Biochemical research for cerebral vasospasm and edema, using cultured arterial smooth muscle cells

脑血管痉挛是蛛网膜下腔出血的主要并发症之一。尽管有大量的实验和临床研究，脑血管痉挛的发病机制尚未明确，其病因是公认的多因素。近年来的研究表明花生四烯酸代谢产物，尤其是前列环素和血栓素a_2在前列腺增生中起重要作用，但有关脂氧合酶产物（白三烯、HETE等）的实验和临床研究较少。报道较少。白三烯C_4、D_4（LTC_4、LTD_4）具有收缩平滑肌和增强血脑屏障通透性的生物活性。本研究采用高效液相色谱法（HPLC）测定了蛛网膜下腔出血（SAH）患者脑脊液（CSF）中LTC_4、LTD_4浓度。8例进行了连续测量。无症状性脑血管痉挛者脑脊液中LTC_4值持续低水平（<2ng/ml），而有症状性脑血管痉挛者则明显升高。(the最大值为18.97ng/ml。在症状性脑血管痉挛发生前，LTC_4水平明显升高。而在症状性脑血管痉挛的脑脊液中仅检测到3例LTD_4。LTD_4浓度较低，水平变化不明显。CSF中LT（尤其是LTC_4）浓度与症状性脑血管痉挛的严重程度密切相关。LTC_4使培养的动脉平滑肌细胞发生一定程度的收缩（细胞面积最大减少35%）。结果提示LTD_4与脑血管痉挛的发生密切相关，而LTD_4与缺血性脑损伤后脑水肿的发生密切相关。

One of the major complications following aneurysmal subarachnoid hemorrhage is the occurrence of cerebral vasospasm. In spite of numerous experimental and clinical studies, the pathogenesis of cerebral vasospasm has not been obvious and its etiology is recognized multifactorial. Recent investigations have suggested the important roles of arachidonic acid metabolites, especially prostacyclin and thromboxane a_2,but expermental and clinical studies concerning lipoxygenase products (Leukotriene, HETE etc.) have been less reported. We are interested in leukotriene C_4, D_4 (LTC_4, LTD_4) which have the biological activity of smooth muscle constriction and of enhancement of blood brain barrier permeability. In this clinical study, LTC_4, LTD_4 concentration in CSF from the patients with aneurysmal SAH were measured, using high performance liquid chromatography (HPLC). Sequential measurement were performed in 8 cases. Values of LTC_4 in the CSF were constantly at low levels (less than 2ng/ml) in cases without symptomatic vasospasm, whereas they were significantly elevated in cases with symptomatic vasospasm. (the maximum 18.97ng/ml). the levels of LTC_4 were remarkably elevated before the onset of symptomatic vasospasm. On the other hand, LTD_4 in the CSF were detected in only 3 cases with symptomatic vasospasm. LTD_4 concentrations were lower and alteration of levels were less remarkable than LTC_4. A close correlation between the severity of symptomatic vasospasm and LT (especially LTC_4) concentraion in the CSF were demonstrated. LTC_4 caused definite contraction of cultured arterial smooth muscle cells (maximum decreased percentage of cell area : 35%). These results appear to indicate that LTC_4 is closely related to the occurrence of cerebral vasospasm, and that LTD_4 to cerebral edema after ischemic brain damage.