摘要
目的 探究根皮素是否可通过调节分泌型糖蛋白(Wnt)/β-连环蛋白(β-catenin)信号通路缓解妊娠期高血压大鼠的血压、血管内皮损伤及炎症反应。方法 将7~8周龄受孕雌性SD大鼠50只随机分为对照组、妊娠期高血压组(模型组)、根皮素低剂量组(150 mg/kg)、根皮素高剂量组(300 mg/kg)、根皮素高剂量+分泌型卷曲相关蛋白1(sFRP1,Wnt/β-catenin信号通路抑制剂,1μg/kg)组,每组10只,妊娠第15~20天给予根皮素处理。检测大鼠受孕后第12、15、19、21天的动脉收缩压和24 h尿蛋白;采用酶联免疫吸附试验(ELISA)法检测血清一氧化氮、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和白细胞介素-10(IL-10)水平;采用苏木精-伊红(HE)染色观察胎盘组织形态变化;检测胎盘组织中丙二醛含量、超氧化物歧化酶(SOD)和过氧化氢酶(CAT)活性;采用Western-blot法检测胎盘组织中内皮素-1、内皮型一氧化氮合酶(eNOS)、Wnt、β-catenin、B细胞淋巴瘤2(Bcl-2)和Bcl-2关联X蛋白(Bax)表达水平。结果 大鼠受孕后第21天,与对照组相比,模型组大鼠胎盘组织有明显损伤,收缩压,24 h尿蛋白,血清内皮素-1、TNF-α、IL-6水平,胎盘组织中内皮素-1蛋白表达、丙二醛含量、Bax蛋白表达水平升高,血清一氧化氮和IL-10水平,胎盘组织中eNOS蛋白表达,SOD和CAT活性,Wnt、β-catenin、Bcl-2蛋白表达水平降低(均P<0.05);与模型组相比,根皮素低剂量组和根皮素高剂量组大鼠胎盘组织损伤明显减轻,收缩压,24 h尿蛋白,血清内皮素-1、TNF-α、IL-6水平,胎盘组织中内皮素-1蛋白表达、丙二醛含量、Bax蛋白表达水平降低,血清一氧化氮和IL-10水平,胎盘组织中eNOS蛋白表达,SOD和CAT活性,Wnt、β-catenin、Bcl-2蛋白表达水平升高(P<0.05);sFRP1可减弱根皮素对妊娠期高血压大鼠血管内皮的保护作用(P<0.05)。结论 根皮素可降低妊娠期高血压大鼠的血压、炎症和氧化应激,改善胎盘组织和血管内皮损伤,可能与激活Wnt/β-catenin信号通路有关。
Objective To explore whether phloretin(PHL)can regulate Wnt/β-catenin signaling pathway to alleviate blood pressure,vascular endothelial injury and inflammation in rats with gestational hypertension.Methods Fifty pregnant female SD rats aged 7 to 8 weeks were randomly divided into control group,gestational hypertension group(model group),PHL low-dose group(150 mg/kg),PHL high-dose group(300 mg/kg),and PHL high-dose+secreted frizzled-related protein 1(sFRP1,Wnt/β-catenin signaling pathway inhibitor,1μg/kg)group,with 10 rats in each group.Rats were treated with PHL on the 15th to 20th day of pregnancy.Arterial systolic blood pressure and 24 h urinary protein were measured at the 12th,15th,19th and 21th day after conception.Enzyme-linked immunosorbent assay(ELISA)was used to detect serum levels of nitric oxid(NO),tumor necrosis factorα(TNF-α),interleukin-6(IL-6),and interleukin-10(IL-10).Hematoxylin and eosin(HE)staining was used to observe changes in placental tissue morphology.The malondialdehyde(MDA)content,superoxide dismutase(SOD)and catalase(CAT)activities in placental tissue were detected.Western-blot was used to detect the expression levels of endothelin-1(ET-1),endothelial nitric oxide synthase(eNOS),Wnt,β-catenin,B-cell lymphoma-2(Bcl-2),and Bcl-2-associated X(Bax)proteins in placental tissue.Results At the 21th day after conception,compared with the control group,in the model group,the placental tissue of rats was significantly damaged,the systolic blood pressure,24-hour urine protein,serum ET-1,TNF-αand IL-6 levels,ET-1 protein expression,MDA content,and Bax protein expression in placental tissue were significantly increased,while the serum NO and IL-10 levels,eNOS protein expression in placental tissue,SOD and CAT activities,Wnt,β-catenin,and Bcl-2 protein expression were significantly decreased(all P<0.05).Compared with the model group,in PHL low-dose group and PHL high-dose group,the damage of placental tissue was significantly reduced,the systolic blood pressure,24-hour urine protein,serum ET-1,TNF-αand IL-6 levels,ET-1 protein expression,MDA content,and Bax protein expression in placental tissue were significantly decreased,while the serum NO and IL-10 levels,eNOS protein expression in placental tissue,SOD and CAT activities,Wnt,β-catenin,and Bcl-2 protein expression were significantly increased(all P<0.05).SFRP1 can reduce the protective effect of PHL on vascular endothelium in rats with gestational hypertension(P<0.05).Conclusion PHL can reduce blood pressure,inflammation and oxidative stress,and improve the damage of placental tissue and vascular endothelial in rats with gestational hypertension,which may be related to the activation of the Wnt/β-catenin signaling pathway.
作者
叶海琼
丁洪梅
YE Haiqiong;DING Hongmei(Department of Obstetrics,Affiliated Hospital of Southwest Medical University,Luzhou,Sichuan 646000,China)
出处
《中华高血压杂志(中英文)》
北大核心
2025年第1期75-81,共7页
Chinese Journal of Hypertension
基金
2021年四川省医学会(青年创新)科研课题项目(S21102)。
