首页|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

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

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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-1d-1杜鹃素)、高剂量实验组(高盐饲料+灌胃50 mg·kg-1d-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(CaCl2)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,均显著降低,差异均有统计学意义(P<0.05,P<0.01).结论 杜鹃素可能通过下调JAK2/STAT3通路改善高盐致小鼠脑基底动脉炎症和肌张力异常.
Farrerol improves the inflammation and abnormal muscle tone of cerebral basilar artery in mice induced by high salt via down-regulating JAK2/STAT3 pathway
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 50 mg·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)-1β were(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±0.04;the protein expression levels of STAT3 were 0.58±0.07,1.93±0.10,1.62±0.04,1.34±0.06 and 0.88±0.09,respectively.The above indicators in the model group were significantly higher than the normal group(all P<0.01);compared to the model group,the above indicators in the experimental-M and-H groups were significantly reduced(P<0.05,P<0.01).Conclusion Farrerol maybe improve the inflammation and abnormal muscle tone of cerebral basilar artery in mice induced by high salt by downregulating JAK2/STAT3 pathway.

farrerolJanus kinase 2/transcription activator 3high saltcerebral basilar arteryinflammationmuscle tone

侯晓敏、陈亮京、郝雨萱、张明升、秦小江

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山西医科大学基础医学院,山西太原 030001

山西医科大学第二医院全科医学,山西太原 030001

山西医科大学第一医院全科医学,山西太原 030001

山西医科大学公共卫生学院,山西太原 030001

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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

国家自然科学基金青年基金资助项目国家自然科学基金面上资助项目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山西省自然科学基金面上资助项目山西省科技创新人才团队专项基金资助项目山西省科技合作交流专项基金资助项目

8220404282373622NHC202307202103021224227202304051001038202204041101022

2024

中国临床药理学杂志
中国药学会

中国临床药理学杂志

CSTPCD北大核心
影响因子:1.91
ISSN:1001-6821
年,卷(期):2024.40(13)
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