SIF干预肥胖大鼠下丘脑瘦素介导JAK/STAT信号通路的研究  

Study of leptin-dependent signaling JAK / STAT in hypothalamus after treated by SIF on obese rats

作　　者：陈晓林[1] 罗启慧[1,2] 唐秀莹[1] 刘芸[1] 李立科[1] 陈正礼[1,2] 

机构地区：[1]四川农业大学动物医学院,四川成都611130 [2]四川农业大学实验动物工程技术中心,四川雅安625014

出　　处：《浙江农业学报》2016年第3期420-427,共8页Acta Agriculturae Zhejiangensis

基　　金：国家科技支撑计划项目(2014BAI03B01);国家重大科学仪器设备开发专项(2013YQ49085906);四川省青年科技创新研究团队项目(2013TD0015)

摘　　要：通过观察SIF对肥胖大鼠下丘脑中瘦素介导的信号通路蛋白表达的影响,探讨SIF对肥胖大鼠的干预机制。采用高脂饲料饲喂大鼠,建立肥胖动物模型,并将肥胖大鼠分为4组,分别灌胃SIF,剂量为:对照组(Ⅰ组)0 mg·kg^(–1)、低剂量组(Ⅱ组)50 mg·kg^(–1)、中剂量组(Ⅲ组)150 mg·kg^(–1)、高剂量组(Ⅳ组)450 mg·kg^(–1),并设置正常大鼠基础组(Ⅴ组),饲喂基础饲料,并灌胃给予SIF处理等体积的羧甲基纤维素钠,连续4周。采用HE染色法观察下丘脑组织学结构变化,免疫组织化学SABC法检测下丘脑中瘦素介导的JAK/STAT信号转导通路蛋白OB-Rb(瘦素受体长型),JAK2(内源性酪氨酸蛋白激酶2),p-STAT3(磷酸化的信号转导与转录激活子3),SOCS3(细胞因子信号3抑制因子),NPY(神经肽Y)的表达水平。结果显示:高剂量组和基础组OB-Rb,JAK2,p-STAT3的阳性表达水平显著高于其他组(P<0.05),且前述蛋白均有随SIF的剂量增加而表达增多趋势。高剂量组和基础组的SOCS3和NPY表达水平显著较其他组低(P<0.05),但NPY在背内侧核和室旁核的表达随SIF的剂量增加而增多。OB-Rb,JAK2,p-STAT3,SOCS3和NPY均在下丘脑广泛表达,并随SIF的剂量增加而变化,提示SIF对瘦素介导的信号通路有一定作用并与机体能量的调节密切相关;SIF通过干预大鼠下丘脑瘦素JAK/STAT信号通路具有减重作用,并呈剂量依赖性。Soy isoflavone（ SIF） had effect on decreasing blood lipids. The present research focused on whether it could lose body weight by regulating leptin level. The experiment was designed to investigate the effects of SIF on leptin-dependent signaling in hypothalamus of obese rats. Food-induced obese rats model was established by feeding with high oil diet,then the obese rats were randomly divided into four groups（ GroupⅠ-Ⅳ） fed with SIF 0（ control group）,50（ low dose group）,150（ medium dose group） and 450（ high dose group） mg·kg^（–1）body weight,respectively. In addition,the control group（ Group V,basis group） rats were fed with low oil basal diet. The experi-ment lasted for 4 weeks. At the end of the experiment,all experimental rats were euthanized with pentobarbital sodium and sections of their hypothalamus were prepared and stained with HE. The expressions and positive rates of the main proteins of leptin-JAK / STAT signaling,i. e. OB-Rb,JAK2,p-STAT3,SOCS3,NPY were detected by immunohistochemical SABC,respectively. The results showed that the expressions and positive rates of OB-Rb,JAK2,pSTAT3 in high dose SIF group and basis group were both significantly higher than those in other groups（ P〈0. 05）,and their expression levels were raising with the increased dose of SIF. On the contrary,the levels and positive rates of SOCS3 and NPY in high and basis group were the least compared with other groups,and the difference was significant（ P〈0. 05）,but the expression of NPY was rising in dorsomedial nucleus and paraventricular nucleus following the increased dose of SIF. Above all,SIF had affect on leptin-dependent signaling road. In conclusion,the five proteins were closely related to body energy regulation. SIF could lose body weight by interfering the leptin-JAK / STAT signaling of hypothalamus in obese rat in a dose dependent manner.

关 键 词：大豆异黄酮 免疫组织化学SABC法 OB-Rb JAK2 P-STAT3 SOCS3 NPY 

分 类 号：S816.75[农业科学—饲料科学]