降糖消脂片对KK-A^y转基因小鼠胰岛素抵抗的影响  

Effect of Jiangtang Xiaozhi Tablet on Insulin Resistance KK-A^y Transgenic Mice Model of Diabetes Mellitus

作　　者：葛争艳[1] 金龙[1] 杨斌[1] 董小霞[1] 李宏坤[1] 郭宇洁[1] 任烨[1] 洪晓华[1] 王杨慧[1] 刘建勋[1] GE Zheng-yan JIN Long YANG Bin DONG Xiao-xia LI Hong-kun GUO Yu-jie REN Ye HONG Xiao-hua WANG Yang-hui LIU Jian-xun(Institute of Basic Medical Sciences, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing Municipal Key Laboratory of Phar- macology of Chinese Materia Medica, Beijing （100091)

机构地区：[1]中国中医科学院西苑医院基础医学研究所中药药理北京市重点实验室,北京100091

出　　处：《中国中西医结合杂志》2017年第3期331-337,共7页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：科技部重大新药创制项目(No.2010ZX09102-213;No.2012ZX09103201-040)

摘　　要：目的观察降糖消脂片对KK-A^y转基因小鼠稳态模型评估胰岛素抵抗指数(homeostasis model assessment for insulin resistance index,HOMA-IR)、胰岛素敏感指数(insulin sensitivity index,ISI)、胰腺组织胰岛素(insulin,INS)及胰岛素受体(insulin receptor,InsR)蛋白表达的影响。方法采用高脂饲料喂养KKAy转基因小鼠,制备糖尿病肥胖小鼠模型。同时选取11只同龄C57小鼠作为正常对照。将成模的55只KK-A^y小鼠采用随机数字表法分为模型组、吡格列酮组(8 mg/kg)、降糖消脂片高、中、低剂量组(分别给予降糖消脂片10、5、2.5 g生药/kg),每组11只。以上各组均灌胃给药,正常对照组及模型组灌胃等体积灭菌水,每日1次,连续8周。给药8周后,称体重并测随机血糖(random blood glucose,RBG);眼静脉丛取血,测定INS、TC及TG水平,计算HOMA-IR及ISI;取胰腺进行形态学观察;采用免疫组化方法检测胰腺组织INS及InsR表达;采用免疫印迹(Western blot)法检测胰腺胰岛素受体β(insulin receptorβ,InsRβ)及胰岛素受体底物1(insulin receptor substrate 1,IRS-1)蛋白表达水平。结果与正常对照组比较,造模后各组小鼠出现肥胖,血糖及血脂明显升高(P<0.01)。给药8周后模型组小鼠体重增加(P<0.01),血糖及血脂稳定在高位水平;与模型组比较,降糖消脂片各剂量组小鼠体重、TG、INS及HOMA-IR水平明显降低(P<0.05,P<0.01);且高剂量组RBG降低更明显(P<0.01);降糖消脂片高、低剂量组小鼠ISI明显升高(P<0.05,P<0.01)。胰腺病理HE染色结果显示,模型组胰岛萎缩,胰岛数目明显减少,分布稀疏,胰岛密度减低,胰岛细胞代偿性肥大,空泡变性,并可见凋亡细胞,表现为胞浆肿胀,核固缩。降糖消脂片高、中剂量组胰岛细胞数目明显增多,变性及凋亡细胞减少。免疫组化结果显示,与正常对照组比较,模型组INS及InsR累积光密度(IOD)值明显降低(P<0.01);与模型组比较,降糖消脂片各剂量组胰腺INS及IObjective To observe effects of Jiangtang Xiaozhi Tablet （JTXZT） on homeostasis model of assessment for insulin resistance index （ HOMA-IR）, insulin sensitivity index （ISI）, expressions of insulin （ INS） and insulin receptor （ InsR） in pancreas tissues of KK-Ay transgenic mice model of diabetes mellitus （ DM）. Methods KK-AYtransgenic mice were fed with high fat forage to induce hyper-glycemic obese DM model. The C17 mice at same age were used as a normal control group （fed with e- qual volume of sterile water, n = 11 ）. Successful modeled 55 mice with DM obesity were divided into 5 groups by random digit table （11 in each group）, including the model group （fed with equal volume of sterile water, with no treatment）, the Pioglitazone Hydrochloride Tablet treatment group （8 mg/kg; as a posi- tive control group）, and JTXZT groups [high （10.0 g crude drugs/kg）, middle （5.0 g crude drugs/kg） and low dose （2.5 g crude drugs/kg） ]. All medications were fed by gastrogavage, once per day for 8 successive weeks. All mice were weighed and levels of random blood glucose （RBG） determined after 8 weeks of treatment. Blood was collected from ophthalmic vein. Levels of insulin （ INS）, serum total cholesterol （TC） and triglyceride （TG） were detected. HOMA-IR and ISI were calculated. The morphological changes of pancreas tissues were extracted for performed pathological examinations. The expressions of INS and insulin receptor （InsR） were measured by immunohistochemistry （IHC）. Expressions of insulin receptor13 （InsR13） and insulin receptor substrate-1 （IRS-1） in pancreas tissues were detected using Western blot. Results Compared with the normal control group, obesity, obviously increased blood glucose and blood lipids occurred in each group after modeling （P 〈0.01 ）. After 8 weeks of medication mice in the model group had put up body weight （P 〈0.01）, blood glucose and blood lipids were kept on quite higher levels. Compared with the mod

关 键 词：降糖消脂片 KK-AY小鼠 胰岛素抵抗指数 胰岛素敏感指数 胰岛素受体β 胰岛素受体底物-1 

分 类 号：R587.1[医药卫生—内分泌]