基于IRS-1/PI3K/Akt通路探讨葛根素对糖尿病大鼠认知功能障碍的保护作用  

Protective Effect of Puerarin on Cognitive Dysfunction in Diabetic Rats Based on IRS-1/PI3K/Akt Pathway

作　　者：郝宏铮[1] 王爱平[2] 王丽[1] 孙海波[2] Hao Hongzheng;Wang Aiping;Wang Li;Sun Haibo(Department of Endocrinology;Department of Otolaryngology,Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110032,China)

机构地区：[1]辽宁中医药大学附属医院内分泌科,沈阳110032 [2]辽宁中医药大学附属医院耳鼻喉科,沈阳110032

出　　处：《中国药师》2019年第7期1220-1226,共7页China Pharmacist

基　　金：第六批全国名老中医药专家学术经验继承项目(编号:2017-432)

摘　　要：目的:基于胰岛素受体底物1/磷脂酰肌醇-3-激酶/蛋白激酶B(IRS-1/PI3K/Akt)通路探讨葛根素对糖尿病大鼠认知功能障碍的保护作用。方法:SD大鼠120只,根据体质量随机分成6组:正常对照组、模型组、阳性对照组(α-硫辛酸,60.0 mg·kg-1)、葛根素低(10.0 mg·kg-1)、中(20.0 mg·kg-1)、高(40.0 mg·kg-1)剂量组,每组20只。构建糖尿病大鼠认知功能障碍模型,并灌胃给予相应药物,正常对照组和模型组给予等体积生理盐水。利用Morris水迷宫试验对大鼠认知功能进行评价;制作HE切片,观察根素对大鼠海马神经元结构的影响;检测大鼠海马组织中IRS-1、PI3K、Akt mRNA水平以及IRS-1、PI3K、Akt、白细胞介素2(IL-2)、白细胞介素6(IL-6)、肿瘤坏死因子-α(TNF-α)蛋白水平。结果:正常对照组海马区神经元细胞完整,结构正常,染色清晰,核呈卵圆形位于中央;模型组海马区可见大量坏死神经元,且细胞脱失现象明显,细胞核固缩;葛根素高剂量组和阳性对照组海马区见少量坏死神经元细胞,且神经元细胞结构较为完整,神经元细胞核呈卵圆形位于中央,分布均匀;葛根素中、低剂量组较模型组而言,坏死神经元细胞减少,但经元疏松紊乱,细胞核固缩,脱失现象明显,具有明显的剂量依赖效应。与正常对照组比较,模型组中期及试验末期血糖水平、逃避潜伏期、IRS-1 mRNA表达水平和IRS-1、IL-2、IL-6、TNF-α蛋白表达水平显著升高(P<0.05),经过原平台位置次数、原平台象限留时间、PI3K、Akt mRNA表达水平和PI3K、Akt蛋白表达水平显著降低(P<0.05)。与模型组比较,葛根素各剂量组及阳性对照组中期及试验末期血糖水平、逃避潜伏期、IRS-1 mRNA表达水平和IRS-1、IL-2、IL-6、TNF-α蛋白表达水平显著降低(P<0.05),经过原平台位置次数、原平台象限留时间、PI3K、Akt mRNA表达水平和PI3K、Akt蛋白表达水平显著升高(P<0.05);各水平的变化与葛根素Objective: To investigate the protective effect of puerarin on cognitive dysfunction in diabetic rats based on IRS-1/PI3 K/Akt pathway. Methods: Totally 120 SD rats were randomly divided into six groups according to the body weight: the control group,the model group,α-lipoic acid group,and puerarin low-,medium-and high-dose groups. All the rats were used to establish diabetic model except for those in the control group,thereafter,the corresponding treatments were given to the rats in each group. At the end of the experiment,HE slices were made and the structure of hippocampal neurons was observed. Morris water maze test was used to evaluate the cognitive function of rats. The mRNA and protein levels of IRS-1,PI3 K and Akt,as well as the levels of IL-2,IL-6 and TNF-α were recorded. Results: In the normal control group,the neurons in hippocampus were intact,the structure was normal,the staining was clear,and the nucleus was oval in the center. In the model group,a large number of necrotic neurons were observed in hippocampus,the cell loss was obvious,and the nucleus was pyknosis;in the puerarin high dose group and the positive control group,a few of necrotic neurons were found inhippocampus,the neuronal cell structure was relatively complete,and the nucleus was oval in the center and evenly distributed. Compared with the model group,the puerarin medium and low dose groups had fewer necrotic neurons,while the cells were loose and disordered,the nucleus was pyknosis,and the phenomenon of loss was obvious with dose-dependent effect. Compared with that in the control group,the escape latency of each puerarin group increased( P < 0.05),the number of times of passing through the original platform position and the time of remaining in the original platform quadrant decreased( P<0.05).Compared with that in the model group,the escape latency in each puerarin group decreased( P<0.05),the number of times passing through the original platform position and the time of remaining in the original platform quadrant increased( P <

关 键 词：胰岛素受体底物1/磷脂酰肌醇-3-激酶/蛋白激酶B 葛根素 糖尿病 认知功能障碍 

分 类 号：R965.1[医药卫生—药理学]