杜鹃素下调JAK2/STAT3通路改善高盐致脑基底动脉炎症和肌张力异常的研究  

Farrerol improves the inflammation and abnormal muscle tone of cerebral basilar artery in mice induced by high salt via down-regulating JAK2/STAT3 pathway

作　　者：侯晓敏[1] 陈亮京 郝雨萱 张明升[1] 秦小江[2] HOU Xiao-min;CHEN Liang-jing;HAO Yu-xuan;ZHANG Ming-sheng;QIN Xiao-jiang(School of Basic Medicine,Shanxi Medical University,Taiyuan 030001,Shanxi Province,China;School of Public Health,Shanxi Medical University,Taiyuan 030001,Shanxi Province,China;General Medicine,Second Hospital of Shanxi Medical University,Taiyuan 030001,Shanxi Province,China;General Medicine,First Hospital of Shanxi Medical University,Taiyuan 030001,Shanxi Province,China)

机构地区：[1]山西医科大学基础医学院,山西太原030001 [2]山西医科大学公共卫生学院,山西太原030001 [3]山西医科大学第二医院全科医学,山西太原030001 [4]山西医科大学第一医院全科医学,山西太原030001

出　　处：《中国临床药理学杂志》2024年第13期1898-1902,共5页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金青年基金资助项目(82204042);国家自然科学基金面上资助项目(82373622);国家卫生健康委员会尘肺病重点实验室开放课题资助项目(NHC202307);山西省自然科学基金面上资助项目(202103021224227);山西省科技创新人才团队专项基金资助项目(202304051001038);山西省科技合作交流专项基金资助项目(202204041101022)。

摘　　要：目的基于Janus激酶2(JAK2)/转录激活子3(STAT3)通路探讨杜鹃素对高盐诱导的小鼠脑基底动脉炎症和肌张力异常的抑制作用及其分子机制。方法用喂养高盐饲料的方法建立高盐模型。将50只C57BL/6J小鼠随机分成正常组(正常饲养)、模型组(高盐饲料)、低剂量实验组(高盐饲料+灌胃12.5 mg·kg^(-1)·d^(-1)杜鹃素)、中剂量实验组(高盐饲料+灌胃25 mg·kg^(-1)d^(-1)杜鹃素)、高剂量实验组(高盐饲料+灌胃50 mg·kg^(-1)d^(-1)杜鹃素),每组10只,干预12周。用微血管张力测定仪检测小鼠脑基底动脉对血管收缩剂的收缩反应;用酶联免疫吸附试验(ELISA)法检测炎性细胞因子水平;用蛋白质印迹法检测基底动脉组织JAK2/STAT3通路的相关蛋白表达。结果正常组、模型组和低、中、高剂量实验组脑基底动脉对60 mmol·L^(-1)氯化钾(KCl)的收缩幅度分别为(2.19±0.13)、(2.66±0.11)、(2.52±0.09)、(2.41±0.08)和(2.25±0.10)mN;对10^(-5)mol·L^(-1)血管加压素(AVP)的收缩幅度分别为(1.98±0.09)、(2.46±0.08)、(2.33±0.12)、(2.11±0.10)和(2.05±0.06)mN;对2.5 mmol·L^(-1)氯化钙(CaCl_(2))的收缩幅度分别为(1.77±0.08)、(2.09±0.09)、(2.03±0.08)、(1.94±0.05)和(1.86±0.06)mN;血清中白细胞介素(IL)-1β水平分别为(10.10±3.21)、(47.28±4.78)、(40.16±3.98)、(35.87±4.12)和(20.32±3.17)pg·mL^(-1);肿瘤坏死因子-α(TNF-α)水平分别为(60.26±5.43)、(134.32±4.15)、(110.65±3.56)、(90.79±5.25)和(81.54±6.23)pg·mL^(-1);趋化因子配体3(CCL3)水平分别为(68.93±4.16)、(146.37±5.73)、(128.29±4.38)、(100.25±6.82)和(84.16±3.89)pg·mL^(-1);脑基底动脉组织JAK2表达水平分别为0.52±0.05、1.28±0.07、1.11±0.06、0.88±0.09和0.75±0.04;STAT3表达水平分别为0.58±0.07、1.93±0.10、1.62±0.04、1.34±0.06和0.88±0.09。模型组上述指标与正常组比较,均显著增高,差异均有统计学意义(均P<0.01)。中、高剂量实验组上述指标与模型组比较,均显著�Objective To investigate the inhibitory effect of farrerol on inflammation and abnormal muscle tone of cerebral basilar artery in mice induced by high salt and its molecular mechanism based on the Janus kinase 2(JAK2)/Transcription activator 3(STAT3)pathway.Methods A total of fifty C57BL/6J mice were randomly divided into normal group(normal feeding),model group(high salt diet),experimental-L group(high salt diet+oral administration of 12.5 mg·kg^(-1)·d^(-1)farrerol),experimental-M group(high salt diet+oral administration of 25 mg·kg^(-1)·d^(-1)farrerol)and experimental-H group(high salt diet+oral administration of 50mg·kg^(-1)·d^(-1)farrerol).The model was prepared for 12 weeks.The contractile response of the cerebral basilar artery of mice in each group to vasoconstrictor was recorded with myographs.Enzyme linked immunosorbent assay(ELISA)were used to detect the levels of inflammatory factor.The protein expression levels of JAK2/STAT3 pathway related proteins were detected by Western blot.Results In the normal group,model group,experimental-L group,experimental-M group,experimental-H group,the contraction effects of the cerebral basilar artery to 60 mmol·L^(-1)potassium chloride(KCl)were(2.19±0.13),(2.66±0.11),(2.52±0.09),(2.41±0.08)and(2.25±0.10)mN;the contraction effects to 10^(-5)mol·L^(-1)vasopressiu(AVP)were(1.98±0.09),(2.46±0.08),(2.33±0.12),(2.11±0.10)and(2.05±0.06)mN;the contraction effects to 2.5 mmol·L^(-1)calcium chloride(CaCl2)were(1.77±0.08),(2.09±0.09),(2.03±0.08),(1.94±0.05)and(1.86±0.06)mN;in the serum,the levels of interleukin(IL)-1βwere(10.10±3.21),(47.28±4.78),(40.16±3.98),(35.87±4.12)and(20.32±3.17)pg·mL^(-1);the levels of tumor necrosis factor-α(TNF-α)were(60.26±5.43),(134.32±4.15),(110.65±3.56),(90.79±5.25)and(81.54±6.23)pg·mL^(-1);the levels of chemokine ligand 3(CCL3)were(68.93±4.16),(146.37±5.73),(128.29±4.38),(100.25±6.82)and(84.16±3.89)pg·mL^(-1);the protein expression levels of JAK2 were 0.52±0.05,1.28±0.07,1.11±0.06,0.88±0.09 and 0.75

关 键 词：杜鹃素 Janus激酶2/转录激活子3 高盐 脑基底动脉 炎症 肌张力 

分 类 号：R28[医药卫生—中药学]