有追赶生长的小于胎龄大鼠肿瘤坏死因子-α白细胞介素-6白细胞介素-1β水平及与胰岛素抵抗的相关性研究

Levels of tumor necrosis factor-α,interleukin-6,interleukin-1βin the rats born small for gestational age with catch-up growth and the relationships with insulin resistance

目的探讨有生长追赶的小于胎龄(SGA)大鼠肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)水平及与胰岛素抵抗的关系。方法应用孕鼠全程饮食限制法建立SGA大鼠模型。每周测量SGA组和对照组仔鼠体质量。测定SGA组和对照组仔鼠生后6周空腹血糖(FPG)及空腹胰岛素(FINS)水平,计算胰岛素抵抗指数(HOMAIR)。应用ELISA法测定血清和内脏脂肪组织中TNF-α、IL-6及IL-1β水平。结果SGA仔鼠平均出生体质量(5.11±0.26)g,明显低于对照组(6.98±0.62)g,差异有统计学意义(t=-15.066,P<0.05)。3周时平均体质量达到对照组水平,完成了追赶生长。6周时平均体质量较对照组明显增加,差异有统计学意义[(229.71±24.41)g与(209.89±27.35)g,t=2.662,P<0.05]。SGA组仔鼠FINS和HOMA-IR明显高于对照组[(18.82±0.93)mU/L与(10.33±0.67)mU/L,t=26.751,P<0.05;(5.13±0.92)与(2.60±0.66),t=8.052,P<0.05]。6周时SGA组内脏脂肪组织中TNF-α、IL-6水平明显高于对照组(t=2.092,P<0.05;t=3.816,P<0.05)。相关性分析显示SGA组仔鼠HOMA-IR与内脏脂肪组织中TNF-α、IL-6、IL-1β水平均呈正相关(r=0.836,P<0.05;r=0.585,P<0.05;r=0.460,P<0.05)。结论有追赶生长的SGA大鼠生命早期发生胰岛素抵抗,可能与内脏脂肪组织中的炎症反应有关。

Objective To investigate the levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),interleukin-1β(IL-1β)and the relationships with insulin resistance(IR)in the rats born small for gestational age(SGA)with catch-up growth.Methods SGA rat model was established by dietary restriction of pregnant rats,the weights of neonatal rats in SGA group and control group were detected weekly.Fasting plasma glucose(FPG)and serum insulin(FINS)levels were measured at 6 weeks after birth in SGA group and control group.HOMA-IR was calculated.The levels of TNF-α,IL-6,and IL-1βin serum and visceral adipose tissue were analyzed by ELISA.Results Mean birth weight of neonatal rats in SGA group was(5.11±0.26)g,which was significantly lower than that of normal group[(6.98±0.62)g](t=-15.066,P<0.05).On the third week,the average body weight in SGA group reached that in control group,achieving catch-up growth.On the 6th week,mean birth weight in SGA group was significantly higher than that of normal group[(229.71±24.41)g and(209.89±27.35)g](t=2.662,P<0.05).The levels of FINS and HOMA-IR in SGA group were significantly higher than those in control group[(18.82±0.93)mU/L and(10.33±0.67)mU/L,t=26.751,P<0.05;(5.13±0.92)and(2.60±0.66),t=8.052,P<0.05].The levels of TNF-αand IL-6 in visceral adipose tissue in SGA group were significantly higher than those in control group(t=2.092,P<0.05;t=3.816,P<0.05).Correlation analysis showed that HOMA-IR was positive correlated with TNF-α,IL-6,and IL-1βin visceral adipose tissue of neonatal rats in SGA group,respectively(r=0.836,P<0.05;r=0.585,P<0.05;r=0.460,P<0.05).Conclusion SGA rats with catch-up growth became IR in their early period,which may be associated with inflammation in visceral adipose tissue.