血必净对大鼠急性肺损伤的保护作用

摘要

Objective:To investigate the protective effects of xuebijing (Traditional Chinese Medicine)on the acute lung injury in rats.Methods:Sixty Wistar rats were randomly divided into normal control group,model group,dexamethasone (10 mg/kg) group,xuebijing lowdose,medium-dose and high-dose groups(5,10,15 ml/kg),10 rats in each group.The acute lung injury model was induced by intraperitoneal injection of lipopolysaccharide 5 mg/kg.They were given relevant medicines intraperitoneally after modeling,once a day,for consecutive 7 days.Normal control group and acute lung injury(ALI) model group were given the equal bulk of saline by tail vein.7 days after treatment,the arterial blood samples were collected for detecting the arterial oxygen tension (PaO2) and the serum levels of malondialdehyde (MDA) and supemxide dismutase (SOD).Pulmonary tissue samples were obtained for the measurement of lung index(LI),wet/dry weight ratio(W/D),moisture content of lung [(W-D)/W] and the expressions of tumor necrosis factor-α(TNF-α),intedeukin-10 (IL-10) and high mobility group protein B1 (HMGB1).Results:Compared with normal control group,the levels of LI,W/D,(W-D)/W and PaO2 and the expressions of TNF-α,HMGB1 protein and the serum level of MDA in model group were increased,while the protein expression of IL-10 and the serum level of SOD were decreased;there was statistical significance(P ＜ 0.01).Compared with model group,the levels of LI,W/D,moisture content of lung and the protein expressions of TNF-α and HMGB1 and the serum level of MDA in xuebijing groups were decreased significantly,while PaO2 andthe protein expression of IL-10 and the serum level of SOD were increased,there was statistical significance (P ＜ 0.01).The effects in xuebijing high-dose group were better than those in xuebijing middle-dose and low-dose groups (P ＜ 0.01,P ＜ 0.05),Conclusion:Xuebijing could alleviate lipopolysaccharide-induced ALI,and its pharmacological mechanism may be related to down-regulation the protein expressions ofTNF-α and HMGB1 and the serum level of MDA and up-regulation the protein expression of IL-10 and the serum level of SOD and the highdose is more effective.%目的:研究血必净对急性肺损伤大鼠的保护作用.方法:60只Wistar大鼠随机分为正常组、模型组、地塞米松(10 mg/kg)组与血必净低、中、高剂量(5、10、15 ml/kg)组,每组10只.通过腹腔注射5mg/kg内毒素建立大鼠急性肺损伤模型,模型成功4h后腹腔注射给药,每天1次,连续7d;正常对照组和ALI模型组静脉注射等体积的生理盐水.7d后采集动脉血,检测动脉血氧分压(PaO2)、血清丙二醛(MDA)浓度和超氧化物歧化酶(SOD)的活性;取肺组织,检测肺系数(LI)、左肺湿/干质量比(W/D)、肺含水率[(W-D)/W],检测肿瘤坏死因子-α(TNF-α)、白细胞介素-10(IL-10)和高迁移率族蛋白-1(HMGB1)蛋白的表达.结果:与正常对照组比较,模型组大鼠LI、W/D、(W-D)/W,TNF-α和HMGB1蛋白表达以及血清MDA含量升高,PaO2,IL-10蛋白表达和血清SOD活性减弱,差异有统计学意义(P＜0.01);与模型组比较,血必净低、中、高剂量组大鼠LI、W/D及(W-D)/W,TNF-α和HMGB1蛋白表达以及血清MDA含量降低,PaO2,IL-10蛋白表达和血清SOD活性增强,差异有统计学意义(P＜0.01),其中血必净高剂量组效果较好,与中、低剂量组比较,差异有统计学意义(P＜0.05,P＜0.05).结论:血必净能减轻对内毒素诱导的急性肺损伤,其药理机制可能与下调TNF-α和HMGB1蛋白表达和血清MDA水平和上调IL-10蛋白表达和血清SOD活性有关,且以高剂量组效果较好.