摘要
目的基于PERK/Nrf2通路探讨复方芪鹰颗粒对糖尿病周围神经病变(DPN)大鼠的作用机制。方法将72只体重180~220 g、8周龄的SPF级雄性Wistar大鼠采用随机数字表法分为正常对照组、模型组、阳性药组及复方芪鹰颗粒低、中、高剂量组,每组12只。除正常对照组外,其余五组均持续喂食高脂饲料,8周后注射链脲佐菌素(30 mg/kg),然后选取空腹血糖>11.1 mol/L的大鼠继续高脂饮食4周构建DPN模型。DPN造模成功后,复方芪鹰颗粒低、中、高剂量组分别给予复方芪鹰颗粒1.17、2.34、4.68 g/kg,阳性药组给予氧化三甲胺(110 mg/kg),灌胃2 ml/次,1次/d,正常对照组、模型组给予等量双蒸水。干预4周,比较六组干预前后的血糖变化,对六组坐骨神经进行苏木精-伊红染色,采用蛋白质印迹法检测六组坐骨神经中葡萄糖调节蛋白78(GRP78)、蛋白激酶RNA样内质网激酶(PERK)、磷酸化PERK(p-PERK)、转录激活因子4(ATF4)、核转录因子红系2相关因子2(Nrf2)、C/EBP同源蛋白(CHOP)、胱天蛋白酶-3(caspase-3)表达水平。结果正常对照组有髓神经纤维结构完整、分布均匀、排列规则,轴索、髓鞘及神经膜形态结构良好、完整,神经内膜形态结构正常;模型组有髓神经纤维脱失、减少,部分排列紊乱,部分轴索变性,节段性脱髓鞘,神经膜增厚,神经内膜胶原纤维增生;复方芪鹰颗粒低、中、高剂量组髓神经纤维轴索变性、脱髓鞘、神经膜增厚及神经内膜增生程度轻于模型组。DPN造模成功后,模型组血糖高于正常对照组(P<0.05),复方芪鹰颗粒低、中、高剂量组血糖与模型组比较,差异无统计学意义(P>0.05)。药物干预4周后,模型组血糖高于正常对照组,复方芪鹰颗粒低、中、高剂量组血糖低于模型组,复方芪鹰颗粒中、高剂量组血糖低于复方芪鹰颗粒低剂量组(P<0.05)。模型组坐骨神经组织GRP78、p-PERK、ATF4、CHOP、caspase-3高于正常对照组,Nrf2�
Objective To investigate the mechanism of Compound Qiying Granules on diabetic peripheral neuropathy(DPN)rats based on PERK/Nrf2 pathway.Methods A total of 72 SPF male Wistar rats weight 180-220 g and aged eight weeks were divided into normal control group,model group,positive drug group,and Compound Qiying Granules low-dose,medium-dose,high-dose groups by random number table method,with 12 rats in each group.Except the normal control group,the other five groups were continuously fed high-fat diet,and streptozotocin(30 mg/kg)was injected eight weeks later,and then rats with fasting blood glucose>11.1 mol/L were selected to continue high-fat diet for four weeks to build DPN model.After the DPN modeling was successful,Compound Qiying Granules low-dose,medium-dose,high-dose groups were given 1.17,2.34,4.68 g/kg Compound Qiying Granules,respectively,the positive drug group was given Trimethylamine Oxide(110 mg/kg),2 ml/time,once a day,the normal control group and model group were given the same amount of double steaming water.After four weeks of intervention,blood glucose changes before and after intervention in the six groups were compared,and hematoxylin-eosin staining of sciatic nerve in the six groups was observed.Glucose regulatory protein 78(GRP78),protein kinase RNA-like endoplasmic reticulum kinase(PERK),phosphorylated PERK(p-PERK),activating transcription factor 4(ATF4),nuclear factor-erythroid 2-related factor 2(Nrf2),C/EBP homologous protein(CHOP),cysteine aspartic acid specific protease-3(caspase-3)in six groups of sciatic nerves were detected by Western blot.Results In the normal control group,the structure of myelinated nerve fibers was complete,the distribution was uniform,the arrangement was regular,the shape and structure of axons,myelin sheath,and nerve membranes were good and complete,and the shape and structure of endoneurals were normal.In the model group,there were loss and decrease of myelinated nerve fibers,partial disordered arrangement,partial axonal degeneration,segmental demyelination,thic
作者
陈臣
胡燕
刘涛
胡晓灵
CHEN Chen;HU Yan;LIU Tao;HU Xiaoling(The Fourth Clinical Medical College,Xinjiang Medical University,Xinjiang Uygur Autonomous Region,Urumqi830011,China;Xinjiang Uygur Autonomous Region Hospital of Traditional Chinese Medicine,Xinjiang Uygur Autonomous Region,Urumqi830000,China)
出处
《中国医药导报》
CAS
2023年第27期7-11,共5页
China Medical Herald
基金
国家自然科学基金资助项目(81960844)
中国博士后科学基金面上资助二等项目(2020M673545)。
