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目的探讨蛋白酶体抑制剂MG-132对急性肺损伤(ALI)大鼠的抗炎作用机制。方法将雄性SD大鼠54只随机分为对照组、ALI组和MG-132组,每组18只。对照组尾静脉注入生理盐水,ALI组、MG-132组尾静脉注射脂多糖(LPS)5 mg/kg,MG-132组于实验前30 min腹腔注射MG-132 10 mg/kg。三组动物在注射生理盐水或LPS后2、4、8 h各随机处死6只,观察肺组织病理学变化,测定肺组织湿重/干重比值(W/D),酶联免疫吸附法(ELISA)检测大鼠支气管肺泡灌洗液(BALF)中细胞间粘附分子1(ICAM-1)、肿瘤坏死因子α(TNF-α)的表达,Western blot法测定肺组织核因子κB(NF-κB)P65蛋白的表达。结果 ALI组大鼠病理切片可见明显肺组织充血、水肿、大量炎性细胞浸润等典型ALI表现,MG-132组病理学损伤明显减轻。与对照组比较,ALI组大鼠2、4、8 h肺组织W/D比值及BALF中ICAM-1、TNF-α的表达、肺组织NF-κB P65蛋白的表达均明显升高(P<0.05),MG-132组大鼠2、4、8 h肺组织W/D比值及BALF中ICAM-1、TNF-α的表达、肺组织NF-κB P65蛋白的表达均较ALI组明显降低(P<0.05)。肺组织NF-κB P65蛋白的表达与ICAM-1、TNF-α的表达呈显著正相关(P<0.01)。结论 MG-132可改善内毒素性急性肺损伤炎症反应,其抗炎作用可能与抑制NF-κB信号通路的激活有关。
Objective To investigate the anti-inflammatory mechanism of proteasome inhibitor MG-132 in acute lung injury (ALI) rats. Methods 54 male SD rats were randomly divided into control group, ALI group and MG-132 group, with 18 rats in each group. Rats in MG-132 group were injected with 5 mg / kg lipopolysaccharide (LPS) into MG-132 group, and MG-132 10 mg / kg intraperitoneally 30 minutes before the experiment. Three animals were randomly sacrificed at 2, 4 and 8 h after injection of normal saline or LPS, respectively. The pathological changes of lung tissue were observed. The W / D ratio of lung tissue and enzyme linked immunosorbent assay ELISA was used to detect the expression of intercellular adhesion molecule 1 (ICAM-1) and tumor necrosis factor-α (TNF-α) in bronchoalveolar lavage fluid (BALF) and the expression of nuclear factor kappa B κB) P65 protein expression. Results The pathological changes of ALI group showed typical ALI manifestations such as pulmonary congestion, edema and inflammatory cell infiltration. The pathological damage of MG-132 group was significantly reduced. Compared with the control group, the W / D ratio of lung tissue, the expression of ICAM-1 and TNF-α in BALF and the expression of NF-κB P65 protein in lung tissue in ALI group were significantly increased at 2, 4 and 8 h (P < 0.05). The W / D ratio of lung tissue, the expression of ICAM-1 and TNF-α in BALF, the expression of NF-κB P65 protein in lung tissue of MG-132 group were significantly lower than those of ALI group P <0.05). The expression of NF-κB P65 in lung tissue was positively correlated with the expression of ICAM-1 and TNF-α (P <0.01). Conclusion MG-132 can improve the inflammatory response of LPS-induced acute lung injury and its anti-inflammatory effect may be related to the inhibition of the activation of NF-κB signaling pathway.