内毒素血症时老年大鼠肝脏氧自由基代谢及热休克蛋白70的表达

The metabolism of oxygen free radical and expression of heat shock protein 70 in liver of old rats with experimentally induced endotoxemia

目的探讨内毒素血症时老年大鼠肝脏功能、自由基代谢的变化以及热休克蛋白70(HSP70)的表达。方法39只SD大鼠分成四组:老年对照组(n=7)、青年对照组(n=12)、老年内毒素组(n=8)、青年内毒素组(n=12)。采用尾静脉注射LPS(3mg/kg体重)制造内毒素模型,4h后取血及肝脏。检测肝功能(ALT、AST、DBIL、IBIL),血清及肝匀浆MDA、SOD水平,免疫组化测定肝脏HSP70表达。结果老年内毒素组较其对照组及青年内毒素组血清ALT及AST明显升高(P<0.05),血浆及肝匀浆MDA也均明显升高,SOD则明显下降(P<0.05)。肝脏HSP70表达老年对照组较青年对照组、老年内毒素组较青年内毒素组均明显增强(P<0.05)。结论内毒素血症时,老年大鼠存在更加严重的氧化/抗氧化比例失调,是老年组肝脏损伤明显的重要原因。老年内毒素组肝细胞的HSP70表达明显增强可能与其肝细胞内蛋白变性严重、存在更加强烈的氧化应激有关。

Objective To observe the difference in liver function, metabolism of oxygen free radical and expression of（ heat shock protein 70（HSP70） in liver between old and young rats. Methods Healthy male old and young SD rats were divided into four groups： old LPS group（ n = 8）, old control group（ n=8）, young LPS group （ n=8）, young control group （ n = 8）. Lipopolysacchride （LPS） was given （3 mg/kg body weight） with a intravenous bolus injection. The liver function（ALT, AST, DBIL, IBIL）, content of SOD and MDA in serum and liver, content of HSP70 in liver were determined by immunohistochemical analysis after injection for 4 h. Results The levels of ALT and AST in old LPS group were higher than in old control group and young LPS group （P 〈 0.05）. Compared with old control group and young LPS group, the activity of SOD in serum and liver decreased, but the content of MAD increased significantly in old LPS group. HSP70 levels of liver in LPS groups were higher than in control groups, respectively （P 〈 0.05 ）, and higher in old groups than in young groups, respectively（ P 〈 0.05 ）. The positive staining of HSP70 in liver of old LPS rats was stronger than young LPS rats（ P 〈 0.05）. Conclusion After injection of LPS, the disproportion of oxidation/antioxydation in old LPS rats is much more severe than in young rats. LPS is an important damage factor to liver of old rats. The up-regulation of HSP70 expression in liver of old LPS rats may be related to severe protein denaturation and intensive oxidative stress in liver.