重组人生长激素对肠源性内毒素血症大鼠急性肝损伤的影响

Effects of recombinant human growth hormone on acute liver injury induced by enterogenic endotoxemia in rats

目的观察重组人缺血生长激素(rh-GH)对肠源性内毒素血症(IETM)大鼠急性肝损伤的影响。方法 SD大鼠60只,随机分为正常对照(NC)组、肠梗阻缺血(IOI)组和生长激素(GH)组,其中每组又按不同时间点分为2个亚组,每个亚组10只大鼠。结扎回肠和肠系膜血管制备肠梗阻缺血大鼠模型,GH组另经肌肉注射2.25U/(kg·d)重组人生卡激素(rh-GH)。于制模后36h和72h分别测定各组大鼠的平均动脉压(MAP),血清丙氨酸氨基转移酶(ALT)和总胆红素(TBIL)水平;分别采用鲎试剂法和ELISA法测定血浆内毒素、肿瘤坏死因子(TNF)α和白细胞介素(IL)-1β的浓度;观察各组大鼠肝脏的组织病理学改变。结果与NC组相比,IOI组大鼠MAP在各时间点均显著降低(P<0.05),而GH组无明显改变;IOI组血浆内毒素含量在各时间点均明显高于NC组,而GH组仅在36h有所增加(P<0.05);IOI组和GH组在各时间点血浆TNFαI、L-1β、ALT和TBIL的浓度均显著高于NC组,但GH组较IOI组明显降低(P<0.05)。GH组在各时间点的肝脏病理改变均较IOI组明显改善。结论 rh-GH能显著改善IETM大鼠肝功能及肝脏组织病理学改变,其作用机制可能与减轻感染性休克的严重程度,降低血浆内毒素含量及炎症细胞因子的浓度有关。

Objective To investigate the effects of recombinant human growth hormone（rh-GH） on acute liver injury induced by enterogenic endotoxemia in rats.Methods Sixty rats were randomly assigned into three groups（20 each）： normal control group（NC group）,intestinal obstruction and ischemia group（IOI group） and growth hormone group（GH group）.Each group was divided again into two subgroups（10 each） according to different time intervals.The ileum and the mesenteric vessels were ligated to reproduce the IOI rat model（IOI group）.rh-GH [2.25U/（kg d）,i.m] was given to the IOI rats in GH group.The mean arterial blood pressure（MAP）,alanine transaminase（ALT） and total bilirubin（TBIL） were measured at the 36th and 72nd hour after treatment.The level of endotoxin,tumor necrosis factor α（TNF-α） and interleukin-1β（IL-1β） in plasma were determined by limulus test and ELISA.The histopathological changes of the liver were observed at each time interval.Results Compared with NC group,MAP decreased markedly in IOI group at different time points（P〈0.05）,while no obvious changes were found in GH group.The concentration of endotoxin in plasma was much higher in IOI group than in NC group at each time point,while increased only at the 36th hour after treatment in GH group（P〈0.05）.The concentrations of TNF-α,IL-1β,ALT and TBIL in plasma were significantly increased in IOI and GH group than in NC group at each time point,while decreased in GH group compared with that in IOI group（P〈0.05）.The histopathological changes in liver were obviously ameliorated in GH group than in IOI group at each time point.Conclusions rh-GH may obviously improve the function and histopathological changes in livers in IETM rats,and the results may be attributed to its function of ameliorating the severity of septic shock and reducing the endotoxin and inflammatory cytokines levels in plasma.