基于Gadd45α-p38MAPK通路研究葛根素对子痫前期大鼠胎盘氧化应激的影响及作用机制

Study on the Effect and Mechanism of Puerarin on Placenta Oxidative Stress in Rats with Preeclampsia Based on Gadd45α-p38MAPK Pathway

目的 探讨葛根素(puerarin,Pue)通过Gadd45α-p38MAPK通路对子痫前期大鼠的影响及作用机制。方法 孕鼠随机分为对照组、模型组、Pue低剂量组、Pue高剂量组、阳性药物组。除对照组外,其余各组自孕7 d开始,皮下注射L-精氨酸甲酯(L-argininemethylester,L-NAME)诱导子痫前期。孕14d开始,Pue低剂量组、Pue高剂量组分别按40,80 mg·kg–1体质量腹腔注射Pue注射液,阳性药物组按80 mg·kg–1体质量腹腔注射硫酸镁,对照组和模型组腹腔注射等量生理盐水。分别于孕13,17,21 d测量大鼠尾动脉压和24 h尿蛋白;称取胎盘质量和仔鼠体质量;检测胎盘组织中活性氧(reactiveoxygenspecies,ROS)、丙二醛(malondialdehyde,MDA)和一氧化氮(nitricoxide,NO)浓度;Westernblotting检测胎盘组织相关蛋白表达。结果 与模型组比较,Pue低剂量组、Pue高剂量组和阳性药物组孕17,21 d尾动脉压和24 h尿蛋白含量、胎盘组织中ROS、MDA水平降低,胎盘质量、胎盘组织中NO水平升高,胎盘组织中Gadd45α、p-p38MAPK蛋白相对表达量降低(P<0.05)。结论 Pue对子痫前期大鼠具有降血压作用,可减少氧化应激损伤,改善相关症状,可能通过抑制Gadd45α/p38MAPK信号通路发挥作用。

OBJECTIVE To explore the effect of puerarin(Pue) on preeclampsia rats through Gadd45α-p38 MAPK pathway and its mechanism.METHODS Pregnant rats were randomly divided into control group,model group,Pue low-dose group,Pue high-dose group,and positive drug group.Except for the control group,the other groups received subcutaneous injection of L-arginine methyl ester(L-NAME) from the 7th day of pregnancy to induce preeclampsia.From the 14th day of pregnancy,Pue low-dose group and Pue high-dose group were injected intraperitoneally with Pue injection at 40,80 mg·kg–1respectively according to body weight,and the positive drug group was injected with magnesium sulfate intraperitoneally at 80 mg·kg–1 according to body weight,the same amount of saline was injected intraperitoneally in control group and model group.Rats tail artery pressure and 24 h urine protein on 13th,17th,and 21st gestation days were measured.The weight of placenta and offspring were weighed,reactive oxygen species(ROS),malondialdehyde(MDA) and nitric oxide(NO) were detected.Western blotting was used to detect the expression of placental tissue-related proteins.RESULTS Compared with the model group,17,21 d tail artery pressure and 24 h urine protein content,ROS and MDA levels in placental tissue decreased,placenta weight,NO levels in placental tissue increased,Gadd45α and p-p38MAPK protein expression in placental tissue decreased in Pue low-dose group,Pue high-dose group and positive drug group(P<0.05).CONCLUSION Pue has a hypotensive effect on preeclampsia rats,can reduce oxidative stress damage and improve related symptoms,and may play an effect by inhibiting Gadd45α/p38MAPK signaling pathway.