酮替芬对2型糖尿病大鼠胰岛β细胞氧化应激的影响  

Effect of ketotifen on oxidative stress of pancreatic beta cells of type 2 diabetic rats

作　　者：陈咨苗[1] 倪连松[1] 王美荣[1] 潘亮亮[2] 胡万里[2] 

机构地区：[1]温州医学院附属第一医院内分泌科,浙江温州325000 [2]温州医学院温州医学院电镜中心,浙江温州325000

出　　处：《中国药理学与毒理学杂志》2013年第3期385-390,共6页Chinese Journal of Pharmacology and Toxicology

基　　金：温州市科技局基金资助(Y20100063)~~

摘　　要：目的探讨酮替芬对2型糖尿病大鼠胰岛β细胞氧化应激的影响及其作用机制。方法以高糖高脂饲料对SD大鼠饮食诱导6周,随后一次性ip给予链脲佐菌素制备糖尿病大鼠模型,每天ig给予酮替芬0.09mg·kg-1,持续8周。检测空腹血糖(FBG)、游离脂肪酸(FFA)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、白介素6(IL-6)、肿瘤坏死因子α(TNF-α);检测胰腺丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性,检测胰腺细胞线粒体细胞色素C氧化酶(CCO)、琥珀酸脱氢酶(SDH)活性,电镜观察组织形态。结果与正常对照组比较,模型组大鼠FBG水平显著升高(P<0.01),FFA,TG和LDL-C水平升高(P<0.05),IL-6,TNF-α水平升高(P<0.05),MDA含量增加(P<0.05),SOD,CCO和SDH活性下降(P<0.05),与模型组比较,给予酮替芬同步干预后,FBG水平下降〔(24.5±2.7)vs(15.9±1.9)mmo·l L-1〕,FFA,TG和LDL-C水平由1.03±0.23,2.89±0.56和(2.05±0.33)mmo·l L-1分别降低至0.71±0.15,2.36±0.40和(1.56±0.30)mmol·L-1,IL-6,TNF-α水平由(58.33±4.94)ng·L-1和(1.98±0.45)μg·L-1分别下降至(33.84±3.82)ng·L-1和(1.12±0.27)μg·L-1,MDA含量减少〔(1.12±0.20)vs(0.87±0.20)μmol.g-1,SOD,CCO和SDH活性由(28.55±4.06)kU·g-1,(13.00±1.14)mmo·l g-1和(3.75±0.44)kU·g-1分别增加到(31.34±2.59)kU·g-1,(15.87±1.64)mmol·g-1和(4.92±0.50)kU·g-1,电镜结果显示,酮替芬的干预使胰岛β细胞形态结构得到改善。结论酮替芬能够降低糖尿病大鼠炎症介质和游离脂肪酸水平,减轻氧化应激损伤,使胰岛细胞线粒体功能改善,实现对胰岛β细胞的保护作用。OBJECTIVE To investigate the effect and mechanism of ketotifen on oxidative stress of pancreatic beta cells in streptozotocin-induced type 2 diabetic rats.METHODS Male SD rats were fed with high-carbon hydrate-fat diet 6 weeks and ip given STZ to induce a type 2 diabetes model.Rats of ketotifen group were given ketotifen 0.09 mg·kg-1 for 8 weeks.The fasting blood glucose（FBG）,free fatty acid（FFA）,triglyceride（TG） and low density lipoprotein cholesterin（LDL-C）,interleukin-6（IL-6） and tumor necrosis factor-alpha（TNF-α） were analyzed,the content of malondialdehyde（MDA） and the activity of superoxide dismutase（SOD） in pancreatic tissue were measured,the activities of cytochrome C oxidase（CCO） and succinate dehydrogenase（SDH） in pancreatic cells mitochondria were tested,Histomorphology were observed by transmission electron microscope.RESULTS Compared with normal control group,FBG levels in diabetic rats significantly increased（P〈0.01）,FFA,TG and LDL-C levels in diabetic rats increased（P〈0.05）,IL-6 and TNF-α levels in diabetic rats increased（P〈0.05）,the content of MDA increased while the activites of SOD,CCO and SDH decreased（P〈0.05）.Compared with model group,ketotifen 0.09 mg·kg-1 suppressed serum glucose in diabetic rats to（15.9±1.9）mmol·L-1,and reduced FFA,TG and LDL-C levels to 0.71±0.15,2.36±0.40 and（.56±0.30）mmol·L-1.Ketotifen 0.09 mg·kg-1 could significantly decrease IL-6 and TNF-α levels to（33.84±3.82）ng·L-1 and（1.12±0.27）μg·L-1,reduced MDA content to（0.87±0.20）μmol·g-1,and increased the activites of SOD,CCO and SDH to（31.34±2.59）kU·g-1,（15.87±1.64）mmol·g-1 and（4.92±0.50）kU·g-1.Transmission electron microscope observation showed that beta cells morphological structure were improved by ketotifen.CONCLUSION Ketotifen has protective effects on pancreatic beta cells by reduction of inflammation medium and free fatty acid leves,alleviation of oxidative stress and improvement of islet cell mitoch

关 键 词：酮替芬 糖尿病 2型 胰岛Β细胞 氧化应激 

分 类 号：R587.1[医药卫生—内分泌]