异氟醚及乳化异氟醚的抗炎及肝肺保护作用研究
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摘要
肝脏缺血再灌注损伤是肝脏外科常见的问题,而肝脏功能的受损常常造成内毒素血症,反过来又可造成肝脏功能受损的加重,因此,肝脏缺血再灌注损伤和内毒素被认为是影响围术期肝脏功能的两大主要致病因素。近年来研究显示以异氟醚为代表的吸入麻醉药可明显减轻脏器的缺血再灌注及内毒素性损伤,但在肝脏保护方面尚不清楚,本课题通过建立单纯肝脏缺血再灌注模型和再灌注期复合内毒素腹腔给药的肝脏损伤模型,对异氟醚及其新型静脉制剂-乳化异氟醚的抗炎及脏器保护作用及相关机制进行了初步研究,并采用特异性蛋白活性阻断剂及诱导剂等工具药对HO-1的肝脏保护作用,及HO-1在异氟醚肝脏保护机制中的作用进行了初步研究。主要结论有:异氟醚预处理可减轻大鼠肝脏缺血再灌注损伤及缺血再灌注复合内毒素性肝脏损伤,抑制促炎细胞因子释放,减少中性粒细胞在肝组织的浸润,保护肝脏;再灌注期复合内毒素腹腔注射可明显加重大鼠肝脏缺血再灌注损伤和炎症细胞因子反应;诱导上调肝脏HO-1的表达及HO-1活性的增强可抑制大鼠肝脏缺血再灌注损伤介导的促炎细胞因子释放,减少中性粒细胞在肝组织的浸润,减轻肝脏损伤;异氟醚预处理的肝脏保护作用与其上调肝脏缺血再灌注损伤后肝脏内源性保护蛋白HO-1的表达及活性有关;乳化异氟醚预处理可明显减轻大鼠肝脏缺血再灌注损伤介导的急性肺损伤,其机制可能与其抑制NFκB的激活,减少促炎细胞因子TNFα的释放,抑制ICAM-1表达,减少中性粒细胞在肺组织的浸润有关。
Hepatic ischemia followed by reperfusion is a major clinical problem occurring during transplantation, liver resection , shock, and so on. And the failure of liver often induced endotoxin translocation and endotoxemia, which aggravate live injuy. Therefore, hepatic ischemia-reperfusion and endotoxemia are considered to be the two key factors associated with perioperative liver injury.Recent studies suggest that volatile anesthetics isoflurane pretreatment is able to inhibit inflammatory reaction and reduce ischemia-reperfusion(I/R) injury. In our study, we investigate the effect of isoflurane pretreatment on inflammation reaction and hepatic Ischemia-Reperfusion injury combined with or without lipopolysaccharide in rats,and investigate the emulsified isoflurane pretreatment on the inflammation reaction and lung injury induced by hepatic I/R in rats. A model of segmental hepatic ischemia-Reperfusion injury combined with or without lipopolysaccharide in rats were used in our study. The HO-1 inducer and inhibitor were used to investigate the role of HO-1 in the mechanism of protective effect of isoflurane.The follows are the main conclusions: Isoflurane pretreatment might reduce the inflammation reaction and live injury induced by hepatic ischemia-reperfusion combined with or without lipopolysaccharide in rats ; Isoflurane pretreatment might increase the HO-1 expression in live tissue hepatic ischemia-reperfusion , and which reduce inflammation reaction and liver injury;Ischemia-reperfusion in liver induced evident inflammation reaction and lung injury in rats, which were significantly attenuated by emulsified isoflurane pretreatment.
Hepatic ischemia followed by reperfusion is a major clinical problem occurring during transplantation, liver resection , shock, and so on. And the failure of liver often induced endotoxin translocation and endotoxemia, which aggravate live injuy. Therefore, hepatic ischemia-reperfusion and endotoxemia are considered to be the two key factors associated with perioperative liver injury.Recent studies suggest that volatile anesthetics isoflurane pretreatment is able to inhibit inflammatory reaction and reduce ischemia-reperfusion(I/R) injury. In our study, we investigate the effect of isoflurane pretreatment on inflammation reaction and hepatic Ischemia-Reperfusion injury combined with or without lipopolysaccharide in rats,and investigate the emulsified isoflurane pretreatment on the inflammation reaction and lung injury induced by hepatic I/R in rats. A model of segmental hepatic ischemia-Reperfusion injury combined with or without lipopolysaccharide in rats were used in our study. The HO-1 inducer and inhibitor were used to investigate the role of HO-1 in the mechanism of protective effect of isoflurane.The follows are the main conclusions: Isoflurane pretreatment might reduce the inflammation reaction and live injury induced by hepatic ischemia-reperfusion combined with or without lipopolysaccharide in rats ; Isoflurane pretreatment might increase the HO-1 expression in live tissue hepatic ischemia-reperfusion , and which reduce inflammation reaction and liver injury;Ischemia-reperfusion in liver induced evident inflammation reaction and lung injury in rats, which were significantly attenuated by emulsified isoflurane pretreatment.
引文
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