Ghrelin对脓毒症大鼠肺组织亚硝酸化应激的影响

Effect of Ghrelin on Lung Nitrosative Stress in Septic Rats

【目的】观察ghrelin对脓毒症大鼠肺亚硝酸化应激的影响。【方法】采用盲肠结扎穿孔(CLP)方法制备脓毒症模型,24只雄性SD大鼠按随机区组设计方法随机分为3组:假手术组、脓毒症组(以CLP表示)和ghrelin组。ghrelin组于术后3 h及15 h腹腔注射ghrelin,各组于术后20 h采集标本。我们检测血清超氧化物歧化酶(SOD)活性、肺湿/干重、肺组织诱导型一氧化氮合成酶(iNOS)和硝基酪氨酸的表达水平。【结果】与假手术组[(93.17±0.54)%]对比,脓毒症组[(85.62±1.09)%]及ghrelin组[(88.71±0.86)%]的血清SOD活性显著降低,P<0.05。ghrelin组血清SOD活性较脓毒症组升高,但P>0.05;两组间的肺湿/干重比无明显统计学差异。术后20 h,与脓毒症组(1.08±0.05)比较,CLP术后20 h ghrelin组iNOS蛋白表达水平(0.87±0.03)下降,P<0.05。免疫组化结果显示ghrelin组硝基酪氨酸表达水平较脓毒症组低,P<0.05。【结论】ghrelin能下调肺组织iNOS蛋白的表达,减轻脓毒症大鼠肺组织亚硝酸化应激程度,并有提高血清SOD活性的趋势,但ghrelin没有改善肺湿/干重比。

[ Objective ] To investigate the effect of ghrelin on lung nitrosative stress in septic rats. [ Methods ] Sepsis model was induced by cecal ligation and puncture （CLP）. Twenty-four male SD rats were randomly divided into 3 groups according to randomized block design： sham-operated controls, sepsis （CLP） group, and ghrelin group. In ghrelin group, ghrelin was administered by intraperitoneal injection at 3 h and 15 h post-operation. Samples among each group were harvested at 20 h post-operation. We detected the activity of serum SOD, lung wet/dry weight, pulmonary iNOS and nitrotyrosine levels. [Results] The activity of serum SOD in sepsis group [ （85.62±1.09）% ] and ghrelin group [ （88.71 ±0.86）% ] was significantly decreased when compared with sham-operated controls [ （93.17 ±0.54）% ], P 〈 0.05. In ghrelin group, SOD activity was higher than that in sepsis group, but P 〉 0.05. There was no significant difference in lung wet/dry weight ratio between ghrelin group and sepsis group. Compared with sepsis group （ 1.08± 0.05）, pulmonary iNOS protein level in ghrelin group （0.87± 0.03） was reduced at 20 h post-operation. The result of immunohistochemistry revealed that the expression of nitrotyrosine in ghrelin group was lower than that in sepsis group, P 〈 0.05. [Conclusion] Ghrelin can down-regulate pulmonary iNOS protein expression and decrease nitrosative stress in CLP-induced septic rats. Besides, it tended to increase serum SOD activity. However, lung wet/dry weight ratio did not show any improvement by ghrelin administration.