利拉鲁肽对糖尿病骨质疏松症大鼠骨密度和胰岛素抵抗的影响

Effects of liraglutide on bone mineral density and insulin resistance in diabetic osteoporosis rats

目的 探究利拉鲁肽(LRG)对糖尿病骨质疏松症(DOP)大鼠骨密度及胰岛素抵抗的影响,及其作用机制。方法 从50只SD雌性大鼠中随机选取10只为空白组,其余大鼠建立DOP模型,4只大鼠建模失败,其余36只大鼠随机分为模型组及低、中、高剂量实验组,每组9只。低、中、高剂量实验组分别皮下注射0.6、1.2和1.8 mg·kg^(-1) LRG;空白组和模型组均皮下注射等量的0.9%NaCl溶液。5组大鼠均连续给药8周。用小动物体成分分析仪检测大鼠骨密度(BMD),计算稳态模型的胰岛素抵抗指数(HOMA-IR),用全自动生化仪检测血清中白细胞介素-1β(IL-1β)水平,用蛋白质印迹法检测Toll样受体4/髓分化因子88(TLR4/MyD88)蛋白的表达水平。结果 中、高剂量实验组和模型组、空白组的BMD分别为(0.21±0.05)、(0.25±0.04)、(0.15±0.03)和(0.28±0.07)g·cm^(-2),HOMA-IR分别为8.66±1.37、5.83±0.52、17.03±3.04和2.16±0.37,IL-1β分别为(481.28±21.11)、(295.49±18.46)、(882.67±43.12)和(95.86±9.59)ng·L^(-1),TLR4蛋白相对表达水平分别为0.49±0.05、0.37±0.04、0.88±0.09和0.28±0.03,MyD88蛋白相对表达水平分别为0.62±0.07、0.38±0.04、1.03±0.13和0.32±0.04。模型组的上述指标与中、高剂量实验组比较,差异均有统计学意义(均P<0.05)。结论 利拉鲁肽能够提高DOP大鼠的BMD,改善胰岛素抵抗和血清炎症因子水平,其作用机制可能与TLR4/MyD88通路有关。

Objective To explore the effects of liraglutide(LRG)on bone mineral density and insulin resistanceindiabetic osteoporosis(DOP)rats and its mechanism.Methods Ten rats were randomly selected from 50 female SD rats as blank group,the other rats were established DOP model,4 rats failed in modeling,and the other 36 rats were randomly divided into model group and experimental-L,-M,-H groups,with 9 rats in each group.Experimental-L,-M,-H groups were injected subcutaneously with 0.6,1.2 and 1.8 mg·kg^(-1 )LRG,respectively.The blank group and model group were injected with 0.9%Nacl solution subcutaneously.Five groups were treated for 8 weeks.Bone mineral density(BMD)was determined by small animal body composition analyzer,insulin resistance index(HOMA-IR)of homeostasis model was calculated.The serum interleukin-1β(IL-1β)level was detected by automatic biochemical analyzer,and the expression levels of Toll-like receptor 4/myeloid differentiation factor 88(TLR4/MyD88)protein were detected by Western blot.Results The BMD of the experimental-M,-H groups,model group and blank group were(0.21±0.05),(0.25±0.04),(0.15±0.03)and(0.28±0.07)g·cm^(2);HOMA-IR were 8.66±1.37,5.83±0.52,17.03±3.04 and 2.16±0.37;IL-1βwere(481.28±21.11),(295.49±18.46),(882.67±43.12)and(95.86±9.59)ng·L^(-1);TLR4 protein relative expression levels were 0.49±0.05,0.37±0.04,0.88±0.09 and 0.28±0.03;MyD88 protein relative expression levels were 0.62±0.07,0.38±0.04,1.03±0.13 and 0.32±0.04,respectively.Compared with model group,the above indexes in the experimental-M,-H groups were statistically significant(all P<0.05).Conclusion LRG can increase bone mineral density,improve bone metabolism,insulin resistance and serum inflammation in DOP rats,and its mechanism of action may be related to the TLR4/MyD88 pathway.