坎地沙坦对高脂饮食大鼠脂肪组织中两面神激酶2和蛋白酪氨酸磷酸酶-1B表达的影响  

Effects of candesartan on expressions of JAK2 and PTP-1B in adipose tissue of high-fat diet-fed rats

作　　者：闫文华[1] 潘长玉[1] 窦京涛[1] 马芳玲[1] 王雪岷[1] 杨国庆[1] 王先令[1] 母义明[1] 陆菊明[1] 

机构地区：[1]解放军总医院内分泌科,北京100853

出　　处：《中华医学杂志》2010年第26期1836-1840,共5页National Medical Journal of China

基　　金：国家自然科学基金（30671095）

摘　　要：目的 观察坎地沙坦对高脂饮食大鼠脂肪组织两面内神激酶2（JAK2）和蛋白酪氨酸磷酸酶1B（PTP-1B）的影响.方法 45只雄性Wistar大鼠分为3组：正常对照组（NC）、高脂饮食组（HF）、高脂＋坎地沙坦组（FC）.FC组每天灌胃坎地沙坦8 mg/kg,其他两组分别给予等量生理盐水.16周后测定血清生化、胰岛素,行高胰岛素-正常葡萄糖钳夹实验,评价外周胰岛素抵抗程度.以RT-PCR方法和Western免疫印迹比较3组脂肪组织内JAK2和PTP-1B的mRNA和蛋白表达.结果 （1）HF组大鼠体重、肾周脂肪重量均明显高于NC和FC组（均P〈0.05）.（2）FC组总胆固醇、空腹胰岛素水平明显低于HF组[总胆固醇,FC组：（1.37 4±0.39）mmol/L,HF组：（2.01±0.26）mmol/L.P〈0.05;空腹胰岛素,FC组：（3.03±1.37）mU/L,HF组：（4.76±2.75）mu/L,P〈0.05],但胰岛素敏感指数及血管紧张素Ⅱ（AngⅡ）明显高于HF组[胰岛素敏感指数,FC组：（58±12）×10^-3.HF组：（29±9）×10^-3,P〈0.05;血管紧张素Ⅱ,FC组：（61±11）mmol/L,HF组：（52±10）mmol/L,P〈0.05].（3）FC组稳态葡萄糖输注率较HF组明显增高[FC组：（22±5）mg·kg^-1·min^-1,HF组：（14±4）mg·kg^-1·min^-1,P〈0.05].（4）与HF组相比,FC组脂肪JAK2和PTPT-1B的mRNA和蛋白水平明显降低.结论 高脂饮食诱导的肥胖大鼠存在胰岛素抵抗并且JAK2和PTP-1B表达明显增高,二者均与AngⅡ升高有关,而坎地沙坦能逆转这种变化.Objective To observe the effects of candesartan on the expressions of JAK2 and protein tyrosine phosphatase-1 B （PTP-1B） in adipose tissue of obese rats induced by high-fat diet Methods A total of 45 male Wistar rats were randomly assigned into 3 groups of normal control （ NC group）, high fat diet （HF group） and high-fat diet with daily Candesartan treatment （FC group）. The rats of FC group were treated with orally taken Candesartan at a dose of 8 mg/kg body weight per day. Blood chemistry and insulin were assayed at Week 16. Euglycemic-hyperinsulinemic clamp technique was performed to evaluate the peripheral insulin resistance. The expressions of JAK2 and PTP-1B in adipose tissue were confirmed by both reverse transcription-polymerase chain reaction （RT-PCR） and Western blot Results （1）The body weight and peri-renal fat weight of HF group were significantly higher than those of FC and NC groups （all P 〈0.05）. （2）total cholesterol （TC） and fasting insulin （FINS） of FC group were lower than those of HF group [TC,FC group：（1.37 ±0.39） mmol/L vs HF group：（2. 01 ±0. 26）mmol/L, P〈0.05; FINS,FC group： （3. 03 ± 1. 37） mU/L vs HF group： （4.76 ± 2. 75） mU/L, P 〈 0. 05] while insulin sensitive index （ISI） and angiotensin Ⅱ（ AngⅡ ） of FC group were much higher than those of HF group [ ISI, FC group： （58 ±12） × 10^-3 vs HF group： （29 ±9） × 10^-3, P〈0.05; Ang Ⅱ , FC group： （61 ±11） mmol/L vs HF group： （52 ±10） mmol/L, P 〈0. 05]. （3） The steady-state glucose infusion rate （SSGIR） of FC group was significantly higher than that of HF group [FC group： （22 ±5） mg · kg^-1 · min^-1 vs HF group： （ 14 ± 4 ） mg · kg^-1 · min ^-1, P 〈 0. 05 ]. （4） Both the mRNA and protein expressions of JAK2 and FTP-1B in FC group were significantly lower than those in HF group respectively. Conclusion There are insulin resistance and a high expression of JAK2 and PTP-1B in adipose tissue of obese rat

关 键 词：胰岛素抗药性 肥胖症 坎地沙坦 

分 类 号：R965[医药卫生—药理学]