芒柄花素调节JAK2/STAT3信号通路对妊娠高血压大鼠的治疗作用  

Therapeutic Effects of Formononetin Regulating JAK2/STAT3 Signaling Pathway on Rats with Pregnancy-induced Hypertension

作　　者：刘洋 赵巧棉 杨颖 李丽英 栾燕东 LIU Yang;ZHAO Qiaoman;YANG Ying;LI Liying;LUAN Yandong(Chengde Maternal and Child Health Care Hospital,Chengde 067000,Hebei,China;不详)

机构地区：[1]承德市妇幼保健院,河北承德067000 [2]承德市荣复军人医院

出　　处：《中西医结合心脑血管病杂志》2024年第5期823-828,共6页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：河北省承德市科学技术研究与发展计划项目(No.202109A011)。

摘　　要：目的:探讨芒柄花素(FMN)对妊娠高血压(PIH)大鼠的治疗作用及可能机制。方法:将妊娠大鼠分为正常组(Normal组,生理盐水)、PIH组(生理盐水)、FMN组[40 mg/(kg·d)FMN]、Janus激酶2(JAK2)抑制剂组[AG490组,5 mg/(kg·d)AG490]、FMN+JAK2抑制剂组[FMN+AG490组,40 mg/(kg·d)FMN+5 mg/(kg·d)AG490],每组12只。除Normal组外,其余各组大鼠连续4 d皮下注射125 mg/(kg·d)L-精氨酸甲酯构建PIH模型。观察大鼠尾静脉压、24 h尿蛋白含量,血清血管内皮因子[内皮素1(ET-1)、一氧化氮(NO)]、炎性因子[肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)]、心肌损伤指标[肌酸激酶同工酶MB(CK-MB)、心肌肌钙蛋白I(cTnI)]、肾损伤指标[血尿素氮(BUN)、血肌酐(SCr)]水平,心肌、肾组织病理学变化及心肌、肾组织中氧化应激指标[丙二醛(MDA)和总超氧化物歧化酶(T-SOD)]和JAK2/信号转导和转录激活因子3(STAT3)信号通路相关蛋白(JAK2、p-JAK2、STAT3、p-STAT3)表达。结果:给药结束后,与Normal组比较,PIH组大鼠尾静脉压、24 h尿蛋白含量升高,血清ET-1、TNF-α、IL-6、CK-MB、cTnI、BUN、SCr水平及心肌、肾组织中MDA含量和p-JAK2/JAK2、p-STAT3/STAT3比值升高(P<0.05),血清NO水平和心肌、肾组织中T-SOD活性降低(P<0.05),且心肌、肾组织存在明显的病理损伤。与PIH组比较,FMN组、AG490组和FMN+AG490组大鼠尾静脉压、24 h尿蛋白含量降低,血清ET-1、TNF-α、IL-6、CK-MB、cTnI、BUN、SCr水平及心肌、肾组织中MDA含量和p-JAK2/JAK2、p-STAT3/STAT3比值降低(P<0.05),血清NO水平和心肌、肾组织中T-SOD活性升高(P<0.05),且心肌、肾组织病理损伤均有所改善;其中FMN+AG490组上述指标变化均显著优于FMN组、AG490组。结论:FMN可能通过抑制JAK2/STAT3信号通路,减轻心肌、肾组织中氧化应激和全身炎症反应,改善血管内皮舒缩功能,降低血压,减轻PIH大鼠心肌、肾组织损伤。Objective:To investigate the therapeutic effect of formononetin(FMN)on rats with pregnancy-induced hypertension(PIH)and its possible mechanism.Methods:Pregnant rats were divided into Normal group(normal saline),PIH group(normal saline),FMN group[40 mg/(kg·d)FMN],Janus kinase 2(JAK2)inhibitor group[AG490 group,5 mg/(kg·d)AG490],FMN+JAK2 inhibitor group[FMN+AG490 group,40 mg/(kg·d)FMN+5 mg/(kg·d)AG490],with 12 rats in each group.Except Normal group,the rats in other groups were subcutaneously injected 125 mg/(kg·d)L-arginine methyl ester for 4 consecutive days to establish PIH model.The tail venous pressure of rats and 24 h urinary protein content were observed.Serum vascular endothelial factors[endothelin 1(ET-1),nitric oxide(NO)],inflammatory factors[tumor necrosis factorα(TNF-α),interleukin 6(IL-6)],myocardial injury indexes[creatine kinase isoenzyme MB(CK-MB),myocardial troponin I(cTnI)],kidney injury indexes[blood urea nitrogen(BUN),serum creatinine(SCr)]levels,histopathological changes of myocardium and kidney,and expression of oxidative stress indicators[malondialdehyde(MDA)and total superoxide dismutase(T-SOD)]and JAK2/signal transduction and transcriptional activator 3(STAT3)signaling pathway-related proteins(JAK2,p-JAK2,STAT3,p-STAT3)in myocardium and kidney were detected.Results:After administration,compared with the normal group,tail venous pressure and 24 h urinary protein content in the PIH group,serum ET-1,TNF-α,IL-6,CK-MB,cTnI,BUN,SCr,MDA content and p-JAK2/JAK2 and p-STAT3/STAT3 ratio in myocardial and kidney tissues increased(P<0.05).Serum NO level and T-SOD activity in myocardium and kidney tissues decreased(P<0.05),and there were obvious pathological injuries in myocardium and kidney tissues.Compared with the PIH group,the tail venous pressure,24 h urinary protein content in the FMN group,AG490 group and FMN+AG490 group,Serum ET-1,TNF-α,IL-6,CK-MB,cTnI,BUN,SCr levels,MDA content and p-JAK2/JAK2 and p-STAT3/STAT3 ratios in myocardial and kidney tissues decreased(P<0.05).Serum NO level an

关 键 词：妊娠高血压 芒柄花素 Janus激酶2/信号转导和转录激活因子3信号通路 大鼠 实验研究 

分 类 号：R285.5[医药卫生—中药学]