中华内科杂志
中華內科雜誌
중화내과잡지
CHINESE JOURNAL OF INTERNAL MEDICINE
2011年
9期
781-784
,共4页
宋璐璐%萧建中%杨文英%张敏%柳彬彬%潘琳
宋璐璐%蕭建中%楊文英%張敏%柳彬彬%潘琳
송로로%소건중%양문영%장민%류빈빈%반림
糖尿病,2型%胰高血糖素样肽-1%胰岛beta细胞
糖尿病,2型%胰高血糖素樣肽-1%胰島beta細胞
당뇨병,2형%이고혈당소양태-1%이도beta세포
Diabetes mellitus,type 2%Glucagon-like peptide-1%Islet beta-cell
目的 评价胰高血糖素样肽类似物利拉鲁肽与胰岛素增敏剂吡格列酮联合治疗db/db小鼠糖尿病的效果.方法 35只8周龄,体重(35.3±2.5)g的雄性db/db小鼠分为(1)对照组(n=8):给予生理盐水0.1 ml,2次/d;(2)吡格列酮组(n=9):给予吡格列酮(饲料中含0.02%吡格列酮)+生理盐水0.1 ml,2次/d;(3)利拉鲁肽组(n=9):给予利拉鲁肽300 mg/kg,2次/d;(4)联合治疗组(n=9):给予吡格列酮(饲料中含0.02%吡格列酮)+利拉鲁肽300mg/kg,2次/d.利拉鲁肽用灭菌生理盐水稀释后皮下注射,每天8:00和16:00给药,持续4周.行腹腔注射葡萄糖耐量试验(IPGTT)和胰岛素耐量试验(ITT),评价胰岛β细胞的增殖.采用单因素方差分析进行数据统计分析.结果 干预4周后,联合治疗组糖化血红蛋白(4.5±0.6)%,糖耐量试验血糖曲线下面积(1814±91)mmol·min·L-1,游离脂肪酸(202.0±20.4)μmol/L,TG(0.81±0.28)mmol/L均明显低于对照组[(7.3±0.4)%,(4042±183)mmol·min·L-1,(272.5±21.7)μmol/L,(1.35±0.21)mmol/L],P值均＜0.05;胰岛素曲线下面积(1639±372)μg·min·L-1,脂联素(16.7±2.0)mg/L,胰岛组织切片胰岛素阳性面积(59.5±1.5)%和胰岛新生β细胞比例(2.4±0.5)%均显著高于对照组[(834±201)μg·min·L-1,(10.2±1.8)mg/L,(22.4±1.5)%和(0.8±0.3)%],P值均＜0.05.且联合治疗组上述指标均低于或高于单药治疗组.联合治疗显著改善胰岛β细胞和α细胞分布,恢复正常的胰岛形态.结论 吡格列酮联合利拉鲁肽治疗相比单药更好地改善db/db小鼠糖脂代谢,保护胰岛β细胞功能并促进其增殖.
目的 評價胰高血糖素樣肽類似物利拉魯肽與胰島素增敏劑吡格列酮聯閤治療db/db小鼠糖尿病的效果.方法 35隻8週齡,體重(35.3±2.5)g的雄性db/db小鼠分為(1)對照組(n=8):給予生理鹽水0.1 ml,2次/d;(2)吡格列酮組(n=9):給予吡格列酮(飼料中含0.02%吡格列酮)+生理鹽水0.1 ml,2次/d;(3)利拉魯肽組(n=9):給予利拉魯肽300 mg/kg,2次/d;(4)聯閤治療組(n=9):給予吡格列酮(飼料中含0.02%吡格列酮)+利拉魯肽300mg/kg,2次/d.利拉魯肽用滅菌生理鹽水稀釋後皮下註射,每天8:00和16:00給藥,持續4週.行腹腔註射葡萄糖耐量試驗(IPGTT)和胰島素耐量試驗(ITT),評價胰島β細胞的增殖.採用單因素方差分析進行數據統計分析.結果 榦預4週後,聯閤治療組糖化血紅蛋白(4.5±0.6)%,糖耐量試驗血糖麯線下麵積(1814±91)mmol·min·L-1,遊離脂肪痠(202.0±20.4)μmol/L,TG(0.81±0.28)mmol/L均明顯低于對照組[(7.3±0.4)%,(4042±183)mmol·min·L-1,(272.5±21.7)μmol/L,(1.35±0.21)mmol/L],P值均＜0.05;胰島素麯線下麵積(1639±372)μg·min·L-1,脂聯素(16.7±2.0)mg/L,胰島組織切片胰島素暘性麵積(59.5±1.5)%和胰島新生β細胞比例(2.4±0.5)%均顯著高于對照組[(834±201)μg·min·L-1,(10.2±1.8)mg/L,(22.4±1.5)%和(0.8±0.3)%],P值均＜0.05.且聯閤治療組上述指標均低于或高于單藥治療組.聯閤治療顯著改善胰島β細胞和α細胞分佈,恢複正常的胰島形態.結論 吡格列酮聯閤利拉魯肽治療相比單藥更好地改善db/db小鼠糖脂代謝,保護胰島β細胞功能併促進其增殖.
