Functional magnetic resonance imaging and immunohistochemical study of hypothalamic function following oral glucose ingestion in rats
Functional magnetic resonance imaging and immunohistochemical study of hypothalamic function following oral glucose ingestion in rats
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DOI：
10.1097/00029330-200707020-00005
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发表时间：
2007-07-20
影响因子：
6.1
通讯作者：
Li Guo-zhen
中科院分区：
文献类型：
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作者：
Min, Chen;Zhang Tie-mei;Li Guo-zhen
研究背景下丘脑通过感受代谢需求和释放调节性神经递质，在代谢调节中起着重要作用。本研究采用血氧水平依赖性功能磁共振成像技术研究了大鼠下丘脑对葡萄糖摄入的反应方法采用功能磁共振成像（BOLD-fMRI）和免疫组化技术，对48只健康大鼠口服葡萄糖60 min后下丘脑的信号强度进行了动态监测（14月龄），包括24只正常体重大鼠（体重（365 +/-76.5）g）和24只超重大鼠（体重（714 +/-83.5）g）。然后，12只大鼠（6只正常，6只超重）在另一天摄入等量的不含葡萄糖的水后进行了重复的fMRI扫描。功能磁共振成像与水摄入的程序是相同的葡萄糖摄入。采用时间聚类分析和强度平均法对fMRI数据进行处理。采用免疫组织化学方法检测各组大鼠下丘脑神经肽Y（neuropeptide Y，NPY）和5-羟色胺（5-hydroxytryptamine，5-HT）的表达。结果口服葡萄糖后19.5-25.5 min，所有大鼠下丘脑fMRI信号强度均出现短暂但显著的下降（平均（3.12 ± 0.78）%）。在超重大鼠中，响应于葡萄糖摄入的信号强度的降低比在正常体重大鼠中观察到的更明显地减弱（（2.2 ± 1.5）% vs（4.2 ± 0.7）%抑制，t=2.12，P < 0.05）。饮水后下丘脑无明显反应。肥胖组大鼠海马神经肽Y阳性细胞百分率略低于对照组（21%vs23%，t=0.71，P > 0.05），但两组间差异无统计学意义;肥胖组5-HT阳性细胞百分率明显低于对照组结论葡萄糖摄入后，下丘脑BOLD信号强度有短暂但显著的降低，与正常人相似。超重和正常体重大鼠下丘脑对葡萄糖摄入的反应不同。肥胖大鼠海马神经肽Y阳性细胞百分率低于对照组，但差异无统计学意义。肥胖组5-HT阳性细胞百分率明显低于对照组。
Background The hypothalamus plays a central role in the regulation of metabolism by sensing metabolic demands and releasing regulatory neurotransmitters. This study investigated the response of the hypothalamus to glucose ingestion in rats by blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) and immunohistochemical techniques to determine the role of the hypothalamus in glycoregulation during disturbances in carbohydrate metabolism.Methods The signal intensity of the hypothalamus was monitored by fMRI for 60 minutes after oral glucose intake in 48 healthy rats (age 14 months), which included 24 normal weight rats (weighing (365 +/- 76.5) g) and 24 overweight rats (weighing (714 +/- 83.5) g). Then, 12 rats (6 normal, 6 overweight) underwent a repeat fMRI scan after consuming an equivalent amount of water without glucose on a separate day. The procedure for fMRI with water intake was the same as for glucose ingestion. fMRI data was processed using time cluster analysis and intensity averaging method. After fMRI, the expression of neuropeptide Y (NPY) and 5-hydroxytryptamine (5-HT) in the hypothalamus of all rats was determined by immunohistochemistry. Positive cells for NPY or 5-HT were counted.Results There was a transient, but significant, decrease in fMRI signal intensity in all rats (mean (3.12 +/- 0.78)%) in the hypothalamus within 19.5-25.5 minutes of oral glucose ingestion. In overweight rats, the decrease in signal intensity in response to the glucose ingestion was more markedly attenuated than that observed in normal weight rats ((2.2 +/- 1.5)% vs (4.2 +/- 0.7)% inhibition, t=2.12, P < 0.05). There was no significant response in the hypothalamus after oral water ingestion. The percentage of NPY positive cells in obese rats were slightly lower than those in control group (21 % vs 23%, t=0.71, P > 0.05); but there was no significant difference between the two groups; the percentage of 5-HT positive cells in obese rats were significantly lower than those in the control group (22% vs 31 %, t=3.25, P < 0.01).Conclusions There is a transient, but significant, decrease in BOLD signal intensity in the hypothalamus following glucose ingestion, which is similar to that observed in humans. The response of the hypothalamus to glucose ingestion was different in overweight and normal weight rats. The percentage of NPY positive cells in obese rats were lower than those in the control group, although this difference was not statistically significant. The percentage of 5-HT positive cells in obese rats was significantly lower than those in the control group.