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Studies on the involvement of intrahypothalamic angiotensin type 2 receptors in the development of fever in rats

下丘脑内血管紧张素2型受体参与大鼠发热发生的研究

基本信息

批准号：
13470012
负责人：
WATANABE Tatsuo
金额：
$ 9.41万
依托单位：
Tottori University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470012/
关键词：
Angiotensin II AT2receptor Fever Hypothalamus Immunohistochemistry LPS Rat プロスタグランディンE

项目摘要

We have recently found that angiotensin II (ANG II) type 2 receptors within the hypothalamus (preoptic and anterior hypothalamic region) play an important role in the fever induced by intrahypothalamic injection of prostaglandin E2. However, it is still unknown how ANG II and type 2 receptors contribute to the development of the fever. We speculated that during fever type 2 receptors are induced in the hypothalamus of the rats, leading to fever enhancement. In order to test this possibility, we decided to investigate the induction of the type 2 receptors in the brain of rats made febrile by the injection of pyrogens, using immunohistochemistry technique. At first, we made our own antibody against type 2 receptors for the immunohistochemistry. Actually, we synthesized a C-terminal peptide of the receptor consisting of eleven amino acids and injected this peptide three times to rabbits. Eight weeks after the first injection, the anti-serum was obtained and purified by affinity chromatography. We used this antibody to examine the induction of the receptors in the brain of afebrile and febrile rats. However, the signal of the ANG type 2 receptor was not detected in the hypothalamus of rats which received intraperitoneal (i.p.) injection of either LPS (1mg/kg) or saline. Furthermore, rats given intracerebroventricular injection of LPS (2μg) did not show any receptor signals in the hypothalamus. These results do not support the hypothesis that type 2 receptors are induced in the hypothalamus during fever. However, we will continue to examine the possibility (hypothesis) described above using more sophisticated techniques with high sensitivity.

我们最近发现，血管紧张素II（ANG II）2型受体在下丘脑（视前区和下丘脑前区）下丘脑内注射前列腺素E2引起的发热中起重要作用。然而，它仍然是未知的血管紧张素II和2型受体如何有助于发热的发展。我们推测，在发热期间，2型受体在大鼠的下丘脑中被诱导，导致发热增强。为了测试这种可能性，我们决定研究2型受体的诱导，在大鼠的大脑中的发热注射热原，使用免疫组织化学技术。首先，我们自己制备了抗2型受体的抗体用于免疫组织化学。实际上，我们合成了一个由11个氨基酸组成的受体的C-末端肽，并将此肽注射给兔子三次。第一次注射后8周，获得抗血清并通过亲和层析纯化。我们使用这种抗体来检查在无发热和发热大鼠的脑中的受体的诱导。然而，在腹腔注射（i. p.）注射LPS（1 mg/kg）或生理盐水。此外，侧脑室注射LPS（2μg）的大鼠在下丘脑中未显示任何受体信号。这些结果不支持发热时下丘脑中2型受体被诱导的假设。然而，我们将继续使用更复杂的高灵敏度技术来验证上述可能性（假设）。