长托宁对急性肺损伤家兔肺组织NF-κB活性的影响

The Effect of PHCD on the Expression of NF-κB in Acute Lung Injury Rabbits

目的探讨长托宁(PHCD)在LPS所致的急性肺损伤家兔中的作用及保护机制。方法 20只新西兰兔随机分为4组:空白组、模型组、PHCD低剂量组、PHCD高剂量组。其中PHCD低、高剂量组于LPS注入前30 min分别腹腔内注射PHCD 0.2 mg/kg和2 mg/kg,采用HE染色观察各组肺组织形态学的差异、免疫组化和Western blot检测NF-κB激活情况。结果 HE染色显示模型组肺泡隔明显增厚,有大量炎性细胞浸润,可见较多中性粒细胞,偶见支气管黏膜脱落。PHCD处理后,炎症反应有所减轻,并与给药剂量的增加而降低。免疫组化显示,空白组家兔支气管黏膜上皮和肺间质中仅见少量散在的NF-κB阳性细胞,模型组支气管黏膜、肺间质、肺泡腔及血管内皮细胞中NF-κB阳性细胞明显增多。长托宁处理后NF-κB阳性细胞较模型组有所减少,以高剂量组减少最明显。Western blot显示模型组肺组织细胞核内NF-κB的p65水平显著高于阴性对照组,PHCD处理后p65水平明显下降。结论 PHCD能有效减轻ALI家兔肺组织中的炎症反应,其机制可能与下调NF-κB活性有关。

Objective To observe the effect and protective mechanism of PHCD on the expression of NF-κB in acute lung injury（ALI） rabbits induced by lipopolysaccharide（LPS）.Method 20 New Zealand rabbits were randomly divided into 4 groups：control group,model group,low and high PHCD-dose group.The low and high PHCD groups were intraperitoneally administrated by PHCD（0.2mg/kg and 2mg/kg,respectively） 30min before LPS injection,then the differences of lung morphology were observed.Immunohistochemistry and Western blot were used to detect the activation of NF-κB.Result Histomorphology showed that alveolar septum became thick and infiltrated with large amount of inflammation cells,and Bronchial mucosa occasionally fell off.After the treatment of PHCD,the inflammatory response was reduced in dose-dependent manner.Immunohistochemistry showed that only a few scattered NF-κB positive cells in the bronchial epithelial and interstitial lung in the control group,while in the model group,the NF-κB-positive cells increased significantly in the mucosa,pulmonary interstitial and alveolar and vascular endothelial.After PHCD treated,NF-κB positive cells were less than the model group,and the high dose group was more obvious.Western blot showed that in the lung tissue of model group,the p65 level of NF-κB was significantly higher than the negative control group,and p65 were significantly decreased after PHCD treatment.Conclusion PHCD could effectively reduce inflammation reaction in the ALI rabbits,which may be associated with the downregulation of NF-κB activity.