基于血管紧张素Ⅱ/一氧化氮信号通路探究N-苄苯乙烯胺对妊娠期高血压模型大鼠的干预机制  

Exploring the intervention mechanism of N-benzylphenethylamine in rats with gestational hypertension based on the angiotensinⅡ/nitric oxide signaling pathway

作　　者：刘艳 刘晓夏 朱一麟[1] LIU Yan;LIU Xiaoxia;ZHU Yilin(Department of Obstetrics and Gynecology,Wuhan No.1 Hospital,Wuhan,Hubei 430022,China;Department of Obstetrics and Gynecology,Union Hospital Affiliated to Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei 430022,China)

机构地区：[1]武汉市第一医院妇产科,湖北武汉430022 [2]华中科技大学同济医学院附属协和医院妇产科,湖北武汉430022

出　　处：《安徽医药》2023年第6期1093-1097,共5页Anhui Medical and Pharmaceutical Journal

基　　金：国家自然科学基金资助项目(82001584)。

摘　　要：目的 基于血管紧张素Ⅱ/一氧化氮(AngⅡ/NO)信号通路探究N-苄苯乙烯胺(AG490)对妊娠期高血压(HDCP)模型大鼠的干预机制。方法 2021年1—5月,选取30只雌性大鼠,随机数字表法选取10只为正常组,其余20只建立HDCP模型,建模成功后使用随机数字表法分为HDCP组、AG490组各10只,AG490组大鼠腹腔注射5 mg/kg AG490,正常组、HDCP组大鼠腹腔注射等量生理盐水。检测三组大鼠血压、平均动脉压、24 h尿蛋白水平,免疫透射比浊法检测血肌酐、血尿素氮水平,酶联免疫吸附实验法检测炎症反应、氧化应激指标及AngⅡ、NO水平。检测三组大鼠胎盘质量及胎鼠情况,蛋白质印迹法检测内源性酪氨酸蛋白激酶2(JAK2)/信号传导和转录激活因子3(STAT3)/细胞因子信号转导抑制因子1(SOCS1)通路蛋白表达。结果HDCP组大鼠收缩压、舒张压、平均动脉压水平分别为(150.37±7.23)mmHg、(107.28±5.41)mmHg、(131.29±6.18)mmHg,AG490组大鼠收缩压、舒张压、平均动脉压水平分别为(121.25±5.91)mmHg、(86.22±4.26)mmHg、(97.35±5.11)mmHg,与HDCP组比较,AG490组大鼠血压、平均动脉压水平较低(P<0.05)。与HDCP组比较,AG490组大鼠24 h尿蛋白、血肌酐、血尿素氮水平较低(P<0.05)。与HDCP组比较,AG490组大鼠C反应蛋白(CRP)、白细胞介素-1β(IL-1β)、过氧化脂水平较低,过氧化氢酶(CAT)水平较高(P<0.05)。与HDCP组比较,AG490组大鼠胎盘质量、胎鼠体长、体质量较高(P<0.05)。HDCP组大鼠AngⅡ水平为(67.81±7.69)ng/L,NO水平为(41.17±5.39)moL/L,AG490组大鼠AngⅡ水平为(45.23±5.64)ng/L,NO水平为(54.62±6.57)moL/L,与HDCP组比较,AG490组大鼠AngⅡ水平较低,NO水平较高(P<0.05)。与HDCP组比较,AG490组大鼠JAK2、STAT3、SOCS1相对表达量较低(P<0.05)。结论 使用JAK2抑制剂AG490对HDCP模型大鼠进行干预,大鼠血压水平、肾功能明显改善,大鼠炎症反应、氧化应激减轻,胎鼠状况改善,大鼠内皮功能得到提升,JAKObjective To explore the intervention mechanism of N-benzylphenylstyreneamine(AG490)on gestational hypertension(HDCP)rats based on the angiotensinⅡ/nitric oxide(AngⅡ/NO)signaling pathway.Methods From January to May 2021,30 female rats were selected;10 were selected as the normal group by the random number table method,and the remaining 20 were established as HDCP models.After successful modeling,they were divided into 10 rats each in the HDCP group and AG490 group using the random number table method.Rats in the AG490 group were injected intraperitoneally with 5 mg/kg AG490,and rats in the normal group and HDCP group were injected intraperitoneally with equal amounts of saline.Blood pressure,mean arterial pressure and 24-h urinary protein,serum creatinine(Scr)and blood urea nitrogen(BUN)levels were determined by immunoturbidimetry,and inflammation response,oxidative stress index,AngⅡand NO levels were measured by enzyme-linked immunosorbent assay.The placental mass and fetal rats in the three groups were measured.Western blotting was used to detect the expression of the endogenous tyrosine kinase 2(JAK2)/signal transduction and transcription activator 3(STAT3)/cytokine signal transduction inhibitor 1(SOCS1)pathway.Results The systolic,diastolic and mean arterial pressure levels of the rats in the HDCP group were(150.37±7.23)mmHg,(107.28±5.41)mmHg and(131.29±6.18)mmHg,respectively,while the systolic,diastolic and mean arterial pressure levels of the rats in the AG490 group were(121.25±5.91)mmHg,(86.22±4.26)mmHg and(97.35±5.11)mmHg,respectively.Compared with the HDCP group,the blood pressure and mean arterial pressure levels were lower in the AG490 group of rats(P<0.05).Compared with the HDCP group,the 24-h urinary protein,Scr and BUN levels of rats in the AG490 group were lower(P<0.05).The levels of C-reactive protein(CRP),interleukin-1β(IL-1β)and lipid peroxide(LPO)were lower and the levels of catalase(CAT)were higher in the AG490 group than in the HDCP group(P<0.05).Compared with the HDCP group,the

关 键 词：高血压 妊娠性 肌酸酐 血管紧张素Ⅱ 转录激活因子3 过氧化脂质类 一氧化氮 肾功能 内皮功能 大鼠 Sprague-Dawley 

分 类 号：R714.246[医药卫生—妇产科学]