性别差异对内毒素血症大鼠肺脏组织核因子-κB活化的影响

Influence of Genders on Activity of Nuclear Factor-Kappa B in Lungs in Endotoxemic Rats

目的探讨性别差异对内毒素血症大鼠肺脏组织核因子-κB(NF-κB)活化的影响。方法取40只清洁级Wistar大鼠,雌、雄各半,分为对照组(雌、雄各10只)和内毒素血症组(雌、雄各10只),采用腹腔注射内毒素5mg/kg制作动物模型,无菌留取肺脏组织标本,用凝胶阻滞迁移分析方法(EMSA)检测NF-κB的活化情况,同时检测大鼠血清中肿瘤坏死因子-α(TNF-α)及雌二醇(E2)含量。结果对照组雌、雄性大鼠肺脏组织有NF-κB微弱活化,分别为1.33±0.24和1.47±0.40,同时血清中TNF-α含量较少,分别为(0.75±0.16)ng/ml和(0.82±0.12)ng/ml,各项指标在雌、雄性大鼠间差异无统计学意义(P>0.05);注射内毒素后雌、雄性大鼠的NF-κB值分别为12.10±2.89和19.53±2.12,TNF-α值分别为(4.10±0.72)ng/ml和(6.37±1.29)ng/ml,较对照组明显升高(P<0.01),但是雌性大鼠各项指标的变化明显低于雄性大鼠(P<0.01)。对照组雌、雄性大鼠血清E2水平分别为(5.94±1.03)ng/L和(0.93±0.30)ng/L,注射内毒素后相应值为(6.13±1.31)ng/L和(1.06±0.26)ng/L,但两组间差异无统计学意义(P>0.05)。相关分析表明,雌、雄性内毒素血症大鼠肺脏组织NF-κB的活化与血清中TNF-α含量呈正相关(r=0.9211,P=0.013;r=0.9072,P=0.017),与E2含量呈负相关(r=-0.8875,P=0.017;r=-0.8723,P=0.022)。结论内毒素血症大鼠肺脏组织NF-κB的活化及血清中TNF-α的含量存在性别差异,内源性雌激素可能通过抑制NF-κB的活化介导了对雌性内毒素血症大鼠肺脏的保护作用。

Objective To investigate influence of genders on the activity of nuclear factor-kappa B （NF-κB） in lungs of endotoxemic rats. Methods Twenty female and 20 male Wistar rats were randomly divided into four groups as follow., female control group （n= 10）, male control group （n= 10）, male endotoxemic group （n= 10）, and female endotoxemic group （n = 10）. The endotoxemic rats model was made by injecting lipopolysaccharide （5 mg/kg） into the abdominal cavity. Tissue samples were collected from the lungs in different groups and electrophoresis mobility shift assay was used to measure the activity of NF-κB. The levels of serum TNF-α and estrogen were measured at the same time. Results There was no significant difference between the activities of NF-κB in male and female control groups （1.33±0.24 vs 1.47±0. 40）, and there was also no significant difference between other items in these groups as well （P〉0.05）. Yet, the activity of NF-κB （female： 12.10±2. 89; male： 19.53± 2.12） and the level of TNF-α [female： （4.10±0.72） ng/ml; male： （6.37±1.29） ng/ml] were significantly increased after injection of lipopolysaccharide （P〈0.01）, and the indices in female group were significantly lower than those in male group （P〈0. 01）. Correlation analysis showed that there was a positive relation between the activity of NF-κB in lungs and the level of TNF-α （female： r=0. 921 1, P=0. 013; male： r=0. 907 2, P=0. 017）, and there was a negative correlation between the activity of NF-κB and the level of estrogen （female： r= -0. 887 5, P= 0.017; male： r=0. 872 3, P=0.022） in both male endotoxemic group and female endotoxemic group （P〈0. 05）. Conclusion Gender may be one of the factors that influence the activity of NF-κB in the lungs of endotoxemic rats. While on the other hand, endogenous estrogen may protect the lungs of endotoxemic rats from injury by inhibiting the activity of NF-κB.