左归降糖解郁方对糖尿病并发抑郁症大鼠前额叶皮层IR/IRS-1信号通路和能量代谢的影响  

Effects of Zuogui Jiangtang Jieyu Decoction on IR/IRS-1 Signaling Pathway and Energy Metabolism in Prefrontal Cortex of Rats with Diabetes Complicated with Depression

作　　者：杨蕙[1,2] 朱青 李薇[1] 雷诗卉 刘检[1,2] 孟盼[2] 刘林[1] 肖望重[1] 王宇红[2] YANG Hui;ZHU Qing;LI Wei;LEI Shihui;LIU Jian;MENG Pan;LIU Lin;XIAO Wangzhong;WANG Yuhong(Medical Innovation Experimental Center,The First Hospital of Hunan University of Chinese Medicine,Changsha 410007,China;Technology Innovation Center,Hunan University of Chinese Medicine,Changsha 410208,China;Hunan Cancer Hospital,The Affiliated Cancer Hospital of Xiangya School of Medicine,Central South University,Changsha 410013,China)

机构地区：[1]湖南中医药大学第一附属医院医学创新实验中心,湖南长沙410007 [2]湖南中医药大学科技创新中心,湖南长沙410208 [3]湖南省肿瘤医院,中南大学湘雅医学院附属肿瘤医院,湖南长沙410013

出　　处：《中国中医药信息杂志》2022年第2期74-78,共5页Chinese Journal of Information on Traditional Chinese Medicine

基　　金：国家自然科学基金(81874464);湖南省自然科学基金(2019JJ80021);湖南省卫生健康委科研计划项目(202102041447);湖南中医药大学研究生创新课题(2020CX04)。

摘　　要：目的观察左归降糖解郁方对糖尿病并发抑郁症大鼠前额叶皮层胰岛素信号通路相关蛋白表达及能量代谢的影响。方法建立糖尿病并发抑郁症大鼠模型。将大鼠随机分为对照组、模型组、阳性药(二甲双胍+氟西汀)组和左归降糖解郁方高、中、低剂量组,各组灌胃给予相应药物4周后,尾尖采血测量大鼠空腹血糖,旷场实验和强迫游泳实验评价大鼠抑郁样行为,ELISA检测大鼠血清胆固醇(TC)、三酰甘油(TG)及前额叶皮层葡萄糖和丙酮酸含量,Western blot检测大鼠前额叶皮层胰岛素受体(IR)、胰岛素受体底物-1(IRS-1)、p-IR、p-IRS-1蛋白表达及葡萄糖转运体4(GLUT4)蛋白的膜表达。结果与对照组比较,模型组大鼠空腹血糖、血清TC和TG含量显著增加(P<0.01,P<0.05),旷场实验活动次数显著减少,强迫游泳实验不动时间显著延长(P<0.01),大鼠前额叶皮层葡萄糖含量显著增加,丙酮酸含量显著减少,p-IR/IR和p-IRS-1/IRS-1比值及GLUT4蛋白膜表达均显著降低(P<0.01,P<0.05);与模型组比较,左归降糖解郁方高剂量组大鼠空腹血糖、血清TC和TG含量减少(P<0.01),旷场实验活动次数增加,强迫游泳实验不动时间缩短(P<0.01),大鼠前额叶皮层葡萄糖含量显著减少,丙酮酸含量显著增加,p-IR/IR和p-IRS-1/IRS-1比值及GLUT4蛋白膜表达均显著升高(P<0.01)。结论左归降糖解郁方可通过激活糖尿病并发抑郁症大鼠前额叶皮层IR/IRS-1信号通路,促进GLUT4膜转位并加速神经元能量代谢,从而发挥抗抑郁作用。Objective To observe the effect of Zuogui Jiangtang Jieyu Decoction on the energy metabolism and insulin signaling pathway related protein expression in the prefrontal cortex of rats with diabetes complicated with depression.Methods Rats model of diabetes complicated with depression was established.Rats were randomly divided into control group,model group,positive drug group(metformin combined with fluoxetine),Zuogui Jiangtang Jieyu Decoction high-,medium,and low-dosage groups.After 4 weeks of administration of corresponding drug for gavage,blood was collected from the tail tip to measure the fasting blood glucose of the rats.The open field test and forced swimming test were used to evaluate the depression-like behavior of rats.ELISA was used to detect the total contents of cholesterol(TC)and triglyceride(TG)in serum and the content of glucose and pyruvate in the prefrontal cortex.Western blot was used to detect the proteins expression of insulin receptor(IR),insulin receptor substrate(IRS-1),p-IR and p-IRS-1 in the prefrontal cortex and the membrane expression of glucose transporter 4(GLUT4).Results Compared with the control group,the contents of fasting blood glucose,TC and TG in serum significantly increased in the model group(P<0.01,P<0.05).The immobility time was significantly prolonged in forced swimming test and the number of activities was significantly reduced in the open field experiment(P<0.01).The content of glucose in the prefrontal cortex significantly increased,the content of pyruvate significantly decreased,and the ratio of p-IR/IR,p-IRS-1/IRS-1 and the membrane expression of GLUT4 significantly decreased(P<0.01,P<0.05).Compared with the model group,the contents of fasting blood glucose,TC and TG in serum significantly reduced in Zuogui Jiangtang Jieyu Decoction high-dosage group.The immobility time was significantly shortened in the forced swimming test and the number of activities was significantly increased in the open field test(P<0.01).The content of glucose in the prefrontal cortex significa

关 键 词：左归降糖解郁方 糖尿病并发抑郁症 前额叶皮层 胰岛素受体 能量代谢 大鼠 

分 类 号：R285.5[医药卫生—中药学]