【摘要】 目的 探讨苦参碱对妊娠高血压(PIH)大鼠内皮损伤及酪氨酸蛋白激酶2/信号转导子和转录激活子3/细胞因子信号转录抑制因子1(JAK2/STAT3/SOSC1)信号通路的影响。方法 将60只孕鼠随机分成正常对照组、模型对照组、低剂量苦参碱组、高剂量苦参碱组、硫酸镁组，每组12只。正常对照组之外的各组孕鼠在妊娠第12天通过灌胃50 mg/kg亚硝基左旋精氨酸甲酯构建PIH大鼠模型。在妊娠第16天，低、高剂量苦参碱组分别灌胃50、100 mg/kg苦参碱，硫酸镁组灌胃100 mg/kg硫酸镁，正常对照组和模型对照组则灌胃等体积的生理盐水。分别使用大鼠无创血压计和考马斯亮蓝法检测各组孕鼠妊娠第16天(给药前)、第17天、第21天的尾动脉血压及24 h尿蛋白含量；酶联免疫分析试剂盒检测血清中超氧化物歧化酶(SOD)、丙二醛(MDA)、肿瘤坏死因子α(TNF-α)、白细胞介素(IL)-6、IL-10、内皮素(ET)、血栓素B2(TXB2)、一氧化氮(NO)、6酮前列腺素F1α(6-keto-PGF1α)水平；蛋白免疫印迹法检测大鼠胎盘组织中JAK2、p-JAK2、STAT3、p-STAT3、SOSC1蛋白表达水平。结果 妊娠第17、21天，模型对照组孕鼠血压、24 h尿蛋白含量明显高于正常对照组(P<0.05),低、高剂量苦参碱组孕鼠血压、24 h尿蛋白含量明显比模型对照组低(P<0.05)。与正常对照组比较，模型对照组大鼠血清中SOD、IL-10、NO和6-keto-PGF1α水平降低，MDA、TNF-α、IL-6、ET和TXB2以及胎盘组织中p-JAK2/JAK2、p-STAT3/STAT3、SOSC1蛋白水平升高(P<0.05);与模型对照组相比，低、高剂量苦参碱组SOD、IL-10、NO和6-keto-PGF1α依次增加，MDA、TNF-α、IL-6、ET和TXB2以及胎盘组织中p-JAK2/JAK2、p-STAT3/STAT3、SOSC1蛋白水平依次降低(P<0.05);与硫酸镁组相比，高剂量苦参碱组上述指标均无明显改变(P>0.05)。结论 苦参碱降低PIH模型大鼠血压、尿蛋白含量、炎症反应及氧化应激水平，抑制JAK2、STAT3磷酸化及SOSC1蛋白表达，进而缓解PIH大鼠内皮损伤。更多还原

【Abstract】 Objective To investigate the effect of matrine on endothelial injury and the Janus-activated kinase 2/signal transducer and activator of transcription 3/suppressor of cytokine signaling-1(JAK2/STAT3/SOSC1) signaling pathway in rats with pregnancy-induced hypertension(PIH). Methods Sixty pregnant rats were randomly separated into normal control group, model control group, low dose matrine group, high dose matrine group and magnesium sulfate group, with 12 rats in each group. Pregnant rats in each group except the normal control group were intragastrically administered 50 mg/kg nitroso-L-arginine methyl ester on day 12 of pregnancy to establish a PIH rat model. On day 16 of pregnancy, low and high dose matrine groups were administered intragastrically with 50 and 100 mg/kg matrine, respectively, the magnesium sulfate group was administered intragastrically with 100 mg/kg magnesium sulfate, and normal and model control groups were administered intragastrically with an equal volume of saline. A rat non-invasive sphygmomanometer and Coomassie blue staining were used to assess tail artery blood pressure and the 24 h urine protein content of pregnant rats in each group on day 16(before administration), day 17 and day 21 of pregnancy. Enzyme-linked immunoassays were used to determine the levels of superoxide dismutase(SOD), malondialdehyde(MDA), tumor necrosis factor-α(TNF-α), interleukin(IL)-6, IL-10, endothelin(ET), thromboxane B2(TXB2), nitric oxide(NO), and 6-keto-prostaglandin F1α(6-keto-PGF1α). Western blot was used to measure JAK2, p-JAK2, STAT3, p-STAT3 and SOSC1 protein expression in rat placental tissue. Results On the days 17 and 21 of pregnancy, blood pressure and the 24 h urine protein content of pregnant rats in the model control group were significantly higher than those in the normal control group(P<0.05), and blood pressure and the 24 h urine protein content of pregnant rats in low and high dose matrine groups were significantly lower than those in the model control group(P<0.05). Compared with the normal control group, serum levels of SOD, IL-10, NO and 6-keto-PGF1α in the model control group were lower, and MDA, TNF-α, IL-6, ET and TXB2 levels and p-JAK2/JAK2, p-STAT3/STAT3 and SOSC1 protein expression in placental tissue were higher(P<0.05). Compared with the model control group, SOD, IL-10, NO and 6-keto-PGF1α in low and high dose matrine groups were increased sequentially, and MDA, TNF-α, IL-6, ET and TXB2 levels and p-JAK2/JAK2, p-STAT3/STAT3, and SOSC1 protein expression in placental tissue were decreased sequentially(P<0.05). Compared with the magnesium sulfate group, the above indicators in the high dose matrine group showed no significant changes(P>0.05). Conclusions Matrine decreases blood pressure, urinary protein content, inflammatory responses, and oxidative stress, inhibits JAK2 and STAT3 phosphorylation and SOSC1 protein expression, and then alleviates endothelial injury in PIH rats更多还原