吉非替尼对糖尿病大鼠胰岛素敏感性的影响  

Gefitinib improves insulin sensitivity in wistar diabetes rats models

作　　者：孙琦[1] 王胜男[1] 李玉秀[1] 王姮[1] 

机构地区：[1]中国医学科学院北京协和医学院北京协和医院内分泌科卫生部内分泌重点实验室,100730

出　　处：《中华医学杂志》2009年第48期3441-3443,共3页National Medical Journal of China

摘　　要：目的探讨吉非替尼对2型糖尿病鼠胰岛素敏感性的影响及其相关机制。方法高糖高脂饲料喂养大鼠1个月后腹腔注射链脲霉素制成2型糖尿病鼠模型，分为生理盐水对照组、吉非替尼低剂量组（12．5mg／kg）和高剂量（25mg／kg）组、各干预8d测量给药前、后以及停药7d后大鼠的体重、空腹血糖和基础胰岛素水平；第二轮给药后留取肝脏组织，提取RNA进行半定量逆转录-聚合酶链反应比较胰岛素受体底物-1（IRS-1）和磷酸酰肌醇3激酶（P13K）基因的表达。结果成功建立2型糖尿病鼠模型，高剂量干预组大鼠的胰岛素敏感指数（ISI）较对照组显著增高（2．96±1．38比0．92±0．20，P〈0．05），低剂量组和高剂量组差异无统计学意义（2．95±1．51比2．96±1．38，P〉0．05）；停药7d后IsI无明显变化（2．03±0．72比2．99±0．63，P〉0．05）；3组大鼠体重改变差异无统计学意义（P〉0．05）；肝脏组织内IRS-1基因的表达对照组显著高于干预组[（6．3±2．4）％比（3．3±1．5）％，（3．2±1．8）％，P〈0．05]，低剂量组和高剂量组间差异无统计学意义（P〉0．05）；P13K基因的表达干预组显著高于对照组[（1．27±0．73）％，（1．43±0．71）％比（0．41±0．24）％，P〈0．05]，低剂量组和高剂量组间差异无统计学意义（P〉0．05）。结论吉非替尼可以改善2型糖尿病鼠的胰岛素敏感性，停药2个半衰期之后该改善作用仍然存在。可能与增强胰岛素信号传导的P13K／Akt途径相关，与体重无明显相关性。Objective To investigate the effect of Gefitinib on insulin sensitivity in rats of type-2 diabetes and its mechanism. Methods Normal Wistar rats were fed with high sucrose-fat diet for 1 month and then injected intraperitoneally with streptozotocin （STZ）. The rats satisfying the definity of type-2 diabetes were divided into 3 groups and given control solution （0. 9% NaCl） , low-dose Gefitinib and high-dose Gefitinib for 8 days, respectively. Body weights, FBG and FINS were recorded before, just after and 7 days after administration, respectively. After the second round of administration executed the rats and got the livers from rats. Compared the expression of insulin receptor substrate-1 （ IRS-1 ） and phosphatidylinositol-3-kinase （PI3K） genes in liver among the 3 groups with semi-quantitative Reverse Transcription-Polymerase Chain Reaction（PCR）. Results Normal Wistar rats fed with high sucrose-fat diet for 1 month and then injected intraperitoneally with STZ could establish type-2 diabetes model. After administration,insulin sensitivity index （ISI） of Gefitinib groups were significantly increased compared with control group（2.96 ±1.38 vs 0.92 ± 0. 20 ,P 〈0. 05）. There Were no significant difference between the two dose groups（2. 95 ± 1.51 vs 2. 96 ± 1.38, P 〉 0. 05）. 7 days after administration, the improved ISI did not change （2. 03 ± 0. 72 vs 2. 99 ± 0. 63,P 〉0. 05）. Body weights of the 3 goups had no significant difference. The expression of IRS-1 gene significantly decreased in Gefitinib groups compared with control group [ （ 3.3 ± 1.5 ） % vs （ 6. 3 ± 2.4 ） % P 〈 0. 05 ] and with no obvious difference between the two dose groups [ （ 3.3 ± 1.5 ） % vs （ 3.2 ± 1.8 ） % , P 〉 0. 05 ] , while the expression of PI3K gene significantly increased in Gefitinib groups compared with control group [ （ 1.27 ± 0. 73） % vs （0.41 ± 0. 24 ） %, P 〈 0. 05 ] also with no obvious difference between the two dose groups [ （ 1.27 ± 0. 73 ） % vs

关 键 词：糖尿病 吉非替尼 胰岛素受体底物-1 磷酸酰肌醇3激酶 

分 类 号：R587.1[医药卫生—内分泌] R979.1[医药卫生—内科学]