Zhao Li Ru, Spellman Steve, Kim Jonggul, Duan Wei-Ming, McCarthy James B, Low Walter C
Department of Neurosurgery, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
Brain Res. 2005 Aug 23;1054(1):1-8. doi: 10.1016/j.brainres.2005.04.056.
Leukocytes have been investigated during the past decade for their roles in secondary tissue damage after ischemia/reperfusion injury. Peptide PRARIY, a synthetic fibronectin peptide, has shown an anti-adhesion effect in in vitro studies. Previous studies have demonstrated that anti-adhesion agents lead to reductions in apoptosis. The purpose of the present study was to determine whether the peptide PRARIY displays anti-inflammatory, anti-apoptotic, and neuroprotective effects following transient focal brain ischemia in rats. Twenty-six male Sprague-Dawley rats (300-350 g) were randomly divided into three groups: phosphate-buffered saline (PBS) controls, PRARI controls, and PRARIY treatments. The right middle cerebral artery was transiently occluded using a 4-0 nylon suture. One hour later, the occluder was withdrawn, and reperfusion was maintained for 48 h. Immediately after reperfusion, the peptides (20 mg/kg, dissolved in PBS) and the same volume of PBS were continuously infused through the right external carotid artery using an osmotic minipump for 24 h. Neurological deficits were examined at 3, 24, and 48 h after ischemia. Forty-eight hours after reperfusion, the rats were sacrificed for determining infarction size, leukocyte infiltration, and apoptosis in the ischemia area. Unexpectedly, PRARIY did not influence leukocyte infiltration. However, PRARIY-treated rats showed significantly functional outcome, reduction of infarction size, decrease of TUNEL positive cells, and increase of Bcl-2 (anti-apoptotic protein) positive cells in the ischemic areas when compared to the controls. These data indicate that the peptide PRARIY exerts its neuroprotective effects via supporting neural cell survival rather than anti-leukocyte recruitment following brain ischemia/reperfusion injury.
在过去十年中，人们对白细胞在缺血/再灌注损伤后的继发性组织损伤中的作用进行了研究。肽PRARIY是一种合成的纤连蛋白肽，在体外研究中显示出抗粘附作用。先前的研究表明，抗粘附剂可导致细胞凋亡减少。本研究的目的是确定肽PRARIY在大鼠短暂性局灶性脑缺血后是否具有抗炎、抗凋亡和神经保护作用。26只雄性Sprague-Dawley大鼠（300-350克）被随机分为三组：磷酸盐缓冲盐水（PBS）对照组、PRARI对照组和PRARIY治疗组。使用4-0尼龙缝线短暂阻断右侧大脑中动脉。一小时后，取出阻塞物，并维持再灌注48小时。再灌注后立即使用渗透微型泵通过右侧颈外动脉连续输注肽（20毫克/千克，溶解于PBS）和相同体积的PBS，持续24小时。在缺血后3、24和48小时检查神经功能缺损。再灌注48小时后，处死大鼠以确定梗死面积、白细胞浸润和缺血区域的细胞凋亡情况。出乎意料的是，PRARIY并未影响白细胞浸润。然而，与对照组相比，接受PRARIY治疗的大鼠在缺血区域显示出明显更好的功能结局、梗死面积减小、TUNEL阳性细胞减少以及Bcl-2（抗凋亡蛋白）阳性细胞增加。这些数据表明，肽PRARIY在脑缺血/再灌注损伤后通过支持神经细胞存活而非抗白细胞募集发挥其神经保护作用。
