基于JAK2/STAT3信号通路探讨益脉颗粒调控白色脂肪棕色化干预高脂小鼠学习记忆障碍作用机制  

Exploration on the mechanism of Yimai Granules regulating white fat browning in the intervention of learning and memory impairment in high-fat mice based on JAK2/STAT3 signaling pathway

作　　者：谢思梦 刘勇明[1] 程美佳 鞠业涛 王鑫淼 袁常斌 杨关林[3] 闵冬雨[1] XIE Simeng;LIU Yongming;CHENG Meijia;JU Yetao;WANG Xinmiao;YUAN Changbin;YANG Guanlin;MIN Dongyu(Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110032,China;Shanghai Pessenuo Biotechnology Co.,LTD.,Shanghai 200030,China;Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China)

机构地区：[1]辽宁中医药大学附属医院,沈阳110032 [2]上海派森诺生物科技股份有限公司,上海200030 [3]辽宁中医药大学,沈阳110847

出　　处：《中华中医药杂志》2024年第7期3416-3423,共8页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.82174114);沈阳市科技局公共卫生研发医工结合项目(No.22-321-32-14);辽宁中医药大学中医脏象理论及应用教育部重点实验室开放基金项目(No.zyzx2006);辽宁中医药大学附属医院育苗基金项目(No.YM202025,No.YM202132)。

摘　　要：目的:探讨益脉颗粒通过JAK激酶2(JAK2)/信号转导及转录激活蛋白3(STAT3)信号通路调控白色脂肪棕色化干预高脂小鼠学习记忆障碍的作用机制。方法:将40只C57BL/6J小鼠按照随机数表法分为对照组、模型组、益脉颗粒组和辛伐他汀组,每组10只,对照组以普通饲料喂养,模型组、益脉颗粒组和辛伐他汀组以高脂饲料持续喂养44周建立高脂学习记忆障碍模型,益脉颗粒组(7.2g/kg)与辛伐他汀组(1.76mg/kg)于第14周分别以相应药物进行灌胃,对照组与模型组以等体积0.9%氯化钠溶液进行灌胃,每日2次,持续给药30周。44周后采用Morris水迷宫和空间探索实验对小鼠学习记忆能力进行检测,HE染色观察海马CA1区形态及附睾附近白色脂肪组织形态,ELISA检测小鼠血清总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)水平及白色脂肪匀浆上清液瘦素(LP)含量,WesternBlot检测UCP-1、PRDM16、P-JAK2、JAK2、P-STAT3、STAT3蛋白表达水平。结果:与对照组比较,模型组小鼠逃避潜伏期及空间定向穿梭能力下降(P<0.01),海马CA1区神经元排列不均匀且出现液化坏死及胞核固缩,血清TC、TG、LDL-C水平显著升高(P<0.01),HDL-C水平显著显著降低(P<0.01),脂肪组织呈大分子空泡状,脂肪匀浆上清液中LP水平显著降低(P<0.01),脂肪组织PRDM16、UCP-1及p-JAK2/JAK2、P-STAT3/STAT3蛋白相对表达水平显著降低(P<0.01)。与模型组比较,益脉颗粒组和辛伐他汀组小鼠定向航行及学习记忆能力得到了显著改善(P<0.01),血清TC、TG、LDL-C水平显著降低(P<0.01),HDL-C水平显著升高(P<0.01,P<0.05),海马CA1区神经元逐渐完整,胞核分布均匀,脂肪组织出现多腔脂滴结构并出现棕色化趋势,脂肪匀浆中LP水平显著升高(P<0.01),脂肪组织PRDM16、UCP-1及p-JAK2/JAK2、p-STAT3/STAT3蛋白表达水平显著升高(P<0.01,P<0.05)。结论:益脉颗粒能够降低高脂学习记忆�Objective:To explore the mechanism of Yimai Granules in regulating white adipose browning and intervening in learning and memory disorders in high-fat mice through the JAK kinase 2(JAK2)/signal transduction and transcriptional activation protein 3(STAT3)signaling pathway.Methods:Forty C57BL/6J mice were randomly divided into control group,model group,Yimai Granules group,and Simvastatin group using a random number table method,with 10 mice in each group.The control group was fed with regular feed,while the model group,Yimai Granules group,and Simvastatin group were continuously fed with high-fat feed for 44 weeks to establish a high-fat learning and memory impairment model.The Yimai Granules group(7.2 g/kg)and Simvastatin group(1.76 mg/kg)were gavaged with corresponding drugs at week 14,while the control group and model group were gavaged with an equal volume of 0.9%sodium chloride solution twice a day for 30 weeks.After 44 weeks,the learning and memory abilities of mice were tested using Morris water maze and spatial exploration experiments.HE staining was used to observe the morphology of the hippocampal CA1 region and the white adipose tissue near the epididymis.ELISA was used to detect the levels of total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),and the content of leptin(LP)in the supernatant of the white adipose tissue homogenate.The expression levels of UCP-1,PRDM16,p-JAK2,JAK2,p-STAT3,and STAT3 proteins in mice were detected.Results:Compared with the control group,the model group mice showed a decrease in escape latency and spatial directional shuttle ability(P<0.01),uneven arrangement of neurons in the CAl area of the hippocampus,liquefaction necrosis and nuclear pyknosis,significant increase in serum TC,TG,LDL-C levels(P<0.01),and significant decrease in HDL-C levels(P<0.01).The adipose tissue appeared as large molecule vacuoles,and the LP level in the supernatant of the adipose homogenate was significantly reduced(P<0.01).Th

关 键 词：轻度认知障碍 益脉颗粒 白色脂肪组织 棕色脂肪组织 JAK激酶2/信号转导及转录激活蛋白3信号通路 机制 动物模型 血脂 

分 类 号：R285.5[医药卫生—中药学]