姜黄素调控NF-κB信号通路对糖尿病模型大鼠胰岛细胞形态和功能的影响  

Effects of curcumin regulating NF-κB signal pathway on morphology and function of pancreatic islet cells in diabetes model rats

作　　者：刘虎军[1] 贾菲 贺钰梅[2] LIU Hujun;JIA Fei;HE Yumei(Department of Pharmacy,Affiliated Hospital of Yan'an University,Yan'an 716000,China;Department of General Medicine,Affiliated Hospital of Yan'an University,Yan'an 716000,China)

机构地区：[1]延安大学附属医院药剂科,陕西延安716000 [2]延安大学附属医院全科医学科,陕西延安716000

出　　处：《药物评价研究》2023年第4期803-811,共9页Drug Evaluation Research

基　　金：延安市科学技术局资助项目(2018CGZH-15)。

摘　　要：目的探讨姜黄素通过核因子-κB(NF-κB)信号通路对高糖高脂饮食诱导的糖尿病模型大鼠胰岛细胞形态和功能的影响。方法采用高糖高脂饲料+ip链脲佐菌素法制备糖尿病大鼠模型,将模型成功SD大鼠随机分为5组:模型组、二甲双胍(200 mg·kg^(−1),阳性药)组和姜黄素低、中、高剂量(50、150、250 mg·kg^(−1))组,对照组不造模。ig给药,每天1次,连续6周,对照组同时注射等量无菌磷酸盐缓冲液(PBS)。观察SD大鼠体质量变化;血糖仪检测空腹血糖;ELISA法检测血清C肽水平;生化分析仪检测血清中糖化血红蛋白、三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆红素(TBil)、血肌酐(Scr)、血尿素氮(BUN)、尿酸(UA)水平;取胰腺进行HE染色,于光镜下观察胰岛形态学改变;免疫组化染色法观察胰岛NF-κB的阳性表达;Western blotting法检测NF-κB信号通路相关蛋白表达;提取胰岛细胞,免疫荧光染色观察胰岛素分泌,葡萄糖刺激的胰岛素分泌(GSIS)实验检测胰岛素分泌量。结果与模型组比较,各给药组体质量在治疗第2周时开始缓慢增长,第3、4周体质量显著升高(P<0.05);血糖水平显著降低(P<0.05),血清C肽水平显著升高(P<0.05);糖化血红蛋白、TG、TC、LDL-C、ALT、AST、Scr、BUN、UA水平显著降低(P<0.05),HDL-C水平显著升高(P<0.05);胰岛大小和形态逐渐恢复正常,胰岛细胞依次变得更清晰完整,导管系统内的囊性扩张也逐渐减少;NF-κB阳性细胞减少;p-P65蛋白表达显著降低(P<0.05),p-IκBα蛋白表达显著升高(P<0.05);胰岛原代细胞分泌胰岛素显著增加(P<0.05)。结论姜黄素可以保护糖尿病大鼠胰岛细胞正常形态,维持胰岛细胞功能,减轻糖尿病大鼠症状,其机制可能与调控NF-κB信号通路有关。Objective To investigate the effect of curcumin through NF-κB signaling pathway on the morphology and function of islet cells in diabetes mellitus rats induced by high glucose and high-fat diet.Methods The diabetes rat model was prepared by the method of high sugar and high fat diet+ip streptozotocin.The successfully modeled SD rats were randomly divided into five groups:the model group,metformin(200 mg·kg^(−1),positive drug)group,and low,medium,and high dose curcumin(50,150,250 mg·kg^(−1))groups.The control group was not modeled.The control group was injected with an equal amount of sterile phosphate buffer(PBS)once a day for six weeks.Observe the changes in body mass of SD rats;The fasting blood glucose was measured by a blood glucose meter.Serum C-peptide level was detected by ELISA.The serum levels of glycosylated hemoglobin,triacylglycerol(TG),total cholesterol(TC),low density lipoprotein cholesterol(LDL-C),high density lipoprotein cholesterol(HDL-C),alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBil),serum creatinine(Scr),blood urea nitrogen(BUN),and uric acid(UA)were measured by a biochemical analyzer.The pancreas was taken for HE staining,and the morphological changes of the islets were observed under light microscopy.Observation of islet positive expression of NF-κB by immunohistochemical staining.Detection of NF-κB signal pathway related proteins expression by Western blotting.Extract islet cells,observe insulin secretion by immunofluorescence staining,and detect insulin secretion by glucose stimulated insulin secretion(GSIS)experiment.Results Compared with the model group,the body mass of each treatment group began to slowly increase at the second week of treatment,and significantly increased at the third and fourth weeks(P<0.05).The level of blood glucose significantly decreased(P<0.05),while the level of serum C-peptide significantly increased(P<0.05).The levels of glycosylated hemoglobin,TG,TC,LDL-C,ALT,AST,Scr,BUN,and UA decreased significantly(P<0.05),while

关 键 词：姜黄素 核因子-κB(NF-κB) 糖尿病 胰岛细胞 胰岛素分泌 

分 类 号：R285.5[医药卫生—中药学]