA)in rat placental tissues in each group were measured with the kit;the expression of AMPK/p62/Nrf2 pathway protein in rat placental tissue in each group was detected by Western blot.Results Compared with the control group,the average number of offspring and average weight of offspring,the level of CAT in placental tissue,protein expression levels of p-AMPK/AMPK,p62 and Nrf2 in the model group were significantly reduced(P<0.05),the levels of MAP,24h urine protein and BUN in the late pregnant period,and levels of ROS and MDA in placental tissue were significantly increased(P<0.05);compared with the model group,the average number of offspring and average weight of offspring,the level of CAT in placental tissue,the protein expression levels of p-AMPK/AMPK,p62 and Nrf2 in the drug intervention groups were significantly increased(P<0.05),the MAP,24h urine protein and BUN levels in the late pregnancy,and levels of ROS and MDA in

关 键 词：夏枯草提取物 子痫前期 氧化应激 腺苷酸蛋白活化激酶/核孔糖蛋白62/核因子E2相关因子2通路 

分 类 号：R285.5[医药卫生—中药学]