Protective effect of proteinase-activated receptor 2 activation on motility impairment and tissue damage induced by intestinal ischemia/reperfusion in rodents
Protective effect of proteinase-activated receptor 2 activation on motility impairment and tissue damage induced by intestinal ischemia/reperfusion in rodents
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DOI：
10.2353/ajpath.2006.051098
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发表时间：
2006-07-01
影响因子：
6
通讯作者：
Sternini, Catia
中科院分区：
文献类型：
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作者：
Cattaruzza, Fiore;Cenac, Nicolas;Sternini, Catia
我们假设蛋白酶激活受体2（PAR（2））调节缺血/再灌注引起的肠损伤。与假手术组相比，缺血（1小时）+再灌注（6小时）显著延迟胃肠道传输（GIT）。十二指肠内注射PAR（2）激活肽SLIGRL-NH 2显著加速缺血/再灌注大鼠的转运，但在假手术大鼠中没有。与PAR（2）（+/+）SIJGRL-NH 2相比，在缺血/再灌注和假手术PAR（2）（-/-）小鼠中GIT显著延迟。在PAR 2 +/+小鼠中显著加速缺血/再灌注的转运，但在PAR（2）（+/+）小鼠中没有。预防肥大细胞脱颗粒与crologyn，消融内脏传入，辣椒素，降钙素基因相关肽（CGRP）和神经激肽-1受体与CGRP（8-37）和RP 67580的拮抗作用，分别取消SLIGRL-NH 2诱导的刺激作用在缺血/再灌注过境。SLIGRL-NH 2显著降低了组织损伤;在克罗埃因、辣椒素或RP 67580治疗的大鼠中未观察到这种作用，但在CGRP治疗后检测到这种作用（8-37）。SLIGRL-NH 2对肠PARI mRNA表达无明显影响。我们认为PAR 2通过依赖于肥大细胞和内脏传入神经的机制调节肠缺血/再灌注中的GIT和组织损伤。PAR对运输的影响可能是由CGRP和P物质介导的，而对组织损伤的影响似乎涉及P物质而不是CGRP。PAR可能是肠缺血/再灌注神经免疫通讯的信号系统。
We hypothesized that proteinase-activated receptor-2 (PAR(2)) modulates intestinal injuries induced by ischemia/reperfusion. Ischemia (I hour) plus reperfusion (6 hours) significantly delayed gastrointestinal transit (GIT) compared with sham operation. Intraduodenal injection of PAR(2)-activating peptide SLIGRL-NH2 Significantly accelerated transit in ischemia/reperfusion but not in sham-operated rats. GIT was significantly delayed in ischemia/reperfusion and sham-operated PAR(2)(-/-) mice compared with PAR(2)(+/+) SIJGRL-NH2 Significantly accelerated transit in ischemia/reperfusion in PAR2+/+ but not in PAR(2)(+/+) mice. Prevention of mast cell degranulation with cromolyn, ablation of visceral afferents; with capsaicin, and antagonism of calcitonin gene-related peptide (CGRP) and neurokinin-1 receptors with CGRP(8-37) and RP67580, respectively, abolished the SLIGRL-NH2-induced stimulatory effect on transit in ischemia/reperfusion. Tissue damage was significantly reduced by SLIGRL-NH2; this effect was not observed in cromolyn-, capsaicin-, or RP67580-treated rats but was detected following CGRP(8-37). lntestinal PARI mRNA levels were not affected by SLIGRL-NH2 in ischemia/reperfusion. We propose that PAR2 modulates GIT and tissue damage in intestinal ischemia/reperfusion by a mechanism dependent on mast cells and visceral afferents. PAR, effect on transit might be mediated by CGRP and substance P, whereas the effect on tissue damage appears to involve substance P but not CGRP. PAR, might he a signaling system in the neuroimmune communication in intestinal ischemia/reperfusion.