性别差异对脓毒症大鼠心肌Toll样受体4和髓样分化蛋白-2基因表达的影响

Influence of gender differences on gene expression of TLR4 and MD-2 in myocardium in septic rats

目的:探讨性别差异对脓毒症大鼠心肌Toll样受体4(TLR4)和髓样分化蛋白-2(MD-2)及肿瘤坏死因子-α(TNF-α)基因表达的影响。方法:取40只清洁级Wistar大鼠,雌雄各半,分为正常雌雄性对照组(各10只),雌雄性脓毒症组(各10只)。采用腹腔注射5mg/kg内毒素(LPS)制作脓毒症大鼠模型,无菌留取大鼠心肌组织标本,利用RT-PCR法检测心肌组织TLR4、MD-2以及TNF-α基因表达,利用放免法检测大鼠血浆雌二醇含量。结果:正常雌雄性大鼠心肌组织均可表达少量TLR4、MD-2及TNF-α基因,两组差异无统计学意义(P>0.05),但是注射LPS后雌性大鼠心肌组织各项指标明显低于雄性大鼠(P<0.01)。相关分析表明,雌性及雄性脓毒症大鼠心肌组织TLR4及TNF-α基因表达与相应性别大鼠血浆中雌二醇含量呈显著负相关(P<0.05)。结论:LPS注射后大鼠心肌组织TLR4、MD-2及TNF-α基因表达存在性别差异,内源性雌激素的作用可能导致雌性脓毒症大鼠心肌组织对LPS的反应性弱于雄性。

Objective： To investigate the influence of gender differences on gene expression of Toll-like receptor 4 （TLR4）, myeloid differential protein-2 （MD-2） and tumor necrosis factor-alpha （TNF-α） in myocardium in septic rats. Methods：Sepsis was replicated by injected LPS （5mg/kg） into abdominal cavity. Male and female rats were sacrificed at 2 hours after injected LPS, the gene expression of TLR4, MD-2 and TNF-ct in myocardium were measured by semi-quantitative reverse transcription polymerase chain reaction （RT-PCR）. The level of plasma estrogen were measured also. Results：The gene of TLR4, MD-2 and TNF-α were expressed in very low values in normal male and female rats. After stimulated by LPS 2 hours later, the gene expression was markedly up-regulated, and the gene expression in female group lower than that in male group （P 〈0.01 ）. The gene expression of TLR4 and TNF-α in myocardium of female or male septic rats have significantly negative correlation with the level of plasma estrogen （P 〈 0.05 ）. Conclusion ：There are signiticantly gender differences in activation of TLR4 signal transduction in myocardium when stimulated by LPS. The reaction to LPS is lower in female septic rats than that in male septic rats.