过氧化物酶增殖体激活受体γ辅助激活因子1 mRNA在OLETF大鼠组织表达的变化

首都医科大学学报 ›› 2010, Vol. 31 ›› Issue (5): 623-627.

过氧化物酶增殖体激活受体γ辅助激活因子1 mRNA在OLETF大鼠组织表达的变化

伍一鸣, 陈程, 张俊清^*

北京大学第一医院内分泌科

收稿日期:1900-01-01 修回日期:1900-01-01 出版日期:2010-10-21 发布日期:2010-10-21
通讯作者: 张俊清

Changes in mRNA Expression of Peroxisome Proliferator-activated Receptor-γ Co-activator 1(PGC-1α) in Different Tissues of OLETF Rats

WU Yi-ming, CHEN Cheng, ZHANG Jun-qing^*

Department of Endocrinology, Peking University First Hospital

Received:1900-01-01 Revised:1900-01-01 Online:2010-10-21 Published:2010-10-21
Contact: ZHANG Jun-qing

摘要/Abstract

摘要：

目的过氧化物酶增殖体激活受体-γ辅助激活因子1（peroxisome proliferator-activated receptor-γ co-activator 1，PGC-1α）是一种重要的核受体辅助激活因子，参与调节肝糖分解、糖异生以及周围组织对葡萄糖的利用，在维持机体能量代谢平衡和糖脂代谢中起重要作用。本研究通过观察PGC-1α mRNA在OLETF大鼠肝脏、骨骼肌、脂肪和胰腺组织中表达的变化，初步探讨PGC-1α在胰岛素抵抗及糖尿病发病中的作用。方法 ① 实验动物模型建立：从第8周开始喂养OLETF和LETO大鼠10％蔗糖水，每周测体质量，于第14、18、22、28周时进行OGTT并测定大鼠血脂值。OLETF大鼠在第18周时全部成为糖尿病大鼠，动物模型建立成功。② 第8周和28周分别取LETO和OLETF大鼠肝脏、骨骼肌、脂肪和胰腺组织，提取总RNA，应用实时定量PCR方法分析组织中PGC-1α mRNA的表达量。结果 ① OLETF大鼠体质量和三酰甘油（triglyceride，TG）随周龄增加逐渐增加，从14周起高于同周龄LETO大鼠，差异均有统计学意义；空腹和糖负荷后胰岛素浓度从22周起OLETF大鼠高于同周龄LETO大鼠。② 第8周时，OLETF大鼠肝脏、骨骼肌、脂肪和胰腺组织PGC-1α mRNA的表达与LETO大鼠比较差异无统计学意义。③ 第28周时，与LETO大鼠相比，OLETF大鼠PGC1α mRNA在肝脏（0.040±0.006 vs 0.074±0.003，P=0.029）和胰腺（0.659±0.299 vs 1.610±0.091，P=0.029）中表达明显下降，而在骨骼肌（0.192±0.065 vs 0.104±0.012，P=0.029）中表达则明显增加。在脂肪组织（0.055±0.036 vs 0.161±0.124，P=0.100）中表达有下降趋势，差异无统计学意义。结论 OLETF大鼠28周时表现出2型糖尿病早期胰岛素抵抗和高血糖的病理变化，PGC-1α mRNA在肝脏、胰腺和脂肪组织表达减少，骨骼肌组织表达增加，可能是2型糖尿病早期胰岛素抵抗和高血糖状态下的一种代偿性反应，提示PGC-1α mRNA在组织内表达变化可能与胰岛素抵抗和2型糖尿病密切相关。

关键词: 过氧化物酶增殖体激活受体 &gamma, 辅助激活因子1, 2型糖尿病, 胰岛素抵抗, OLETF大鼠

Abstract:

Objective Peroxisome proliferator-activated receptor-γ co-activator 1(PGC-1α) is an important nuclear receptor co-activator, which was involved in regulating glycogenolysis, gluconeogenesis and the glucose utilization of the surrounding tissue. It also plays an important role in maintaining the balance of body energy metabolism, glucose and lipid metabolism. Our study was designed to explore the role of PGC-1α in the diabetes and insulin resistance by observing the changes of the PGC-1α mRNA in the liver, skeletal muscle, fat and pancreatic tissues of OLETF rats. Methods ① OLETF and LETO rats were fed with high sugar(10%) at the 8th week, and OLETF rats all became diabeties in the 18th week. ② Four rats of each group were sacrificed in the 8th and 28th week. Liver, skeletal muscle, fat and pancreatic tissues were collected and total RNA were extracted. PGC-1α mRNA expressions was analyzed by using real-time quantitative PCR. Results ① Body weight and TG level of OLETF rats increased with weeks of age dependent and were significant higher than those of same age of LETO rats from 14th week. After fasting and glucose loading, insulin levels of OLETF rats were also significant higher than that of the same age of LETO rats starting from 22nd week. ② At the 8th week, there were no significant difference in PGC-1αmRNA expression between OLETF and LETO rats in the liver, skeletal muscle, fat and pancreatic tissue. ③ At the 28th week, compared with the LETO rats, the PGC-1αmRNA expression of OLETF rats decreased significantly in the liver(0.040±0.006 vs 0.074±0.003, P=0.029) and pancreas(0.659±0.299 vs 1.610±0.091, P=0.029), but increased significantly in skeletal muscle tissues(0.192±0.065 vs 0.104±0.012, P=0.029). It also showed a downward trend in the adipose tissue(0.055±0.036 vs 0.161±0.124, P=0.100).
Conclusion OLETF rat showed insulin resistance and hyperglycemia, a typical pathological feature of early stage of type 2 diabetes at 28th week. The changes of PGC-1α mRNA expression in the liver, skeletal muscle, fat and pancreas of OLETF rat might be a compensatory response in the insulin resistance and hyperglycemia state of early stage of diabetes. It suggested that the changes of PGC-1α expression in the different tissues may be involved in the pathogenesis of insulin resistance and diabetes.

Key words: peroxisome proliferatoractivated receptor&gamma, co-activator 1;type 2 diabetes;insulin resistance;OLETF rat

中图分类号:

R 587.1

伍一鸣;陈程;张俊清. 过氧化物酶增殖体激活受体γ辅助激活因子1 mRNA在OLETF大鼠组织表达的变化[J]. 首都医科大学学报, 2010, 31(5): 623-627.

WU Yi-ming;CHEN Cheng;ZHANG Jun-qing. Changes in mRNA Expression of Peroxisome Proliferator-activated Receptor-γ Co-activator 1(PGC-1α) in Different Tissues of OLETF Rats[J]. Journal of Capital Medical University, 2010, 31(5): 623-627.

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