目的：研究舒芬太尼预处理对大鼠肝脏缺血再灌注损伤的保护作用及其可能的作用机制。方法健康SD大鼠30只，雌雄不拘，体质量220～270g，随机分为5组（n＝6）：假手术组（Ⅰ组）；肝缺血再灌注组（Ⅱ组）；5μg/kg舒芬太尼预处理组（Ⅲ组）；p38丝裂原活化蛋白激酶（p38MAPK）阻断剂SB203580＋Ⅲ组（Ⅳ组）和溶解剂二甲基亚砜（DMSO）组（Ⅴ组），至灌注240min时取材。抽取腹主动脉血测定血清中谷丙转氨酶（ALT）和谷草转氨酶（AST）活性；处死大鼠，收集肝组织，观察肝组织丙二醛（MDA）和超氧化物歧化酶（SOD）的变化；光学显微镜下观察肝组织病理学改变；Westernblotting法测定肝右叶组织p-p38MAPK的表达水平。结果与Ⅰ组相比，Ⅱ～Ⅴ组血清ALT、AST，肝组织MDA水平显著升高，出现病理学损伤；与Ⅱ组相比，Ⅲ组血清ALT、AST及肝组织MDA水平均明显下降，肝组织SOD水平明显升高，病理学损伤减轻，p-p38MAPK表达明显升高；与Ⅲ组相比，应用p38MAPK阻断剂SB203580，肝损伤加重；Ⅴ组与Ⅱ组各指标比较差异无统计学意义（P＞0．05）。结论舒芬太尼预处理可减轻大鼠肝缺血再灌注损伤，其机制可能是通过激活p38MAPK信号通路发挥作用。%Objective To study the protective effect of sufentanil preconditioning on hepatic ischemia-reperfusion injury in rats and to investigate the mechanisms whether may be by activating p38 MAPK signal pathway to promote p38 MAPK phosphoryla-tion .Methods Thirty SD rats(in either gender ,weighing 220-270 g) were randomly divided into five groups :Sham-operated group (Ⅰ) ,ischemia-reperfusion group(Ⅱ);sufentanil preconditioning group(5 μg/kg ,Ⅲ) ,SB203580(an inhibitor of p38 MAPK) group (Ⅳ) ,and dimethyl sulphoxide (DMSO) control group(Ⅴ) .Sample specimens were collected from each group at 240 minutes after reperfusion .Serum alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were measured by an automatic biochem-ical analyzer .Malondialdehyde(MDA) and superoxide dismutase(SOD) in liver tissue was measured .HE staining was used to ob-serve the hepatic pathological changes ,and to examine the expression of phosphor-p38 mitogen-activated protein kinases (p-p38 MAPK)of hepatic tissues by western blotting .Results Compared with group Ⅰ ,levels of AST ,ALT and MDA showed signifi-cantly increased in group Ⅱ-Ⅴ ,but levels of SOD decreased ,and obvious pathological changes were observed in the liver .In GroupⅢ significantly decreased the elevated levels of ASL ,ALT and MDA but increased levels of SOD ,and lessened hepatic pathological changes ,caused promoted p38 MAPK phosphorylation at 240 minutes after reperfusion .The protective effects of sufentanil precon-ditioning were abolished by SB203580 pretreatment .There were no significant differences between group Ⅴ and group Ⅱ .Conclu-sion Sufentanil preconditioning can reduce the hepatic ischemia-reperfusion injury .The protective mechanisms may be by activating p38 MAPK signal pathway to promote p38 MAPK phosphorylation .
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