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

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，我们研究了环孢素对血管痉挛的治疗作用，并获得了有利的结果。为了进一步证实这一假设，我们使用了一种新的有效的免疫抑制剂FK-506，用于血管痉挛。同时观察血清补体（C_3、CH_2）的时间变化<50>。在处死动物后，我们检测了FK-506对K^+依赖性和蛋白激酶C（PKC）依赖性心肌收缩的药理作用。此外，我们研究免疫球蛋白沉积在动脉壁的免疫组织化学。将犬分为4组，假手术组（注射生理盐水）、SAH组（二次出血模型）、FK-506治疗组（I组，0.15mg/kg，i.m.）处理组II（0.3mg/kg i.m.）组血管造影显示SAH、治疗I组和治疗II组血管痉挛严重，三组间无显著差异。血清补体在四组中无明显变化。FK-506对K^+依赖性和PKC依赖性收缩无舒张作用。由于技术问题，我们未能成功地在任何组的动脉壁中染色任何免疫球蛋白沉积，与我们的预期相反，FK-506对SAH后的血管痉挛没有任何治疗作用，环孢素和FK-506对血管痉挛的治疗作用存在显著差异。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，特别是抑制白细胞介素2产生的机制。如果我们能有机会研究这一点，血管痉挛的发病机制可能会得到进一步澄清。

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.