雌激素在脓毒症大鼠骨骼肌蛋白高分解代谢中的作用及其可能机制研究

Effect of estrogen on hypermetabolism of skeletal muscle protein insepsis rats and its underlying mechanism

目的:探讨雌激素在脓毒症大鼠骨骼肌蛋白高分解代谢中的作用及其可能机制。方法:采用腹腔内注射10 mg/kg内毒素制造脓毒症动物模型。将36只大鼠随机分为正常对照组、脓毒症组、脓毒症+雌激素注射组,每组12只。采用高效液相色谱分析法测定酪氨酸和三甲基组氨酸,实时聚合酶链式反应(RT-PCR)分析肌肉和下丘脑组织中白细胞介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)、骨骼肌萎缩基因(MuRF-1)、雌激素受体α(ER-α)和雌激素受体β(ER-β)mRNA的表达。结果:脓毒症组大鼠三甲基组氨酸(3-MH)、酪氨酸(Tyr)水平和萎缩基因MuRF-1 mRNA表达上调(P<0.05),而且中枢IL-1βmRNA和TNF-αmRNA表达量增加(P<0.05),ER-α、ER-βmRNA表达量减少(P<0.05)。给予皮下注射雌激素后,外周骨骼肌消耗及中枢炎症减轻,且有显著性差异(P<0.05)。下丘脑中雌激素受体表达与炎性递质表达呈负相关(P<0.05)。结论:雌激素能缓解骨骼肌高分解代谢,可能与其能减轻下丘脑炎症有关。

Objective： To investigate the effect of estrogen on hypermetabolism of skeletal muscle protein in rats with sepsis and its underlying mechanism. Methods： The animal model of sepsis were replicated by intraperitoneally injecting lipopolysaccharide（ LPS,10 mg / kg）. A total of 36 rats were randomly divided into normal control group,sepsis group,and sepsis plus estrogen group. Tyrosine and3-methyl-histidine（ 3-MH） were determined by high-performance liquid chromatography（ HPLC）. The relative expression of mRNA of muscle ring finger 1（ MuRF-1）,interleukin-1 β（ IL-1β）,tumor necrosis factor α（ TNF-α）,estrogen receptor α（ ER-α） and estrogen receptor β（ ER-β） in the muscle and hypothalamus were measured and analyzed by quantitiverealtimepolymerasechainreaction（ qRT-PCR）.Results： Compared with normal control group,sepsis group was found to have a significant higher level of Tyrosine and 3-MH,MuRF-1,IL-1β and TNF-α（ all P values 0. 05）,while a significant lower expression of ER-α and ER-β（ all P values 0. 05）. Compared with sepsis group,sepsis plus estrogen group was observed to have a lower expression of muscle wasting and hypothalamic inflammation（ P〈0. 05）.ER was inversely associated with hypothalamic inflammation（ P〈0. 05）. Conclusion： Estrogen,which can relieve muscle wasting in sepsis,may play a role in alleviating the hypothalamic inflammation.