性别差异对脓毒症大鼠肺组织Toll样受体4及髓样分化蛋白-2基因表达的影响

Influence of sexual difference on expression of Toll - like receptor 4 and myeloid differential protein - 2 mRNA in the lung in septic rats

目的 探讨性别差异对脓毒症大鼠肺组织Toll样受体4(TLR4)、髓样分化蛋白-2(MD-2)和 肿瘤坏死因子-α(TNF-α)基因表达的影响。方法 脂多糖(LPS)刺激前后留取雌性和雄性大鼠肺组织标本, 提取总RNA,采用半定量逆转录-聚合酶链反应(RT-PCR)测定TLR4、MD-2和TNF-α的基因表达情况, 采用放射免疫测定法检测大鼠血浆雌二醇(E2)含量。结果 正常雌性和雄性大鼠肺组织均可表达少量 TLR4、MD-2和TNF-α基因,性别间差异均无显著性(P均>0．05),但脓毒症雌性大鼠各项指标表达均明 显弱于雄性(P均<0．01)。相关分析表明,雌性和雄性脓毒症大鼠肺组织TLR4、TNF-α的mRNA表达与血 浆E2含量均呈显著负相关(P均<0．05)。结论 LPS诱导的肺组织TLR4信号转导通路活化存在性别差异, 内源性雌激素作用可能导致雌性脓毒症大鼠对LPS的反应性弱于雄性。

Objective To investigate the influence of gender on the gene expression of Toll-like receptor 4 （TLR4）, myeloid differential protein-2 （MD-2） and tumor necrosis factor-α （TNF-α） in the lung in septic rats. Methods The total RNA from normal and lipopolysaccharide （LPS）-challenged rats was extracted by Trizol reagent. The gene expressions of TLR4, MD-2 and TNF-α mRNA were measured by semi-quantitative reverse transcription polymerase chain reaction （RT-PCR）. Plasma estradiol （E2） content was determined by radioimmunoassay. Results The gene of TLR4, MD-2 and TNF-α were expressed in the lungs in normal rats, and there was no significant difference between male and female rats （P〉0. 05）. After LPS challenge, the gene expression were markedly up-egulated at 2 hours, and the gene expressions of TLR4, MD-2 and TNF-α were significantly lower in female group than those in male group （all P〈0. 01）. Conclusion There are marked difference in activation of TLR4 signal transduction in the lung when stimulated by LPS between male group and female group. The response to LPS is lower in female septic rats than in male septic rats, which might be associated to the effect of endogenous estrogen.