脂联素对脓毒症大鼠早、晚期炎症介质表达的影响

Effect of adiponectin on early and late cytokine expression in LPS-induced septic rat

目的 研究脂联素（adiponectin，APN）对内毒素（lipopolysaccharide，LPS）诱导的脓毒症大鼠早、晚期炎症介质表达的影响。方法 将96只健康雄性Wistar大鼠按随机数字表法分为4组（每组24只）：对照组（c组）、模型组（LPS组）、APN预处理组（APN＋LPS组）及APN后处理组（LPS＋APN组）。各组分别于注射LPS（7．5mg／kg）或0．9％氯化钠溶液（Ns）后4、24、48、72h时随机活杀6只大鼠并留取血和肺组织标本。采用酶联免疫吸附法（ELISA）检测各组大鼠血浆肿瘤坏死因子哪（tumornecrosis factor-α，TNF-α）和白细胞介素-6（interleukin-6，IL-6）的含量。采用实时荧光定量聚合酶链反应（real-timePCR）测定肺组织高迁移率族蛋白B1（highmobilitygroupbox1，HMGBl）mRNA的表达水平，并绘制各组大鼠的生存曲线。结果 与c组相比，LPS组血浆TNFq（17．13±1．04）VS（0．45±0．29）和IL-6（201．98±1．25）VS（9．81±0．69）水平于注射LPS后4h显著升高（P〈0．05），24h时已明显下降；而APN＋LPS组和LPS＋APN组上升的幅度明显低于LPS组（P〈0．05）。LPS组（2．36±0．25）肺组织HMGBlmRNA表达水平在24h时达高峰（P＜0．05），并维持至48h后开始下降。APN＋LPS组和LPS＋APN组HMGBlmRNA表达较LPS组呈减少趋势（1．41±0．42）VS（2．36±0．25）；（1．42±0．38）VS（2．36±0．25）（P〈0．05）。APN＋LPS组和LPS＋APN组大鼠生存率明显高于LPS组（70％VS30％；60％VS30％，P〈O．05）。结论 APN可显著提高脓毒症大鼠的生存率，对早、晚期炎症介质TNF-ct、IL-6、HMGBl的表达有明显抑制作用。

Objective To investigate the effect of adiponectin on early and late cytokine expression in lipopolysaccharide （LPS） induced septic rats. Methods Ninety-six Wistar male rats were randomly divided into 4 groups： control group （C group）, model group （LPS group）, early adiponectin treatment group （APN＋LPS group）, late adiponectin treatment group （LPS＋APN group）. At 4, 24, 48 and 72 hours after administration of LPS or NS, six rats were randomly sacrificed in each group. Serum samples and the lung tissue samples were collected. The levels of tumor necrosis factor-α（TNF-α） and interleukin-6（IL-6） in plasma were determined by enzyme linked immunosorbent assay （ELISA）. Lung tissues were sampled. The expression of high mobility group box 1 （HMGB1） mRNA in the lung tissue were detected by Quantitative real-time reverse transcription-polymerase chain reaction （RT-PCR） with GAPDH as an internal standard. The survival curves in 4 groups were drawn. Results The levels of TNF-α （17.13±1.04） vs. （0.45±0.29） and IL-6 （201.98±1.25） vs（9.81±0.69） in plasma in LPS group were higher than those in C group at 4 hours （P〈0.05）, the trend of whichlast for 24 hours. TNF-α and IL-6 levels of both APN＋LPS group and LPS＋APN group were reduced as compared with LPS group（P〈0.05 ）. The HMGBlmRNA expression level in lung tissue was measurable at 24 hours in LPS group（2.36±0.25,P〈0.05）, which maintained a high level up to 48 hours after administration of LPS. The HMGB1 mRNA expression level in both APN＋LPS group and LPS＋APN group were decreased as compared with that of LPS group （1.41±0.42 vs 2.36±0.25; 1.42±0.38 vs 2.36±0.25, iespectively,P〈O.O5）.The survival rate of rats in both APN＋LPS group and LPS＋APN group were higher than that of LPS group （70% vs. 30% ; 60% vs. 30%, P〈0.05）. Conclusion Adiponeetin can significantly raise the survival rate of septic rats. It also can inhibit the early and late eytokines expression in LPS induced septic rats.