Potentiated hepatic microcirculatory response to endothelin-1 during polymicrobial sepsis
Potentiated hepatic microcirculatory response to endothelin-1 during polymicrobial sepsis
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DOI：
10.1097/00024382-200211000-00005
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发表时间：
2002-11-01
期刊：
影响因子：
3.1
通讯作者：
Clemens, MG
中科院分区：
文献类型：
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作者：
Baveja, R;Kresge, N;Clemens, MG
我们进行了这项研究，以阐明内皮素（ET-1）在介导的肝微循环功能障碍的反应，脓毒症。盲肠结扎和穿刺（CLP）24小时后，我们进行活体显微镜在体内和离体灌注肝脏。门静脉阻力增加响应ET-1在假和脓毒症大鼠，两者之间没有显着差异，无论是在体内或在离体肝脏。正弦体积流量（Q.）采用红细胞速度（V-RBC）和血窦直径（D.）以确定微血管血流动力学的完整性。Q.在体内和离体肝脏中，与假手术组相比，CLP大鼠肝脏对ET-1的反应性降低（P < 0.05，CLP vs. sham）。CLP组大鼠肝窦内注射ET-1后，与假手术组相比，窦壁收缩程度更明显（P < 0.05），窦壁阻力也更大。微血管高反应性伴随着肝细胞损伤在CLP大鼠，但不是在假手术大鼠。RT-PCR检测ET-1及其受体ETA和ET.诱导型和组成型一氧化氮（NO）合酶（分别为iNOS和eNOS）和血红素加氧酶1（HO-1）。CLP后ET-1和ETB mRNA均升高，而ETA mRNA有下降趋势，但无统计学意义。CLP大鼠肝脏eNOS mRNA水平无显著变化，但NOS表达显著增加（是假手术组的13.5倍）。假手术组和CLP组HO-1 mRNA水平无明显变化。综上所述，这些结果表明，脓毒症敏感的肝微循环ET-1。更重要的是，脓毒症中ET-1导致的微循环血流受损有助于肝损伤。此外，内皮素和NO之间的局部失衡可能介导脓毒症期间微血管反应的改变。
We conducted this study to elucidate the role of endothelins (ET-1) in mediating the hepatic microcirculatory dysfunction observed in response to sepsis. Following 24 h of cecal ligation and puncture (CLP), we performed intravital microscopy both in vivo and on isolated perfused livers. Portal resistance increased in response to ET-1 in both sham and septic rats, with no significant difference between the two in either in vivo or in isolated livers. Sinusoidal volumetric flow (Q.) was evaluated using red blood cell velocity (V-RBC) and sinusoidal diameter (D.) to determine microvascular hemodynamic integrity. Q. decreased in response to ET-1 in livers from CLP rats compared with sham (P < 0.05, CLP vs. sham) in both in vivo and isolated livers. In vivo infusion of ET-1 resulted in greater constriction of sinusoids in the CLP group compared with sham (P < 0.05), resulting in higher sinusoidal resistance. Microvascular hyper-responsiveness was accompanied by hepatocellular injury in CLP rats, but not in sham rats. RT-PCR was performed to measure mRNA levels of ET-1, its receptors ETA and ET., inducible and constitutive nitric oxide (NO) synthase (iNOS and eNOS, respectively), and heme oxygenase 1 (HO-1). After CLP, both ET-1 and ETB mRNA increased, whereas ETA mRNA tended to decrease, although the change was not statistically significant. Livers from CLP rats showed no significant change in levels of eNOS mRNA, but showed a significant increase in NOS expression (13.5-fold over sham). There was no change in the level of HO-1 mRNA between sham and CLP groups. Taken together, these results suggest that sepsis sensitizes the hepatic microcirculation to ET-1. More importantly, an impaired microcirculatory flow due to ET-1 in sepsis contributes to hepatic injury. Further, localized imbalances between endothelins and NO may mediate the altered microvascular response during sepsis.