Ibayashi S, Nagao T, Kitazono T, Ooboshi H, Kitayama J, Sadoshima S, Fujishima M
Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Neurochem Res. 2000 Mar;25(3):349-55. doi: 10.1023/a:1007536919827.
The present study was designed to examine the effect of a calcium antagonist isradipine (PN200-110: PN) on local cerebral blood flow and brain tissue metabolism after 1-hour supratentorial ischemia induced by bilateral carotid artery ligation (BCL) in spontaneously hypertensive rats (SHR). PN, dissolved in ethanol plus polyethylene glycol 400, diluted with saline to make the final concentration of 0.25mg/ml and 2.5mg/ml, was administered subcutaneously either 30 min prior to BCL or just after the induction of incomplete cerebral ischemia (n = 7 in each group). Vehicle injection was served as a control group (n = 7). Cerebral blood flow in the parietal cortex (CBF) and the cerebellar cortex (CeBF) was measured by hydrogen clearance technique, and the supra- and infratentorial metabolites of the brain frozen in situ were determined by the enzymatic method. Blood pressure was lowered, but CBF was increased by PN administration in pre-BCL treatment study. After 1 hour of BCL, CBF decreased to around 10% or less of the resting value, being insignificant among the groups. Brain adenosine triphosphate was better preserved in PN-administered groups. The increase in lactate level tended to reduce dose dependently by PN treatment. PN also reduced the metabolic alterations in brain tissue with significance, even when administered just after the induction of forebrain ischemia. It is considered that pre- as well as post-BCL administration of PN is beneficial to attenuate the metabolic alterations in incomplete forebrain ischemia in SHR.
本研究旨在探讨钙拮抗剂伊拉地平（PN200 - 110：PN）对自发性高血压大鼠（SHR）双侧颈动脉结扎（BCL）诱导的1小时幕上缺血后局部脑血流量和脑组织代谢的影响。将PN溶解于乙醇加聚乙二醇400中，用生理盐水稀释至最终浓度为0.25mg/ml和2.5mg/ml，在BCL前30分钟或不完全脑缺血诱导后立即皮下给药（每组n = 7）。注射溶媒作为对照组（n = 7）。采用氢清除技术测量顶叶皮质（CBF）和小脑皮质（CeBF）的脑血流量，并用酶法测定原位冷冻脑的幕上和幕下代谢产物。在BCL前治疗研究中，PN给药可降低血压，但增加脑血流量。BCL 1小时后，脑血流量降至静息值的10%左右或更低，各组间无显著差异。PN给药组脑三磷酸腺苷保存较好。PN治疗使乳酸水平升高趋势呈剂量依赖性降低。即使在前脑缺血诱导后立即给药，PN也能显著减轻脑组织的代谢改变。认为BCL前后给予PN均有利于减轻SHR不完全前脑缺血中的代谢改变。
