Mechanisms of Ischemia Reperfusion Injury in Microperfused Afferent Arterioles.

缺血再灌注损伤是休克、移植等缺血性疾病中最重要的病理生理现象之一。为探讨微血管缺血再灌注损伤的机制，在家兔肾皮质浅部，经15分钟缺血再灌注30分钟后，显微解剖出完整的家兔肾传入小动脉（Af-Art），并在60 mmHg下离体灌注。本文观察了去甲肾上腺素（NE）的缩血管作用和乙酰胆碱（Ach）或尼卡地平（Nic）的扩血管作用。在阻断肾动脉前15分钟静脉注射尼克酰胺1 mg/kg/min。缺血再灌注可明显抑制10 μ M Ach引起的血管扩张<-5>（4.7%，n = 5），而对照组仅为5.4%。然而，对5 × 10 μ M NE的反应<-7>保持不变（4.6%（n=4）VS对照组（n=8）中的6.5%），10 μ M Nic诱导的扩张也<-7>保持不变（6.5%（n=7）VS对照组（n=7）中的6.5%）。电镜下可见内皮细胞轻度损伤。仅缺血20分钟后，无论是功能还是组织学上，Af-Arts均无损伤。Nic预处理可逆转缺血再灌注损伤引起的内皮损伤，提示缺血再灌注可引起Af-Art功能和组织学损伤，微血管内皮细胞比平滑肌细胞更易受缺血再灌注损伤。钙拮抗剂通过钙通道依赖性机制改善缺血再灌注损伤的内皮细胞损伤。

Ischemia reperfusion injury is one of the most important pathophysiological phenomena, which occurs in shock, transplants and other ischemic disease. This study was carried out to determine the mechanisms of ischemia reperfusion injury in microvessels.After 15-minute ischemia and 30-minute reperfusion, rabbit afferent arterioles (Af-Art) with the glomerulus intact were microdissected from the superficial cortex of the rabbit kidney and perfused in vitro at 60mmHg. Vasoconstrictor action of norepinephirine (NE) and vasodilator action of acetylcholin (Ach) or nicardipine (Nic) were examined. Af-Art were examined with an electron microscope.Nic 1mg/kg/min was addminstrated intravenously 15 minute before the occulusion of renal artery. Then same protocol was repeated again.The ischemia reperfusion significantly attenuated the dilation induced by 10^<-5>M Ach 4.7% (n=5) VS 5.4% in controls (n=5)}. However, the response to 5x10^<-7>M NE remained unchanged 4.6% (n=4) VS 6.5% in controls (n=8)}, as did the dilation induced by 10^<-7>M Nic 6.5% (n=7) VS 6.5% in controls (n=7)}. Slight damages were observed in the endothelial cells on electron microscopy. There was no damage to Af-Arts after 20 minutes ischemia only, either functionally or histologically. Pretreatment of Nic could reverse endothelial damage by ischemia reperfusion injury.We conclude that short period of the ischema reparfusion could induce functional and histological damage to Af-Art. The endothelial cells of microvessels are more susceptible to ischemia reperfusion than smooth muscle cells. Calcium antagonist improve the endothelial damage by ischemia reperfusion injury via calcium channel dependent mechanisms.