逍遥散对慢性不可预知温和应激大鼠下丘脑弓状核JAK/STAT通路变化的影响  

Effect of Xiaoyaosan on Changes of JAK/STAT Pathway in Hypothalamic Arcuate Nuclei of Rats With Chronic Mild Unpredictable Stress

作　　者：王一旭 李媛媛[1] 张碧涛 王浩[1,2] 王少贤 WANG Yi-xu;LI Yuan-yuan;ZHANG Bi-tao;WANG Hao;WANG Shao-xian(Hebei University of Chinese Medicine,Shijiazhuang 050200,China;Hebei Key Laboratory of Chinese Medicine Prevention Research on Cardio-cerebrovascular Diseases,Shijiazhuang 050091,China)

机构地区：[1]河北中医学院,石家庄050200 [2]河北省心脑血管病中医药防治研究重点实验室,石家庄050091

出　　处：《中国实验方剂学杂志》2020年第21期21-27,共7页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(81673881,81202644);河北省自然科学基金项目(H2016423049);河北省高层次人才项目(A201901038);河北中医学院2019年研究生创新立项项目(XCXZZSS2019004);河北中医学院优秀学生科研能力提升项目(YXZ2019011)。

摘　　要：目的:观测慢性不可预知温和应激(CUMS)模型大鼠下丘脑弓状核(ARC)中瘦素受体(ob-R)-酪氨酸激酶Janus2(JAK2)/转录激活因子3(STAT3)通路变化及逍遥散的调节作用。方法:60只SD雄性大鼠随机分为正常组、模型组、逍遥散组、氟西汀组。适应性喂养1周,模型组、逍遥散组、氟西汀组大鼠通过不可预知温和刺激方式复制慢性心理应激大鼠模型,同时灌服相应药物,逍遥散19.27 g·kg-1·d-1,氟西汀2 mg·kg-1·d-1(按成人平均体质量60 kg用药量换算),正常组和模型组大鼠灌服同体积生理盐水,实验6周。观察各组大鼠体质量、摄食量、糖水消耗率、行为学变化;实时荧光定量聚合酶链式反应(Realtime PCR)和蛋白免疫印迹法(Western blot)检测大鼠下丘脑弓状核ob-R,JAK2,STAT3 mRNA和蛋白表达。结果:与正常组比较,模型组大鼠体质量、摄食量明显下降(P<0.05,P<0.01),糖水消耗、旷场实验行为学总路程和中央区总路程均有明显减少,下丘脑弓状核ob-R,JAK2,STAT3蛋白及mRNA表达升高明显(P<0.05,P<0.01);与模型组比较,逍遥散组大鼠体质量于实验第7,14,21,28天明显升高(P<0.05,P<0.01),大鼠摄食量于实验第21,35天明显升高(P<0.05),糖水消耗、旷场实验行为学总路程和中央区总路程均明显改善;逍遥散对模型大鼠下丘脑弓状核ob-R,JAK2,STAT3蛋白及mRNA表达有相应的调节作用(P<0.05,P<0.01)。结论:逍遥散调节慢性不可预知温和应激大鼠体质量、食欲和能量代谢作用,可能与下丘脑弓状核ob-RJAK2/STAT3通路相关。Objective:To observe the changes of leptin receptor-tyrosine kinase Janus2(JAK2)/signal transducer and activator of transcription 3(STAT3)pathway and the regulatory effect of Xiaoyaosan on the hypothalamic arcuate nuclei of rats with chronic mild unpredictable stress model(CUMS). Method: Sixty male sprague-dawley rats were randomly divided into normal group,model group,Xiaoyaosan group,and fluoxetine group. After one-week adaptive feeding,the rats in model group,Xiaoyaosan group and fluoxetine group were uesd to replicate the chronic psychological stress rat model through mild unpredictable stimulation. Meanwhile,they were simultaneously administered the corresponding drugs, Xiaoyaosan 19.27 g·kg-1·d-1, Fluoxetine2 mg·kg-1·d-1(based on the average adult body weight of 60 kg),the rats in the normal group and the model group were given the same volume of normal saline for 6 weeks. The body weight,food intake,sucrose consumption ratios,and the experimental behavior in the open field test(OFT)of the groups were observed.Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR)and Western blot were used to detect the expressions of ob-R, JAK2, and STAT3 in the arcuate nucleus of rat hypothalamus. Result:Compared with the normal group,the body weight and food intake of the model group were significantly decreased(P<0.05,P<0.01),the sucrose consumption ratios,the total behavioral distance of the experimental field and the total distance of the central area were significantly reduced,the protein and mRNA expressions of ob-R,JAK2,STAT3 in the arcuate nucleus of hypothalamus in rats increased significantly(P<0.05,P<0.01).Compared with the model group,the body weight of Xiaoyaosan group increased significantly on the 7 th,14 th,21 stand 28 thdays(P<0.05,P<0.01),the food intake of rats increased significantly on the 21 stand 35 thdays of the experiment(P<0.05),and the sucrose consumption ratios,the total distance of the experimental behavior in the open field test(OFT)and the total distance of the cent

关 键 词：慢性不可预知温和应激 弓状核 瘦素受体 酪氨酸激酶Janus2/转录激活因子3 逍遥散 

分 类 号：R2-0[医药卫生—中医学] R22