Effect Of Estrogen On Hypermetabolism Of Skeletal Muscle Protein In Sepsis Rats And Its Underlying Mechanism

Part one:The effect of estrogen on hypermetabolism of skeletal muscle protein in sepsis ratsBackground Sepsis can lead to a series of metabolic disorders, one of which is the high metabolism of skeletal muscle. At the same time, most of the patients with severe estrogen levels of disorder. Studies have shown that estrogen can protective various organs of the body, while little studies has shown the effects of estrogen on the skeletal muscle induced by sepsis.Objective To investigate the effect of estrogen on hypermetabolism of skeletal muscle protein in sepsis rats.Methods The model of sepsis rats were replicated by intraperitoneally injecting lipopolysaccharide (LPS, 10mg/kg). A total of 18 rats were randomly divided into normal control group, sepsis group, sepsis plus estrogen group. Tyrosine and 3-methyl-histidine (3-MH) were determined by high-performance liquid chromatography (HPLC). The relative mRNA of muscle ring finger 1 (MuRF-1) and Muscle atrophy F-box (MAFbx) were measured and analyzed by quantitative real time polymerase chain reaction (qRT-PCR) in the muscle.Results Compared with normal control group, sepsis group was found a significant higher level of Tyrosine and 3-MH, MuRF-land MAFbx (all p values< 0.05), Compared with sepsis group, sepsis plus estrogen group was observed a lower expression of muscle wasting and MuRF-1 mRNA (all p values< 0.05), and there was no significant difference in MAFbx.Conclusion Estrogen can relieve muscle wasting in sepsis rats.Part two:The underlying mechanism of estrogen on relieving hypermetabolism of skeletal muscle protein in sepsis ratsBackground In the first part, we demonstrated that the estrogen can relieve muscle wasting in sepsis rats., but its specific mechanism was not clear. According to the theory of "sepsis-inflammatory cytokine-hypothalamic neuropeptide", we further observe the effect of estrogen on hypothalamic central inflammatory cytokines and hypothalamic neuropeptide.Objective To investigate the underlying mechanism of estrogen on relieving hypermetabolism of skeletal muscle protein in sepsis rats.Methods The model of sepsis rats were replicated by intraperitoneally injecting lipopolysaccharide (LPS, 10mg/kg). A total of 18 rats were randomly divided into normal control group, sepsis group, sepsis plus estrogen group. The relative mRNA of interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), estrogen receptor α(ER-α), estrogen receptor β (ER-P), proopiomelanocortin(POMC), agouti-related protein(AgRP) and Neuropeptide Y(NPY) were measured and analyzed by quantificational real time polymerase chain reaction (qRT-PCR) in the muscle and hypothalamus.Results compared with normal control group, sepsis group was found a significant higher level of IL-1β α, TNF-α and POMC mRNA (all p values< 0.05), while a significant lower expression of ER-α, ER-β, AgRP and NPY mRNA (all p values< 0.05). Compared with sepsis group, sepsis plus estrogen group was observed a lower expression of hypothalamic inflammation, POMC and NPY mRNA (all p values< 0.05), while a significant higher expression of ER-α, ER-β and AgRP mRNA (all p values< 0.01). There was a negative correlation between ER and hypothalamic inflammation (all p values< 0.05).Conclusion Estrogen, which can relieve muscle wasting in sepsis rats, may play a role in alleviating the hypothalamic inflammation.