Armstead W M, Mirro R, Zuckerman S L, Shibata M, Leffler C W
Department of Physiology and Biophysics, University of Tennessee, Memphis 38163.
Am J Physiol. 1993 Feb;264(2 Pt 2):H381-5. doi: 10.1152/ajpheart.1993.264.2.H381.
We observed previously that 20 min of global cerebral ischemia followed by 45 min of reperfusion selectively blocked cerebral vasodilation to hypercapnia and hypotension. This study determines the effects of pretreatment with transforming growth factor-beta (TGF-beta) on cerebrovascular responses after cerebral ischemia in piglets equipped with closed cranial windows. Hypercapnia-induced pial arteriolar dilation was blocked after cerebral ischemia (20 +/- 1 vs. 2 +/- 1% dilation before and after ischemia, respectively). Similarly, the increases in periarachnoid cortical cerebrospinal fluid 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) and prostaglandin E2 (PGE2) concentration in response to hypercapnia were blocked (2.5 +/- 0.2- vs. 0.2 +/- 0.4-fold and 2.1 +/- 0.1- vs. 0.3 +/- 0.4-fold increase in 6-keto-PGF1 alpha and PGE2, respectively). Treatment with topical TGF-beta (400 ng/ml) before and during ischemia-reperfusion attenuated the loss of hypercapnia-induced cerebrovascular dilation (20 +/- 1 vs. 14 +/- 1% dilation before and after ischemia, respectively) and the loss of associated changes in cerebrospinal fluid prostanoids (2.0 +/- 0.2- vs. 1.7 +/- 0.2-fold and 2.3 +/- 0.2- vs. 2.2 +/- 0.3-fold increase in 6-keto-PGF1 alpha and PGE2 before and after ischemia, respectively). The loss of cerebrovascular dilation in response to hemorrhagic hypotension after ischemia was similarly prevented by TGF-beta. Cerebrovascular dilation to topical isoproterenol was unchanged after ischemia. TGF-beta may preserve endothelial cell function. We conclude that topical TGF-beta can attenuate cerebromicrovascular compromise caused by ischemia-reperfusion in newborn pigs.
我们之前观察到，全脑缺血20分钟后再灌注45分钟，会选择性地阻断大脑对高碳酸血症和低血压的血管舒张反应。本研究确定了在装有闭合式颅窗的仔猪脑缺血后，用转化生长因子-β（TGF-β）预处理对脑血管反应的影响。脑缺血后，高碳酸血症引起的软脑膜小动脉扩张受到阻断（缺血前后的扩张分别为20±1%和2±1%）。同样，蛛网膜下皮质脑脊液中6-酮前列腺素F1α（6-keto-PGF1α）和前列腺素E2（PGE2）浓度因高碳酸血症而增加的情况也受到阻断（6-keto-PGF1α和PGE2分别从2.5±0.2倍增加至0.2±0.4倍以及从2.1±0.1倍增加至0.3±0.4倍）。在缺血-再灌注之前和期间用局部TGF-β（400 ng/ml）处理，可减轻高碳酸血症引起的脑血管扩张的丧失（缺血前后的扩张分别为20±1%和14±1%）以及脑脊液前列腺素相关变化的丧失（缺血前后6-keto-PGF1α和PGE2分别从2.0±0.2倍增加至1.7±0.2倍以及从2.3±0.2倍增加至2.2±0.3倍）。缺血后因出血性低血压导致的脑血管扩张丧失同样可被TGF-β预防。缺血后对局部异丙肾上腺素的脑血管扩张反应未发生改变。TGF-β可能会保留内皮细胞功能。我们得出结论，局部TGF-β可减轻新生猪缺血-再灌注引起的脑微血管损伤。
