子痫前期大鼠胎盘细胞自噬水平变化及黄芩苷的干预作用

目的：研究胎盘细胞自噬在大鼠子痫前期发生发展中的作用及黄芩苷的干预作用。方法：48只Wistar孕鼠随机分成4组，每组12只。正常妊娠组大鼠自妊娠13 d起连续皮下注射0.9%氯化钠溶液1.5 mL/d至妊娠21 d；子痫前期组大鼠自妊娠13 d起连续皮下注射亚硝基左旋精氨酸甲酯100 mg/（kg·d）至妊娠21 d；黄芩苷组和自噬抑制组大鼠除了子痫前期组处理外，同时从妊娠16 d起，每天分别给予腹腔注射黄芩苷50 mg/（kg·d）和3-甲基腺嘌呤15 mg/（kg·d）至妊娠21 d。在妊娠21 d测量大鼠尾动脉血压及24 h尿蛋白水平，Western blot测定胎盘细胞Beclin 1、LC3-II和P62蛋白表达水平。结果：子痫前期组较正常妊娠组大鼠胎盘细胞Beclin 1和LC3-II蛋白表达水平显著增高（P ＜0.05），尾动脉收缩压和舒张压及24 h尿蛋白水平显著升高（P ＜0.05），而P62蛋白表达水平显著减少（P ＜0.05）；黄芩苷组和自噬抑制组较子痫前期组大鼠胎盘细胞Beclin 1和LC3-II蛋白表达水平显著减少（P ＜0.05），尾动脉收缩压和舒张压及24 h尿蛋白水平显著减少（P ＜0.05），而P62蛋白表达水平显著升高（P ＜0.05）。结论：胎盘细胞自噬可能参与大鼠子痫前期的发生发展过程，而黄芩苷腹腔注射可显著抑制子痫前期大鼠胎盘细胞自噬，从而发挥对子痫前期的治疗作用。

Autophagy of placental cells in the pathogenesis of preeclampsia rats and the interventional effect of baicalin

Objective: To discover the role of autophagy of placental cells in the occurrence and development of rat preeclampsia and the interventional effect of baicalin on it. Methods: Totally 48 pregnant Wistar rats were randomly divided into four groups, with 12 in each. Rats in normal pregnancy group were administered with a subcutaneous injection of 1.5 mL normal sodium from Day 13 of pregnancy until Day 21. Rats in preeclampsia group were given a subcutaneous injection of Nitro L Arginine Methyl Ester at 100 mg/kg per day from Day 13 of pregnancy until Day 21. Rats in baicalin group and autophagy inhibition group were treated the same as in preeclampsia group but simultaneously given intraperitoneally injection with baicalin at 50 mg/kg and 3-methyladenine respectively at 15 mg/kg per day from Day 16 of pregnancy until Day 21. At pregnant day 21, the rat tail artery blood pressure and 24 h urine protein level were measured and Western blot was used to determine the expression level of Beclin1, LC3-II and P62 proteins in placental cells. Results: Compared with normal pregnancy group, the expression level of Beclin 1 and LC3-II proteins in placental cells of rats was significantly elevated in preeclampsia group (P<0.05), and tail arterial systolic and diastolic blood pressures and 24 h urine protein level were substantially raised (P<0.05), while expression level of P62 protein was markedly decreased (P<0.05);when compared with preeclampsia group, the expression level of Beclin 1 and LC3-II proteins in placental cells of rats were significantly declined in baicalin group and autophagy inhibition group (P<0.05), and tail arterial systolic and diastolic blood pressures and 24 h urine protein level were substantially decreased (P<0.05), while the expression level of P62 protein was markedly increased (P<0.05). Conclusion: Autophagy of placental cellsmay be implicated in the occurrence and development of rat preeclampsia, and intraperitoneal injection of baicalin can obviously depress autophagy of placental cells of preeclampsia rats, subsequently exerting its therapeutic effect on preeclampsia.