丙泊酚联合热毒宁注射液对内毒素所致大鼠急性肺损伤及ERK1/2-NF-κB通路的影响

Effects of Propofol Combined with Reduning Injection on Endotoxin-induced Acute Lung Injury and ERK1/2-NF-κB Pathway in Rats

目的探讨丙泊酚联合热毒宁注射液对内毒素所致大鼠急性肺损伤及ERK1/2-NF-κB通路的影响。方法选取SD大鼠100只,随机分为对照组、模型组、丙泊酚组、热毒宁组、联合组,每组20只。模型组、丙泊酚组、热毒宁组、联合组经脂多糖诱导大鼠急性肺损伤模型,建模成功后,丙泊酚组给予丙泊酚50.0 mg/kg、热毒宁组给予热毒宁50.0 mg/kg、联合组给予丙泊酚和热毒宁各50.0 mg/kg;对照组和模型组给予等体积生理盐水,均持续给药7 d。在第7天处死大鼠,分离肺组织进行肺/体重测定及肺损伤评分,测定5组肺组织ERK1/2和NF-κB的mRNA及蛋白表达水平,比较5组肺组织白介素-2(IL-2)、白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)的蛋白表达水平。结果与对照组比较,模型组肺/体比值、肺损伤评分、ERK1/2和NF-κB的mRNA表达水平、ERK1/2、NF-κB、IL-2、IL-6、TNF-α的蛋白表达水平显著升高(P<0.05);与模型组比较,丙泊酚组、热毒宁组、联合组肺/体比值、肺损伤评分、ERK1/2和NF-κB的mRNA表达水平、ERK1/2、NF-κB、IL-2、IL-6、TNF-α的蛋白表达水平显著降低,且联合组上述指标显著低于丙泊酚组、热毒宁组(P<0.05)。结论丙泊酚联合热毒宁注射液可减轻内毒素所致大鼠急性肺损伤引发的炎症反应;其机制与丙泊酚联合热毒宁注射液抑制ERK1/2-NF-κB通路基因蛋白及其下游炎性因子的表达有关。

Objective To investigate the effects of propofol combined with Reduning injection on endotoxin-induced acute lung injury(ALI) and ERK1/2-NF-κB pathway in rats. Methods A total of 100 SD rats were randomly divided into control group(n=20), model group(n=20), Propofol group(n=20), Reduning group(n=20) and combination group(n=20). The ALI models were induced by lipopolysaccharide in model group, Propofol group, Reduning group and combination group. After the models were established successfully, Propofol 50.0 mg/kg, Reduning 50.0 mg/kg, and both Propofol 50.0 mg/kg and Reduning 50.0 mg/kg were administered in Propofol group, Reduning group and combination group respectively, and normal saline of equal volume were administered in control group and model group for 7 consecutive days. On the 7th day, rats were sacrificed, and lung tissues were separated for lung/body weight measurement and lung injury score. The mRNA and protein expression levels of ERK1/2 and NF-κ B in lung tissues of five groups were measured. The levels of interleukin(IL)-2, IL-6 and tumor necrosis factor-α(TNF-α) in lung tissues of five groups were compared. Results Compared with the control group, the lung/body weight ratio, lung injury score, ERK1/2 and NF-κ B mRNA expression and the protein expression levels of ERK1/2, NF-κ B mRNA, IL-2, IL-6, TNF-α in the model group were significantly higher(P<0.05). Compared with the model group, the lung/body weight ratio, lung injury score, ERK1/2 and NF-κ B mRNA expression, ERK1/2 and NF-κ B protein expression, as well as expression levels of IL-2, IL-6 and TNF-α in the Propofol group, the Reduning group and the combination group were significantly lower, and the above indicators were significantly lower in combination group than in Propofol group and the Reduning group(P<0.05). Conclusion Propofol combined with Reduning injection can alleviate the inflammation induced by endotoxin-induced ALI in rats, and its mechanism is related to the inhibition of ERK1/2-NF-κB pathway gene and protein and its downstream inflammatory factors by Propofol combined with Reduning injection.