栀子苷调节AMPK/SIRT1/NF-κB信号通路对子痫前期大鼠氧化应激和炎症损伤的影响

Influence of geniposide on oxidative stress and inflammatory injury in preeclamptic rats by regulating AMPK/SIRT1/NF-κB signaling pathway

目的 探究栀子苷对子痫前期大鼠氧化应激和炎症损伤的影响及潜在机制。方法 96只孕鼠随机分为6组(16只/组):control组,Model组,GNP低、中、高剂量组,ComC抑制剂组。采用皮下注射L-精氨酸甲酯(L-NAME)建立PE模型。检测大鼠平均尾动脉压(MAP)、24 h尿蛋白、血尿素氮(BUN)水平及各组孕鼠平均子代的数目和体质量;H-E染色观察大鼠胎盘损伤;用试剂盒检测大鼠胎盘组织活性氧(ROS)、过氧化氢酶(CAT)、超氧化物歧化酶(SOD)、丙二醛(MDA)水平;酶联免疫吸附(ELISA)法检测大鼠胎盘组织炎性因子水平;Westernblot检测大鼠胎盘组织AMPK/SIRT1/NF-κB通路蛋白的表达。结果 Model组与control组相比、ComC抑制剂组与GNP高剂量组相比,大鼠MAP、24 h尿蛋白、BUN、炎性因子水平、MDA、ROS含量、p-NF-κB p65/NF-κB p65水平显著升高,SOD、CAT活性显著减弱、平均子代数和平均子代体质量、p-AMPK/AMPK、SIRT1蛋白表达水平显著降低(P<0.05);与Model组相比,GNP低、中、高剂量组大鼠MAP、24 h尿蛋白、BUN、炎性因子水平、MDA、ROS含量、p-NF-κB p65/NF-κB p65水平显著降低,SOD、CAT活性显著增强、平均子代数和平均子代体质量、p-AMPK/AMPK、SIRT1蛋白表达水平显著升高(P<0.05)。结论 GNP通过激活AMPK/SIRT1/NF-κB信号通路,抑制PE大鼠氧化应激和炎症损伤。

Objective To explore the effect of geniposide on oxidative stress and inflammatory injury in preeclampsia rats and its potential mechanism.Methods Ninety-six pregnant rats were randomly divided into 6 groups(16/group):control group,model group,GNP low,medium,high,dose group,ComC inhibitor group.PE model was established by subcutaneous injection of L-arginine methyl ester(L-NAME).The levels of mean tail arterial pressure(MAP),24 hour urine protein,blood urea nitrogen(BUN)and the number and weight of offspring in each group were detected;H-E staining was used to observe the injury of placenta in rats.The levels of reactive oxygen species(ROS),catalase(CAT),superoxide dismutase(SOD)and malondialdehyde(MDA)in rat placenta were detected by kit.The levels of inflammatory factors in placental tissue of rats were detected by enzyme-linked immunosorbent assay(ELISA).Western blot was used to detect the expression of AMPK/SIRT1/NF-κB pathway proteins in rat placenta.Results Model group compared with control group,ComC inhibitor group compared with GNP high dose group,The levels of MAP,24 h urinary protein,BUN,inflammatory factors,MDA,ROS and p-NF-κB p65/NF-κB p65 were significantly increased,the activities of SOD and CAT were significantly decreased,the average number of offspring and the average weight of offspring were significantly decreased,and the expression levels of p-AMPK/AMPK and SIRT1 protein were significantly decreased(P<0.05).Compared with Model group,the levels of MAP,24 h urine protein,BUN,inflammatory factors,MDA,ROS and p-NF-κB p65/NF-κB p65 were significantly decreased,the activities of SOD and CAT were significantly increased,the average number of offspring and the average weight of offspring,the expression levels of p-AMPK/AMPK and SIRT1 protein were significantly increased in GNP low,medium and high dose groups(P<0.05).Conclusion GNP inhibits oxidative stress and inflammatory injury in PE rats by activating AMPK/SIRT1/NF-κB signaling pathway.