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Research for immunological reaction as a pathogenesis of vasospasm after subarachnoid hemorrhage.

蛛网膜下腔出血后血管痉挛发病机制中免疫反应的研究。

基本信息

批准号：
04670857
负责人：
NISHIZAWA Shigeru
金额：
$ 1.15万
依托单位：
Hamamatsu University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04670857/
关键词：
subarachnoid hemorrhage vasospasm immunosuppressants 脳血管〓縮免疫押制剤

项目摘要

We hypothesized that an immunological reaction plays a role in the development of vasospasm afer subarachnoid hemorrhage (SAH). Under this hypothesis, we had investigated the therapeutic effect of cyclosporine for vasospasm, and obtained a favorable result. To testify this hypothesis further, we used a new potent immunosuppressant, FK-506, for vasospasm. We also examined chronological changes of serum compliments (C_3, CH_<50>). After sacrificing an animal, we checked pharmachological effect of FK-506 on K^+-dependent and protein kinase C (PKC)-dependent contarctions. Furthermore, we investigated immunoglobulin deposition in the arterial wall by immunohistochemistry. Dogs were classified into four groups, sham (saline injected), SAH (two-hemorrhage model), FK-506-treated I (0.15mg/kg i.m.) and-treated II (0.3mg/kg i.m.) groups. Angiograms showed severe vasospasm in SAH,treated I and ll, and no significant difference was observed among these three groups. Serum compliments did not show any significant changes in four guoups. FK-506 did not show any vasodilatory effects on K^+-dependent and PKC-dependent contarctions. Because of technical problems, we did not succeed in staining any immunoglobulin depositions in arterial walls in any group.Contrary to our expectation, FK-506 did not show any therapeutic effect on vasospasm after SAH.There is a significant discepancy between cyclosporine and FK-506 regarding therapeutic effect on vasospasm. We speculated that this difference might be based on the pnarmacological difference of immunosuppression between the two, especially the mechanism of suppression on the production of interleukine 2. If we could have a chance to investigate this point, a pathogenensis of vasospasm could be clarified further.

我们假设免疫反应在蛛网膜下腔出血（SAH）后血管痉挛的发展中起作用。在此假设下，我们研究了环孢素治疗血管痉挛的效果，并取得了良好的结果。为了进一步证实这一假设，我们使用了一种新的有效免疫抑制剂FK-506来治疗血管痉挛。我们还检测了血清补液（C_3, CH_<50>）的时间变化。在动物牺牲后，我们检查了FK-506对K^+依赖性和PKC依赖性收缩的药理学作用。此外，我们用免疫组织化学方法研究了免疫球蛋白在动脉壁的沉积。将狗分为4组，假手术组（注射生理盐水）、SAH组（两次出血模型）、fk -506治疗I组（0.15mg/kg i.m）和II组（0.3mg/kg i.m）。血管造影显示SAH患者，治疗I和治疗ii时血管痉挛严重，三组间无显著差异。血清赞美在四组中没有显示出任何显著的变化。FK-506对K^+依赖性和pkc依赖性收缩没有任何血管扩张作用。由于技术问题，我们没有成功地染色任何组动脉壁的任何免疫球蛋白沉积。与我们的预期相反，FK-506对SAH后血管痉挛没有任何治疗作用。环孢素与FK-506对血管痉挛的治疗效果存在显著差异。我们推测这种差异可能是基于两者免疫抑制的药理学差异，特别是对白细胞介素2产生的抑制机制。如果我们能有机会研究这一点，血管痉挛的病因可能会进一步明确。