吡格列酮对多囊卵巢综合征大鼠胰岛素抵抗的影响

Effect of pioglitazone on insulin resistance in rats with polycystic ovary syndrome

目的研究吡格列酮通过磷脂酞肌醇-3激酶/蛋白激酶B(PI3K/AKT)信号通路对多囊卵巢综合征大鼠胰岛素抵抗的影响。方法将30只雌性SD大鼠随机分为空白组、模型组和实验组,每组10只。空白组大鼠给予双蒸水并喂以普通饲料,模型组和实验组用高脂饮食喂养,同时给予来曲唑构建多囊卵巢综合征胰岛素抵抗(Polycystic ovary syndrome insulin resistance,PCOS-IR)大鼠模型。建模成功后,实验组大鼠给予吡格列酮20 mg·kg^(-1),灌胃;模型组和空白组大鼠分别给予生理盐水20 mL·kg^(-1)·d^(-1),灌胃。用放射免疫法(RIA)测定大鼠血清睾酮(T)、卵泡刺激素(FSH)、黄体生成素(LH)的水平;用自动生化分析仪测定大鼠空腹血糖(FBG)水平;用酶联免疫吸附(ELISA)法检测大鼠血清空腹胰岛素(FINS)水平;用抗胰岛素性稳态模式评估法评估大鼠胰岛素抵抗指数(HOMA-IR);用蛋白质印迹(Western blot)法检测PI3K磷酸化蛋白(p-PI3K)及AKT磷酸化蛋白(p-AKT)的表达。结果空白组、模型组和实验组大鼠血清T水平分别为(0.28±0.17),(3.82±0.79),(1.74±0.99)ng·mL^(-1);FSH水平分别为(4.08±1.36),(5.98±1.42),(4.51±0.94)mU·mL^(-1);LH水平分别为(3.18±0.84),(10.21±3.94),(6.77±0.40)mU·mL^(-1);FBG水平分别为(4.39±1.50),(7.21±1.54)和(5.97±0.70)mmol·L^(-1);血清FINS分别为(21.85±5.38),(56.42±7.21),(42.43±7.01)mU·L^(-1);HOMA-IR分别为3.84±2.48,15.02±6.42,8.56±1.78;以上指标,空白组与模型组比较,模型组和实验组比较,差异均有统计学意义(均P<0.05)。结论吡格列酮可有效降低PCOS-IR大鼠血清T、FSH、LH、FBG及FINS水平,从而改善多囊卵巢综合征大鼠的胰岛素抵抗。

Objective To explore the effect of pioglitazone on insulin resistance in rats with polycystic ovary syndrome through the phospholipidinositol-3 kinase/protein kinase B(PI3 K/AKT) signaling pathway. Methods Thirty female SD rats were randomly divided into blank group, model group and test group, with 10 rats in each group. The rats in blank group were given double distilled water and fed with ordinary feed. Model group and test group were fed with high-fat diet, and given letrozole to construct polycystic ovary syndrome insulin resistance(PCOS-IR) rat model. After successful modeling, the rats in test group were given pioglitazone(20 mg·kg-1) by gavage;rats in model group and blank group were given normal saline(20 mL·kg-1·d-1)by gavage. The fasting blood glucose( FBG) level of rats was measured with automatic biochemical analyzer,radioimmunoassay( RIA) was used to determine the levels of serum testosterone( T),follicle stimulating hormone( FSH) and luteinizing hormone( LH),the fasting blood glucose( FBG) level of rats was measured with blood glucose meter. Enzyme linked immunosorbent assay( ELISA) was performed to detect the fasting insulin( FINS) level in the serum of rats. The Homeostasis model assessment of insulin resistance was used to evaluate the rat insulin resistance index( HOMA-IR). Western blot was used to detect the expressions of PI3 K phosphorylated( p-PI3 K) protein and AKT phosphorylated( p-AKT) protein. Results In the blank group,model group and test group,the serum T levels were( 0. 28 ± 0. 17),( 3. 82 ± 0. 79),( 1. 74 ± 0. 99) ng·m L-1;FSH levels were( 4. 08 ± 1. 36),( 5. 98 ± 1. 42),( 4. 51 ± 0. 94) m U·m L-1;LH levels were( 3. 18 ± 0. 84),( 10. 21 ± 3. 94),( 6. 77 ± 0. 40) m U·m L-1;the FBG levels were( 4. 39 ± 1. 50),( 7. 21 ± 1. 54) and( 5. 97 ± 0. 70) mmol · L-1;serum FINS were( 21. 85 ± 5. 38),( 56. 42 ± 7. 21) and( 42. 43 ± 7. 01) m U·L-1;HOMA-IR were 3. 84 ± 2. 48,15. 02 ± 6. 42 and 8. 56 ± 1. 78. In terms of the above indicators,the differences between blank group and model group,between the model group and the test group were statistically significant( all P < 0. 05). Conclusion Pioglitazone can effectively reduce the levels of T,FSH,LH,FBG and FINS in PCOS-IR rats,thereby improving insulin resistance in rats with polycystic ovary syndrome.