丙戊酸钠通过SKAP2/NF-κB通路对糖尿病小鼠胰岛β细胞的作用研究  

Effects of sodium valproate on pancreatic islet β cells in diabetic mice via SKAP2/NF-κB pathway

作　　者：杨靖[1] 吴小娟 肖能[1] 欧阳纯 孙玲 YANG Jing;WU Xiaojuan;XIAO Neng;OUYANG Chun;SUN Ling(Department of Pediatric Neuroendocrinology,Chenzhou First People's Hospital,Chenzhou 423000,Hunan Province,China)

机构地区：[1]郴州市第一人民医院儿童神经内分泌科,湖南郴州423000

出　　处：《世界临床药物》2022年第8期1019-1026,共8页World Clinical Drug

摘　　要：目的 研究丙戊酸钠对糖尿病小鼠胰岛β细胞的作用及对SKAP2/NF-κB通路表达的影响。方法 将75只雄性C57BL/6J小鼠随机分为5组:正常组,模型组,低剂量丙戊酸钠组(200 mg·kg^(-1)·d^(-1)),高剂量丙戊酸钠组(400 mg·kg^(-1)·d^(-1)),阳性对照组(二甲双胍,200 mg·kg^(-1)·d^(-1))。除正常组小鼠,其余小鼠给予连续5 d的50 mg/kg的链脲佐菌素溶液,以构建糖尿病模型,后续灌胃治疗持续5周。测定血浆胰岛素、空腹血糖和口服葡萄糖糖耐量,苏木精-伊红染色检测胰腺病理变化,TUNEL检测β细胞凋亡,蛋白免疫印迹检测胰腺Src激酶相关磷蛋白2(Src kinase-associated phosphoprotein 2,SKAP2)、核因子κB(nuclear factor-κB,NF-κB)p65、C/EBP同源蛋白(C/EBP-homologous protein,CHOP)、半胱氨酸天冬氨酸蛋白酶3(Caspase-3)的表达。结果 与正常组相比,模型组空腹血糖升高,耐糖水平和血浆胰岛素降低,胰腺损伤和β细胞凋亡率显著增加,胰腺组织中NF-κB p65、Caspase-3、CHOP表达明显升高,SKAP2表达显著降低(P<0.01);与模型组相比,三组治疗组上述检测指标均显著改善,且丙戊酸钠组呈现一定的量效关系。结论 丙戊酸钠可调节糖尿病小鼠的胰岛β细胞,其机制可能与SKAP2/NF-κB通路相关。Objective To study the effects of sodium valproate on pancreatic islet β cells and SKAP2/ NF-κB pathway in diabetic mice.Methods Seventy-five male C57BL/6J mice were randomly divided into 5 groups:normal group,model group,low-dose sodium valproate group(200 mg·kg^(-1)·d^(-1)),high-dose sodium valproate group (400 mg·kg^(-1)·d^(-1)),positive control group (metformin,200 mg·kg^(-1)·d^(-1)).Except for the normal group,the other mice were given streptozotocin (STZ,50 mg/kg) solution for 5 consecutive days to establish a diabetes model,and the subsequent intragastric treatment lasted for 5 weeks.Plasma insulin,fasting blood glucose and oral glucose tolerance were determined.Hematoxylin-eosin (HE) was used to detect pancreatic pathological changes.TUNEL was used to detect β-cell apoptosis.Western blot was used to detect pancreatic Src kinase-associated phosphoprotein 2 (SKAP2),nuclear factor-κB (NF-κB) p65,C/EBP-homologous protein (CHOP) and Caspase-3 express.Results Compared with the normal group,the fasting blood glucose was increased,glucose tolerance level and plasma insulin level of the model group were decreased,pancreatic injury and β-cell apoptosis rate were significantly increased,and expression of NF-κB p65,caspase-3 and CHOP in pancreatic tissue were significantly increased,and the expression of SKAP2 was significantly decreased (P<0.01).Compared with the model group,the above detection indexes in the three treatment groups were significantly improved,and the sodium valproate group showed a certain dose-effect relationship.Conclusion Sodium valproate can regulate islet β cells in diabetic mice,and the mechanism may be related to the SKAP2/NF-κB pathway.

关 键 词：丙戊酸钠 SKAP2/NF-κB通路 糖尿病 Β细胞 

分 类 号：R966[医药卫生—药理学]