高良姜素调节IL-6/STAT3信号通路对子痫前期大鼠免疫炎症反应的影响  

Impacts of galangin on immune inflammatory response in preeclampsia rats by regulating IL-6/STAT3 signaling pathway

作　　者：刘东芳 王毅 韩森吉 孙冲 孙宁宁 龙天舒 LIU Dongfang;WANG Yi;HAN Senji;SUN Chong;SUN Ningning;LONG Tianshu(Department of Obstetrics,Zibo First Hospital,Zibo 255200,China)

机构地区：[1]淄博市第一医院产科,淄博255200

出　　处：《中国免疫学杂志》2024年第12期2513-2517,2524,共6页Chinese Journal of Immunology

基　　金：山东省中医药科技项目(2021H30)。

摘　　要：目的:初步探讨高良姜素(Gal)调节IL-6/信号转导与转录激活子3(STAT3)信号通路对子痫前期(PE)大鼠免疫炎症反应的影响。方法:通过孕鼠皮下注射L-精氨酸甲酯(L-NAME 125 mg/kg)建立PE模型,造模成功后,随机分为Model组、Gal低、中、高剂量组(10、30、60 mg/kg)、激活剂组(60 mg/kg Gal^(+)0.05 mg/kg IL-6/STAT3通路激活剂rIL-6),随机选取12只同期孕鼠作为control组,各组灌胃并腹腔注射相应药物,1次/d,连续1周。采用血压测试仪、全自动生化分析仪测量大鼠妊娠晚期平均尾动脉压(MAP)及24 h尿蛋白和血尿素氮(BUN)水平;计算各组孕鼠平均子代的数目和体质量,分析妊娠结局;HE染色观察大鼠胎盘组织病理损伤;ELISA检测各组大鼠胎盘组织中IL-6、IL-1β、TNF-α水平;流式细胞术检测大鼠外周血中T淋巴细胞比例;Western blot检测大鼠胎盘组织中IL-6/STAT3通路蛋白表达。结果:与control组相比,Model组大鼠MAP、24 h尿蛋白、BUN、IL-6、IL-1β、TNF-α水平、CD8^(+)T细胞、IL-6、p-STAT3/STAT3蛋白表达水平显著升高,胎盘组织受损严重,平均子代数和平均子代体质量、CD3^(+)T、CD4^(+)T、CD4^(+)/CD8^(+)T细胞比例减少(P<0.05);与Model组相比,Gal低、中、高剂量组大鼠MAP、24 h尿蛋白、BUN、IL-6、IL-1β、TNF-α、CD8^(+)T细胞、IL-6、p-STAT3/STAT3蛋白表达水平显著降低,胎盘组织受损减轻,平均子代数和平均子代体质量、CD3^(+)T、CD4^(+)T、CD4^(+)/CD8^(+)T细胞比例增加(P<0.05);与Gal高剂量组相比,激活剂组大鼠MAP、24 h尿蛋白、BUN、IL-6、IL-1β、TNF-α、CD8^(+)T细胞、IL-6、p-STAT3/STAT3蛋白表达水平显著升高,胎盘组织受损加重,平均子代数和平均子代体质量、CD3^(+)T、CD4^(+)T、CD4^(+)/CD8^(+)T细胞比例降低(P<0.05)。结论:Gal可能通过抑制IL-6/STAT3通路抑制炎症反应、调节细胞免疫,从而发挥缓解PE症状、改善妊娠结局的作用。Objective:To investigate the impacts of galangin(Gal)on the immune inflammatory response in preeclampsia(PE)rats by regulating the IL-6/signal transducer and activator of transcription 3(STAT3)signaling pathway.Methods:Pregnant rats were injected subcutaneously with L-arginine methyl ester(L-NAME 125 mg/kg)to establish a PE model.After successful modeling,they were randomly grouped into Model group,low,medium and high doses Gal groups(10,30,and 60 mg/kg)and activator group(60 mg/kg Gal^(+)0.05 mg/kg IL-6/STAT3 pathway activator rIL-6).Twelve pregnant rats of the same period were randomly selected as the control group,and each group was given corresponding drugs by gavage and intraperitoneal injection,once a day for a continuous week.The levels of mean caudal artery pressure(MAP)and 24-hour urinary protein and blood urea nitrogen(BUN)in rats during the third trimester of pregnancy were measured using a blood pressure tester and a fully automated biochemical analyzer;the number and weight of the average offspring of pregnant mice in each group were calculated,and the pregnancy outcome was analyzed;HE staining was applied to observe the pathological damage of rat placenta;ELISA was applied to detect the levels of IL-6,IL-1βand TNF-αin the placenta of rats in each group;the proportion of T lymphocytes in rat peripheral blood was detected by flow cytometry;Western blot was applied to detect the expression of IL-6/STAT3 pathway protein in rat placenta.Results:Compared with control group,the levels of MAP,24-hour urinary protein,BUN,IL-6,IL-1β,TNF-α,the CD8^(+)T cells,and the expression levels of IL-6 and p-STAT3/STAT3 proteins in Model group were obviously increased,the placenta tissue was severely damaged,the mean offspring number and mean offspring weight,the proportions of CD3^(+)T,CD4^(+)T,and CD4^(+)/CD8^(+)T cells were decreased(P<0.05);compared with Model group,the levels of MAP,24-hour urinary protein,BUN,IL-6,IL-1β,TNF-α,the CD8^(+)T cells,and the expression levels of IL-6 and p-STAT3/STAT3 proteins in G

关 键 词：高良姜素 IL-6/STAT3信号通路 子痫前期 免疫炎症反应 

分 类 号：R714.24[医药卫生—妇产科学]