小檗碱调控PI3K/AKT信号通路干预糖尿病动脉硬化的实验研究  

The Experimental Research of Berberine Intervening Diabetic Atherosclerosis by Regulating PI3K/AKT Signal Pathway

作　　者：朱昌国 李帅 孙艳君 王玉涛 孙岩 ZHU Changguo;LI Shuai;SUN Yanjun(Jinan People's Hospital,Shandong Jinan 271100,China)

机构地区：[1]山东省济南市人民医院全科医学科,山东济南271100 [2]山东省济南市中医医院周围血管病科,山东济南250012 [3]山东第一医科大学附属省立医院血管外科,山东济南250021

出　　处：《河北医学》2020年第12期1937-1942,共6页Hebei Medicine

基　　金：山东省自然科学基金资助项目,(编号:ZR2017MH038);山东省中医药科技发展计划,(编号:2019-0303);山东省医药卫生科技发展计划,(编号:2018WS478);山东省医药卫生科技发展计划,(编号:2018WS273);济南市第二届优秀卫生计生人才培养项目,(编号:济卫科外发[2018]8号);济南市第三批“薪火传承231工程”培养项目,(编号:济中医药发[2017]11号);济南市卫生健康系统青年岗位能手培养项目,(编号:济卫发[2019]1号);济南市卫生健康委员会科技计划项目,(编号:2019-1-23)。

摘　　要：目的:探讨PI3K/AKT信号通路在糖尿病模型大鼠腹主动脉中的表达变化和小檗碱的干预机制。方法:将SD大鼠随机分为空白对照组、糖尿病模型组和小檗碱干预组,每组20只,采用链脲佐菌素腹腔注射的方法构建糖尿病大鼠模型,造模成功后,按100mg·kg^-1·d^-1的剂量给予小檗碱干预组大鼠小檗碱溶液灌胃,空白对照组和糖尿病模型组大鼠给予相同剂量生理盐水灌胃,灌胃6周后,取出腹主动脉,利用免疫组化技术检测腹主动脉中PI3K、AKT、p21的表达水平,并对比干预前后各组大鼠血糖和血脂水平。结果:造模后,糖尿病模型大鼠血糖水平升高,药物干预后,小檗碱组大鼠血糖水平较治疗前降低,低于糖尿病模型组;各组大鼠TC、TG治疗前后以及组间比较差异无显著统计学意义;糖尿病模型大鼠腹主动脉PI3K、AKT的表达水平显著增加,p21的表达水平显著减少,小檗碱可降低糖尿病模型大鼠血糖水平,抑制腹主动脉PI3K、AKT并上调p21的表达。结论:PI3K/AKT信号通路的激活可能是DA发生的机制之一,BBR可能会通过调控PI3K/AKT信号通路,发挥抑制细胞增殖等作用,干预糖尿病动脉硬化发病。Objective:To investigate the expression level of PI3K/AKT signal pathway in the abdominal aorta of diabetic rats and the intervention mechanism of berberine.Methods:The SD rats were randomly divided into 3 groups,the normal control group,diabetic model group and berberine intervention group,20 rats in each group.The diabetic rat model was established by intraabdominal injection of streptozotocin.The rats in berberine intervention group received berberine gastric perfusion with the dosage of 100mg·kg^-1·d^-1 while other 2 groups with the same dosage of normal saline after the model were established successfully.After 6 weeks,the blood glucose and lipid level were compared before and after intervention.The abdominal aorta were taken out and the PI3K,AKT,p21 expression level were detected by immunohistochemical technique.Results:The blood glucose level of diabetic model rats increased after modeling.The blood glucose level of the berberine intervention group decreased after pharmacological intervention and lower than that of the diabetic model group.There was no statistically significant difference of TC and TG between 3 groups before and after intervention.The expression level of PI3K,AKT in abdominal aorta were significant high while the level of p21 was low in the diabetic model group.BBR could decrease the level of blood glucose and inhibit the expression of PI3K,AKT while upregulating the level of p21 in abdominal aorta of diabetic rats.Conclusion:The activation of PI3K/AKT signal pathway may be one of the pathogenesis of DA.BBR may intervene the pathogenesis of DA by inhibiting cell proliferation by regulating the PI3K/AKT signal pathway.

关 键 词：糖尿病动脉硬化 PI3K/AKT信号通路 小檗碱 

分 类 号：R285.5[医药卫生—中药学]