摘要
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 explore the anti-inflammatory mechanism of the proteasome inhibitor MG-132 on rats with acute lung injury （ALI）. Methods 54 male SD rats were randomly divided into a control group,an ALl group,and a MG-132 group. LPS （5 mg/kg） was injected via tail vein in the ALl group and the MG-132 grouop, while the normal saline was given instead in the control group. MG-132 （10 mg/kg） was injected intraperitoneally at 30 min before LPS administration in the MG-132 group. Six rats in each group were sacrificed at 2,4, and 8h after normal saline or LPS administration. Then the following parameters were observed including pathology changes of lung tissue, wet to dry weight ratio of lung tissue （W/D）, the levels of ICAM-1 and TNF-ct in bronchoalveolar lavage fluid （BALF） by ELISA, and the protein level of nuclear factor -kappa B P65 （ NF-κB P65 ） in lung tissue by Western blot. Results The pathological observation showed the typical ALl performance, as obvious pulmonary tissue congestion, edema, a large number of inflammatory cells infiltration in the ALI group. These inflammatory performance were obviously alleviated in the MG-132 group. Compared with the control group ,the W/D, the levels of ICAM-1 and TNF-ot in BALF,and the expression of the protein NF-κB P65 in lung tissue at 2,4 and 6h in the ALl group were significantly increased （P 〈 0. 05 ）. Above parameters were significantly decreased in the MG-132 group compared with the ALl group. The expression of the protein NF-κB P65 was significantly positively related with the levels of ICAM-1 and TNF-α in BALF （ P 〈0. 01 ）. Conclusion MG-132 can suppress inflammatory response in endotoxin-indueed acute lung injury, which may be related to inhibition of NF-κB activation.
出处
《中国呼吸与危重监护杂志》
CAS
2014年第4期370-373,共4页
Chinese Journal of Respiratory and Critical Care Medicine
基金
广东省自然科学基金(编号:10151006001000012)
广东省医学科研基金(编号:A2013495)
