大豆异黄酮对肥胖大鼠肠道瘦素介导 Janus激酶／信号转导及转录激活因子信号转导通路的影响

李立科; 罗启慧; 唐秀莹; 黄超; 陈晓林; 刘文涛; 陈正礼

摘要

This study was conducted to study the regulatory effect of signaling transduction path of leptin⁃de⁃pendent Janus kinase ( JAK )/signal transduction and activator of transcription ( STAT ) in intestine of obese rats treated with soybean isoflavone ( SIF) , and to discuss the intervention mechanism of SIF on obese rats. Eighty SD male rats with the age of 5 weeks were randomly divided into basal diet group ( 12 rats) and high fat diet group ( 68 rats) after adapted to the environment for 1 week, and the rats in basal diet group and high fat diet group were fed with basal diet and high fat diet, respectively. After feeding 8 weeks, the food⁃induced obese rat models were successfully established in high fat diet group. Forty obese rats were selected to divide in⁃to 4 groups which were SIF interfering low, medium and high dose groups and obesity control group, and each group had 10 rats. The rats in low, medium and high dose groups were given 50, 150 and 450 mg/kg BW SIF, respectively, and the rats in basal diet group and obesity control group were given solvent agent through stomach for 5 weeks. During the experiment, the body weight of rats was measured, and the expression and distribution of obese receptor b ( OB⁃Rb) , Janus kinase 2 ( JAK2) , phosphorylated signal transducer and acti⁃vator of transcription 3 ( p⁃STAT3) , suppressor of cytokine signaling 3 ( SOCS3) and neuropeptide Y ( NPY) were detected by immunohistochemical staining of strept avidin⁃biotin complex ( SABC) method. The results showed as follows: the body weight of basal diet group was extremely significantly lower than that of obesity control group at each period ( P<0.01) . After 5 weeks of SIF intervention, the body weight of SIF intervention groups was decreased compared with obesity control group and showed a dose⁃dependence relationship, and the middle and high dose groups were extremely significantly lower than obesity control group ( P<0.01) . OB⁃Rb, JAK2, p⁃STAT3, SOCS3 and NPY of rats of each group all existed in duodenum, jejunum, ileum, colon and rectum. Compared with basal diet group, the expression levels of OB⁃Rb, JAK2, p⁃STAT3, SOCS3 and NPY at different intestine segments of rats of obesity control group were significantly decreased (P<0.05). Com⁃pared with obesity control group, the expression levels of OB⁃Rb, JAK2, p⁃STAT3 and NPY at different in⁃testine segments of rats of SIF intervention groups were obviously increased, and overall showed a dose⁃de⁃pendence relationship. The results suggest that SIF can increase the expression of intestinal OB⁃Rb, activate JAK, accelerate STAT phosphorylation, improve energy metabolism, attenuate leptin resistance, and then play a role on weight loss of obese rats.%本试验旨在研究大豆异黄酮（ SIF）对肥胖大鼠肠道瘦素介导Janus激酶（ JAK）／信号转导及转录激活因子（ STAT）信号转导通路的调控作用，探讨SIF对肥胖大鼠的干预机制。选取80只5周龄SD 雄性大鼠，适应环境1周后，随机分为基础饲粮组（12只）和高脂饲粮组（68只），分别饲喂基础饲粮和高脂饲粮，饲喂8周后高脂饲粮组大鼠成功建立食源型肥胖大鼠模型。将40只肥胖大鼠随机分为SIF干预低、中、高剂量组和肥胖对照组，每组10只。低、中、高剂量组大鼠分别灌胃50、150、450 mg／kg BW的SIF提取物，基础饲粮组和肥胖对照组灌胃不含SIF提取物的溶媒剂。 SIF连续干预肥胖大鼠5周，监测大鼠体重，并采用免疫组织化学链霉亲和素－生物素复合物（ SABC ）染色法研究大鼠肠道中长型瘦素受体（ OB⁃Rb ）、Janus 激酶2（ JAK2）、磷酸化的信号转导与转录激活因子3（ p⁃STAT3）、细胞因子信号3抑制因子（ SOCS3）和神经肽Y（ NPY）的分布和表达。结果显示：试验各时期基础饲粮组大鼠体重均极显著低于肥胖对照组（ P＜0．01）。 SIF干预5周后，与肥胖对照组相比，各SIF干预组大鼠体重均下降，并表现出剂量依赖性，其中中、高剂量组极显著低于肥胖对照组（ P＜0．01）。各组大鼠OB⁃Rb、JAK2、p⁃STAT3、SOCS3和NPY在十二指肠、空肠、回肠、结肠和直肠均有表达；同基础饲粮组相比，肥胖对照组大鼠上述5种因子在各肠段的表达量均显著降低（P＜0．05）；SIF 干预组中 OB⁃Rb、JAK2、p⁃STAT3和NPY的表达量在各肠段均较肥胖对照组增多，总体呈现剂量依赖性。由此得出，SIF可通过增加肠道中OB⁃Rb的表达，激活JAK，加速STAT的磷酸化，改善能量代谢，减弱肥胖大鼠瘦素抵抗状态，来起到减重作用。

大豆异黄酮对肥胖大鼠肠道瘦素介导 Janus激酶／信号转导及转录激活因子信号转导通路的影响

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