목적 평개이고혈당소양태유사물리랍로태여이도소증민제필격렬동연합치료db/db소서당뇨병적효과.방법 35지8주령,체중(35.3±2.5)g적웅성db/db소서분위(1)대조조(n=8):급여생리염수0.1 ml,2차/d;(2)필격렬동조(n=9):급여필격렬동(사료중함0.02%필격렬동)+생리염수0.1 ml,2차/d;(3)리랍로태조(n=9):급여리랍로태300 mg/kg,2차/d;(4)연합치료조(n=9):급여필격렬동(사료중함0.02%필격렬동)+리랍로태300mg/kg,2차/d.리랍로태용멸균생리염수희석후피하주사,매천8:00화16:00급약,지속4주.행복강주사포도당내량시험(IPGTT)화이도소내량시험(ITT),평개이도β세포적증식.채용단인소방차분석진행수거통계분석.결과 간예4주후,연합치료조당화혈홍단백(4.5±0.6)%,당내량시험혈당곡선하면적(1814±91)mmol·min·L-1,유리지방산(202.0±20.4)μmol/L,TG(0.81±0.28)mmol/L균명현저우대조조[(7.3±0.4)%,(4042±183)mmol·min·L-1,(272.5±21.7)μmol/L,(1.35±0.21)mmol/L],P치균＜0.05;이도소곡선하면적(1639±372)μg·min·L-1,지련소(16.7±2.0)mg/L,이도조직절편이도소양성면적(59.5±1.5)%화이도신생β세포비례(2.4±0.5)%균현저고우대조조[(834±201)μg·min·L-1,(10.2±1.8)mg/L,(22.4±1.5)%화(0.8±0.3)%],P치균＜0.05.차연합치료조상술지표균저우혹고우단약치료조.연합치료현저개선이도β세포화α세포분포,회복정상적이도형태.결론 필격렬동연합리랍로태치료상비단약경호지개선db/db소서당지대사,보호이도β세포공능병촉진기증식.
ObjectivesTo evaluate the effect of combination of liraglutide,a glucagon-like peptide-1 analogue and pioglitazone,an insulin sensitizer,on diabetic db/db mice.Methods Thirty-five 8-week old male db/db mice were divided into control group (n = 8 ),pioglitazone group (n =9 ),liraglutide group (n =9) and combined therapeutic group (n =9),which was given normal saline 0.1 ml,2/d,pioglitazone 24 mg· kg-1 · d-1 (feed contained 0.02％ pioglitazone) + normal saline 0.1 ml,2/d,liraglutide 300 mg/kg,2/d,and pioglitazone 20 mg · kg-1 · d -1 ( feed contained 0.02％ pioglitazone) +liraglutide 300 mg/kg,2/d,respectively.Liraglutide were given at 8:00 and 16:00 via subcutaneous injection after having been diluted with sterilized normal saline.Effect on glucose,lipid metabolism and islet β-cell preservation were assessed after 4 weeks.Oneway ANOVA was adopted for statistical analysis.Results Combination therapy displayed promising anti-hyperglycemic[glycosylated hemoglobin Alc: (4.5 ± 0.6)％vs.(7.3 ±0.4)％,P ＜ 0.001].Glucose tolerance were improved assessed by area under curve(AUC) of glucose by intraperitoneal glucose tolerance test (IPGTT)[(1814 ±91 ) mmol · min · L-1 vs.(4042 ±183) mmol · min · L-1,P ＜0.001];insulin release response to glucose were also preserved as AUC of insulin by IPGTT was higher[( 1639 ±372) μg · min · L-1 vs.(834 ±201 )μg · min · L-1].Combination therapy also reduced circulated free fatty acids and TG[( 202.0 ± 20.4 ) μmol/L vs.( 272.5 ± 21.7 )μmol/L,(0.81 ± 0.28) mmol/L vs.( 1.35 ± 0.21 ) mmol/L],and increased plasma adiponectin [(16.7±2.0)mg/L vs.(10.2±1.8)mg/L].All P value ＜0.05.Islet immunohistochemistry showed that combination therapy significantly increased insulin positive area were[( 59.5 ± 1.5 ) ％ vs.( 22.4 ±1.5) ％]and ratio of Brdu positive β-cells was three folds than vehicle-treated mice[( 2.4 ± 0.5 ) ％ vs.(0.8 ±0.3)％],both greater than each single treatment.Combined therapy significantly improved islet β cell/α cell distribution,which led to islet recovery.Conclusions Combined therapy improves glucose and lipid metabolism,preserves islet β-cell function and stimulates β-cell proliferation,greater than either liraglutide or pioglitazone treatment alone.
