THE FIBRIN-DERIVED PEPTIDE Bβ15-42 ATTENUATES LIVER DAMAGE IN A RAT MODEL OF LIVER ISCHEMIA/REPERFUSION INJURY
THE FIBRIN-DERIVED PEPTIDE Bβ15-42 ATTENUATES LIVER DAMAGE IN A RAT MODEL OF LIVER ISCHEMIA/REPERFUSION INJURY
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DOI：
10.1097/shk.0b013e31828c2b75
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发表时间：
2013-04-01
期刊：
影响因子：
3.1
通讯作者：
Dahmen, Uta
中科院分区：
文献类型：
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作者：
Liu, Anding;Fang, Haoshu;Dahmen, Uta
肝缺血/再灌注（I/R）后的炎症反应会增加肝手术后肝功能衰竭的风险。旨在预防炎症的策略可能有助于减少肝I/R损伤。最近的研究表明，肽B β 15-42能够通过抑制白细胞迁移和保护内皮屏障功能来减少心脏和肾脏的I/R损伤。根据这些结果，我们假设B β 15-42也可能具有抗炎能力，以保护或减少肝脏I/R损伤。因此，在本研究中，我们旨在评估B β 15-42在大鼠肝脏I/R损伤模型中的作用。大鼠在再灌注开始和2 h后给予B β 15-42。再灌注后0.5、6、24、48 h处死大鼠。I/R后肝脏纤维蛋白原α (Fg α)、Fg β、Fg γ mRNA水平显著升高。通过降低血清转氨酶水平和减少I/R相关的组织病理学改变，fg来源的B β 15-42治疗改善了肝脏I/R损伤。B β 15-42治疗降低了白细胞浸润和肝脏炎症因子的表达。此外，B β 15-42显著降低了高迁移率组盒1的释放，改变了丝裂原活化蛋白激酶的活化。综上所述，B β 15-42处理对肝脏热I/R损伤具有保护作用。B β 15-42的保护作用机制似乎涉及其通过阻止高迁移率的group box 1释放和改变丝裂原激活的蛋白激酶激活来减少肝脏炎症反应的能力。
The inflammatory response after liver ischemia/reperfusion (I/R) contributes to increased risk of liver failure after liver surgery. Strategies aimed to preventing inflammation could be beneficial in reducing liver I/R injury. Recent studies have demonstrated that peptide B beta 15-42 is able to decrease the injury of I/R in heart and kidney by inhibition of leukocyte migration and preserving endothelial barrier function. Prompted by these results, we hypothesized that B beta 15-42 could also possess anti-inflammatory abilities to protect from or reduce hepatic I/R injury. Therefore, in this study, we aimed to evaluate the effects of B beta 15-42 in a model of liver I/R injury in rats. Rats were treated with B beta 15-42 at initiation of reperfusion and 2 h thereafter. Rats were killed at 0.5, 6, 24, and 48 h after reperfusion. Hepatic mRNA levels of fibrinogen-alpha (Fg alpha), Fg beta, Fg gamma were significantly increased after I/R. Treatment with Fg-derived B beta 15-42 ameliorated liver I/R injury, as indicated by lower serum aminotransferase levels and fewer I/R-associated histopathologic changes. B beta 15-42 treatment decreased leukocyte infiltration and expression of hepatic inflammatory cytokines. Moreover, B beta 15-42 significantly reduced high-mobility group box 1 release and altered mitogen-activated protein kinase activation. In conclusion, B beta 15-42 treatment protected against liver warm I/R injury. The mechanism of protective action of B beta 15-42 seemed to involve its ability to reduce hepatic inflammatory response through preventing high-mobility group box 1 release and altering mitogen-activated protein kinase activation.