rhGH在大鼠肝脏缺血再灌注损伤中保护和修复的作用

PROTECTIVE AND REPAIRE OF RECOMBINANT HUMAN GROWTH HORMONE(rhGH)IN ISCHEMIC REPERFUSION INJURY OF RAT LIVER

目的探讨重组人生长激素(rhGH)在肝脏缺血再灌注损伤中的保护和修复作用及其机理。方法Pringles法建立180只肝脏缺血再灌注损伤模型,随机分为:A、B、C、D四组。A组:rhGH预处理组(n=50),B组:作为A组的对照组(n=50);A组:建模前连续7 d给予重组人生长激素(rhGH)针剂皮下注射0.2IU/100 g(体重)/d,B组分别给予等量的生理盐水。观察ALT、TNF-α、IL-1浕、丙二醛(MDA)肝脏能荷(Energy charge,EC)的变化,电镜观察肝脏超微结构变化。C组:rhGH治疗组(n=40),D组:作为C组的对照组(n=40)实验组建立模型后7d每天给予rhGH针剂皮下注射(0.2 IU/100 g),对照组分别给予等量的生理盐水;检测ALT、TNF-α、IL-1浕、EC、电镜观察肝脏超微结构的变化。结果A、B两组:A组ALT、TNF-a、、IL-1浕、和MDA在各个时间点的水平明显低于B组(P<0.05)。A组EC水平明显高于B组(P<0.05);B组电镜下可见肝窦内皮细胞破坏,肝细胞线粒体结构改变,A组肝细胞超微结构明显改善。C、D两组:ALT、TNF-α、明显降低,在7 d(和)或14d C组与D组有显著性差异;C组EC 7 d、14 d明显高于D组(P<0.05);C组肝细胞超微结构较D组亦有明显改善。结论rhGH可能通过抑制了细胞因子(TNF-α、IL-1浕),进一步减少MDA的生成,从而减轻了这些因子对肝脏损伤,rhGH对肝脏缺血再灌注损伤具有保护和修复作用;可以在肝脏缺血再灌注损伤后促进线粒体功能恢复,改善肝细胞能量代谢状态;rhGH在肝脏缺血再灌注损伤过程中,具有促进肝脏再生的作用。

Objective To investigate the role of rhGH in ischemic reperfusion injury of rat liver and its mechanism. Methods one hundred-eighty male rats were randomly divided into four groups： Group A pretreat with the rhGH （n = 50） , group B （n = 50） is the control group of A, group C treat with rhGH （ n = 40） , Group D （ n = 40） is the control group of C. The rats in group A were injected rhGH（0. 2 IU/100 g）seven clays before the ischemic reperfusion injury;in control group, rats was replaced by normal sodium, the rats in group C were injected（0. 2 IU/100 g ）seven clays after the ischemic reperfusion injury , in control group; rats was replaced by normal sodium. Serum levels of ALT,TNF-α and IL-1α were tested. Hepatic tissue was sectioned for to detect the level of EC and MDA. Also, uhrastructural characteristics histopathological characteristics were determined. Results Serum levels of ALT, TNF-α, IL- 1α and the contents of MDA in the control group were significantly higher than those group the rhGH were used（P 〈0. 05）. In two groups electronic microscopic revealed that the hepatic sinusoidal endothelial cells and the hepatocellular mitochondria were all injured in the control group. Pretreatment and treatment with the rhGH were able to significantly improved the pathological changes. Conclusion rhGH might confer the protection and repair the ischemic reperfusion injury of rat liver through reducing cytokine （IL-1α,TNF- αto down-regulate MDA. rhGH can promote mitochondrium ruction to improve EC level, liver function and enhance regeneration of liver cells after ischemic reperfusion injury.