摘要
目的 基于LXR-α/SREBP-1c信号通路探讨生命幼年期营养不良对生命成年期影响的临床意义.方法 3周龄雄性大鼠32只,随机分为普食组(A组)、饥饿普食组(B组)、高脂组(C组)和饥饿高脂组(D组)四组.在观察0周和9周测定空腹血糖和甘油三酯、胰岛素抵抗指数(HOMA-IR)、肝脏的病理改变.用RT-PCR方法检测肝脏组织的肝X受体α(LXR-α)、固醇调节元件结合蛋白-1c(SREBP-1c)、脂肪酸合成酶(FAS)、硬脂酰辅酶A去饱和酶1(SCD1)、过氧化物酶体增殖物激活受体-α(PPAR-α)的mRNA基因表达.结果 A、B、C 和 D 组在饮食喂养 9 周时胰岛素分别为(13.72±0.84)、(13.93±1.51)、(28.89±3.14)和(32.41±2.25)ng/ml,C、D组分别高于A、B组,差异有统计学意义(P＜0.05).A、B、C、D组实验结束时HOMA-IR分别为(2.91±0.32)、(3.08±0.40)、(6.38±0.26)和(7.39±0.48).C、D 组分别 高于 A、B 组,差异有统计学意义(P＜0.05).D 组大鼠肝细胞含脂滴空泡,小叶中央区和周边区受累均明显.B组和C组也有的脂肪变性较轻.C组和D组肝脏中LXR-α、SREBP-1c、FAS、SCD1 mRNA基因表达水平均显著高于A、B组,差异有统计学意义(P＜0.05).结论 经受"二次打击"的大鼠,可能导致生命成年期的脂质的合成增强,进而出现代谢性异常.
Abstract
Objective To explore the clinical significance of malnutrition in infancy of life on adult life based on LXR-α/SREBP-1c signaling pathway.Methods A total of 32 3-week-old male rats were randomly divided into four groups:the general diet group(group A),the hunger-general diet group(group B),the high-fat group(group C)and the hunger-high-fat group(group D).Fasting blood glucose,triglyceride,homeostasis model assessment of insulin resistance(HOMA-IR)and pathological changes of liver were measured after 0 and 9 weeks of observation.The mRNA expression of liver X receptor-α(LXR-α),sterol Regulatory element binding protein-1c(SREBP-1c),fatty acid synthase(FAS),stearoyl-CoA desaturase 1(SCD1)and peroxisome proliferator-activated receptor-α(PPAR-α)in liver tissue was detected by RT-PCR.Results The insulin levels in groups A,B,C and D were(13.72±0.84),(13.93±1.51),(28.89±3.14)and(32.41±2.25)ng/ml respectively after 9 weeks of dietary feeding,and the insulin levels in groups C and D were higher than those in groups A and B respectively,with statistically significant differences(P＜0.05).At the end of the experiment,the HOMA-IR of groups A,B,C and D were(2.91±0.32),(3.08±0.40),(6.38±0.26)and(7.39±0.48)respectively.Groups C and D were higher than Groups A and B respectively,with statistically significant differences(P＜0.05).In group D,there were lipid-containing vacuoles in hepatocytes,and the central and peripheral areas of lobules were obviously involved.Some rats in groups B and C had mild steatosis.The mRNA expression levels of LXR-α,SREBP-1c,FAS and SCD1 mRNA in the liver of rats in groups C and D were significantly higher than those in groups A and B,with statistically significant differences(P＜0.05).Conclusion The"secondary attack"to rats may lead to the enhancement of lipid synthesis in adult life,which may lead to metabolic abnormalities.
基金项目
上海市黄浦区科研项目(面上)(HLM202009)
维普
万方数据