补阳还五汤调控PI3K/Akt自噬通路改善糖尿病周围神经病变的机制研究  

Study on the mechanism of buyang huanwu decoction to improve diabetic peripheral neuropathy by regulating PI3K/Akt autophagy pathway

作　　者：赵静[1] 张建[2] 胡爱民[2] 陶毅[1] 晏玲[2] ZHAO Jing;ZHANG Jian;HU Aimin;TAO Yi;YAN Ling(Department of Endocrinology,Hanyang Hospital,Wuhan Hospital of Traditional Chinese Medicine,Wuhan 430050,Hubei Province,China;Department of Endocrinology,Hankou Hospital,Wuhan Hospital of Traditional Chinese Medicine,Wuhan 430014,Hubei Province,China)

机构地区：[1]武汉市中医医院汉阳院区内分泌科,湖北武汉430050 [2]武汉市中医医院汉口院区内分泌科,湖北武汉430014

出　　处：《世界临床药物》2024年第1期18-25,共8页World Clinical Drug

基　　金：武汉市卫生和计划生育委员会资助项目(WZ18D08)。

摘　　要：目的 本研究旨在探究补阳还五汤通过磷脂酰肌醇3-激酶/蛋白激酶B(phosphatidylinositol 3-kinase/protein kinase B,PI3K/Akt)自噬通路对糖尿病周围神经病变(diabetic peripheral neuropathy,DPN)的保护作用。方法 48只Wistar大鼠分为对照组(灌胃+静脉注射等体积的无菌盐水溶液)、DPN模型组(灌胃+静脉注射等体积的无菌盐水溶液)、中药治疗组(灌胃2 g/kg补阳还五汤)及PI3K抑制剂组(2 g/kg补阳还五汤+静脉注射1.5 mg/kg PI3K抑制剂LY2940002)。除对照组外,其余3组诱发DPN大鼠模型后给予对应的药物治疗。观察坐骨神经传导指标和超微结构,分析血清因子表达水平及神经自噬、凋亡情况,检测相关蛋白表达水平。结果 与对照组比较,DPN模型组坐骨神经髓轴突严重丧失,髓鞘破坏和卷曲,细胞器减少,坐骨神经传导动作点位的速度和幅度均降低,细胞自噬、凋亡水平升高,且PI3K/Akt通路被抑制,差异具有统计学意义(P <0.01)。中药治疗组的上述指标治疗后较改善,包括超微结构变化,自噬、凋亡以及PI3K/Akt通路相关蛋白水平(P <0.01)。而PI3K抑制剂部分逆转补阳还五汤对DPN大鼠模型的保护作用(P <0.01)。结论 补阳还五汤可能通过激活PI3K/Akt通路抑制凋亡、自噬,进而对DPN大鼠发挥保护作用。Objective To investigate the protective effect of buyang huanwu decoction on diabetic peripheral neuropathy(DPN)through phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)autophagy pathway.Methods Forty-eight Wistar rats were grouped into control group(gavage+intravenous sterile saline solution of equal volume),DPN model group(gavage+intravenous sterile saline solution of equal volume),traditional Chinese medicine treatment group(gavage 2 g/kg buyang huanwu decoction)and PI3K inhibitor group(gavage 2 g/kg buyang huanwu decoction+intravenous 1.5 mg/kg PI3K inhibitor LY2940002).Except for the control group,DPN rats in the other three groups were given the corresponding drug treatment.The conduction index and the ultrastructure of the sciatic nerve were observed.Serum factor expression levels and neuronal autophagy and apoptosis was analyzed.Expression levels of relevant proteins were examined.Results Compared with the control group,the sciatic nerve myelin axons were severely lost in DPN model group,the myelin sheath was destroyed and curled,the organelles were reduced,the speed and amplitude of the sciatic nerve conduction action sites were decreased,the levels of autophagy and apoptosis were increased,and the levels of PI3K/Akt pathway was inhibited,and the differences were statistically significant(P<0.01).The above indexes were improved in the Chinese medicine treatment group,including ultrastructural changes,autophagy,apoptosis and PI3K/Akt pathway-related protein levels(P<0.01).However,PI3K inhibitor partially reversed the protective effect of buyang huanwu decoction on DPN rat model(P<0.01).Conclusion Buyang huanwu decoction may inhibit apoptosis and autophagy by activating the PI3K/Akt pathway,thereby exerting a protective effect on DPN rats.

关 键 词：补阳还五汤 磷脂酰肌醇3-激酶/蛋白激酶B通路 自噬 糖尿病周围神经病变 

分 类 号：R285.5[医药卫生—中药学]