性别差异对脓毒症大鼠肝脏Toll样受体4和髓样分化蛋白-2基因表达的影响

The influence of gender differences on gene expression of TLR4 and MD-2 in livers in septic rats

目的探讨性别差异对脓毒症大鼠肝脏组织Toll样受体4(TLR4)和髓样分化蛋白- 2(MD-2)基因表达的影响。方法以脂多糖(LPS)按5 mg/kg体重由大鼠腹腔注射制作脓毒症动物模型,注射后2 h留取肝脏组织检测TLR4、MD-2和肿瘤坏死因子-α(TNF-α)基因表达,同时测定各组大鼠血浆中丙氨酸氨基转移酶(ALT)及雌二醇含量。结果正常雌雄性大鼠肝脏组织均可表达少量TLR4、MD-2、TNF-α基因,其中雌性组分别为0．175±0．034、0．211±0．044、0．201±0．068; 雄性组分别为0．205±0．061、0．243±0．049、0．243±0．063,两组数据差异无统计学意义(P> 0．05),但LPS刺激后雌性大鼠肝脏组织上述指标分别为0．615±0．089、0．708±0．181、0．730± 0．118,血浆中ALT含量为(81．07±10．72)U／L;雄性组分别为0．723±0．091、1．123±0．272、 0．881±0．156,ALT含量为(106．39±14．21)U／L,雌性组各项指标均明显低于雄性大鼠(P< 0．05)。相关分析表明雌性及雄性脓毒症大鼠肝脏组织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刺激后大鼠肝脏组织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肝脏组织损伤较雄性轻。

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 livers in septic rats. Methods The rat septic model was made by injecting LPS （5 mg/kg） into abdominal cavity. Total RNA of livers from normal and septic rats extracted by Trizol reagent and the gene expression of TLR4, MD-2 and TNF-α were detected by semi-quantitative reverse transcription polymerase chain reaction （RT-PCR）. The level of plasma ALT and estrogen were measured also. Results The gene of TLR4, MD-2 and TNF-α was expressed in livers and the expression levels in normal male and female rats were 0.175 ± 0.034, 0.211± 0.044, 0.201± 0.068, and 0.205± 0.061, 0.243 ± 0. 049, 0. 243 ± 0. 063, respectively （P 〉 0.05）. After stimulation by LPS, the gene expression and the level of plasma ALT were markedly up-regulated, and the index in female group was （0. 615 ± 0. 089, 0.708 ±0.181, 0.730± 0.118, 81.07± 10.72） U/L, significantly lower than that in male group （0. 723 ± 0.091, 1. 123 ± 0. 272, 0. 881 ± 0. 156,106.39 ± 14.21） U/L respectively （P〈 0.01）. The gene expression of TLR4 and TNF-α in livers of female or male septic rats had a significantly negative correlation with the level of plasma estrogen （P 〈 0.05）. Conclusion There are significant gender differences in the gene expression of TLR4, MD-2 and TNF-α in livers in septic rats. Estrogen may decrease the injury of livers in septic rats.