sh-RNA沉默HMGB1对脓毒症小鼠肺损伤保护作用研究

Protective effect of sh-RNA silencing HMGB1 on lung injury in septic mice

目的探讨短发夹RNA(sh-RNA)沉默高迁移率族蛋白1(HMGB1)对脓毒症小鼠肺损伤的保护作用。方法采用脂多糖(LPS)诱导小鼠脓毒症模型,随机分为磷酸盐缓冲液(PBS)组、LPS组、LPS+sh-RNA阴性对照(sh-NC)组和LPS+sh-HMGB1组。采用酶联免疫吸附试验(ELISA)检测各组小鼠血清前列腺素E2(PGE2)及炎症细胞因子[肿瘤坏死因子-α(TNF-α)、白细胞介素(IL-1β)和IL-6]表达水平,并且检测各组小鼠肺组织髓过氧化物酶(MPO)活性及组织细胞凋亡情况。结果LPS组小鼠PGE2、TNF-α、IL-1β、IL-6表达水平均明显高于PBS组,LPS+sh-HMGB1组小鼠PGE2、TNF-α、IL-1β、IL-6表达水平均明显低于LPS+sh-NC组,LPS组小鼠肺组织MPO活性、凋亡细胞比例均明显高于PBS组,LPS+sh-HMGB1组小鼠肺组织MPO活性、凋亡细胞比例均明显低于LPS+sh-NC组,差异均有统计学意义(P<0.05)。结论LPS诱导的脓毒症可刺激炎性反应,并对肺组织造成明显损伤。而体内沉默HMGB1可抑制炎性反应,对肺损伤具有保护作用。

Objective To investigate the protective effect of sh-RNA silencing high mobility group box 1(HMGB1)on lung injury in sepsis mice.Methods The mice sepsis models were induced by lipopolysaccharide(LPS)and randomly divided into the phosphate buffer(PBS)group,LPS group,LPS+sh-RNA negative control(sh-NC)group and LPS+sh-HMGB1 group.The expression levels of serum prostaglandin E2(PGE2)and inflammatory factors(TNF-α,IL-1βand IL-6)were determined by the enzyme-linked immunosorbent assay(ELISA),and the activity of myeloperoxidase(MPO)in lung tissues and apoptosis of tissue cells in each group were detected.Results The expression levels of PGE2,TNF-α,IL-1βand IL-6 in the LPS group were significantly higher than those in the PBS group.The expression levels of PGE2,TNF-α,IL-1βand IL-6 in the LPS+sh-HMGB1 group were significantly lower than those in the LPS+sh-NC group(P<0.05).The activity of MPO and the proportion of apoptotic cells in the LPS group were significantly higher than those in the PBS group,while the activity of MPO and the proportion of apoptotic cells in the LPS+sh-HMGB1 group were significantly lower than those in the LPS+sh-NC group,and the differences were statistically significant(P<0.05).Conclusion LPS-induced sepsis could stimulate the inflammatory response and cause significant damage to lung tissue.In vivo silencing HMGB1 could inhibit the inflammation response and has the protective effect on lung injury.