瘦素对肠缺血/再灌注损伤大鼠肝脏功能的影响及其机制

目的:探讨瘦素(leptin)对大鼠肠缺血/再灌注(I/R)损伤时肝脏的保护作用及其机制。方法:99只Wistar大鼠随机分成11组:假手术组,肠缺血45min再灌注15min、30min、1h、3h、6h的肠I/R损伤组和相应时间点的leptin治疗组,每组9只大鼠。肠I/R损伤组和leptin治疗组建立大鼠肠I/R损伤模型;leptin治疗组于再灌注的同时腹腔注射leptin0.2mg/kg。假手术组术后1h处死,其余各组大鼠于相应时间点处死,检测血清丙氨酸转氨酶(ALT),肝组织中白细胞介素-6(IL-6)、IL-10和超氧化物歧化酶(SOD)水平的动态变化。结果:肠I/R组血清ALT随着时间变化逐渐升高,肝组织中的IL-6水平于再灌注3h显著升高,而IL-10水平基本处于平稳的波动状态,SOD活性于再灌注早期呈略微下降趋势,1h后逐步回升至假手术组水平;leptin治疗后血清ALT水平基本稳定在较低水平,再灌注3h后,肝组织IL-6水平较损伤组明显降低,同时SOD活性显著提高,IL-10水平于再灌注15min时突然增高,随即恢复到假手术组水平。结论:leptin对大鼠肠I/R造成的肝脏功能损伤具有改善作用,可能与其调节肝组织中的细胞因子释放、提高肝脏的抗氧化损伤能力有关。

Effect of leptin on liver function and its possible mechanism in intestinal ischemia/reperfusion injury in rats

Objective:To explore the possible protective effect of leptin on liver against intestinal ischemia/reperfusion(I/R) injury in rat and its underlying mechanisms.Methods:Ninety-nine rats were randomly divided into eleven groups (each n=9): sham group, ischemia of intestine for 45minutes and reperfusion for 15 minutes,30 minutes, 1 hour,3 hours,6 hours groups, and five corresponding I/R with leptin treatment groups.After reperfusion, serum samples were collected to determine alarmine transferase (ALT) level. The concentrations of interleukin-6(IL-6), IL-10 and superoxide dismutase (SOD) activity in liver tissues were also determined.Results:Concentration of serum ALT increased with elapse of time after intesine I/R injury. In liver tissue, level of IL-6 was abruptly elevated at 3 hours after reperfusion, while a fluctuation of the IL-10 concentration was found. SOD activity was decreased slightly in the early phase of reperfusion and returned to the base level after 1 hour. In leptin-treatment group, ALT was maintained at a relatively low level compared with the intestine I/R group. After reperfusion of 3 hours, the concentration of IL-6 was decreased, while SOD activity was increased significantly. The level of IL-10 was elevated after reperfusion of 15 minutes, and immediately reduced to the base-level.Conclusion:Leptin played a protective role against liver damage caused by intestine I/R injury, which was probably mediated by the cytokine release regulation and improvement of anti-oxidation ability.