The Mechanism Research And Protect Effect Of Ligustrazine On ALI/ARDS Rats

Objective: To observe the influence of Ligustrazine on pulmonary surfactant in acute lung injury(ALI)/acute respiratory distress syndrome(ARDS)rats and explor the protective effect of ligustrazine on lung injury and its mechanism,and to provide reliable basis for ligustrazine applicated in clinical treatment of lung injury.Methods : 35 healthy male SD rats weighing about 200~250g were randomly divided into normal control group C(group C)(n=5),oleic acid group(group OA)(n=15),ligustrazine group(group L)(n=15).The rats from group OA and group L,which divided into five groups according to 1h,3h and 5h were treated with intravenous injection of oleic acid(0.16ml/kg)to establish acute lung injury model.Group C was injected with the same amount of saline.In group L rats,ligustrazine(40mg/kg)was accepted immediately after injection of oleic acid,group C and group OA rats were injected with the same volume of saline.The blood gas analysis was performed at different time in rats from three groups,the lung wet / dry weight ratio(W/D value)was calculated,the pathological changes in lung tissues were observed by HE staining.The enzyme linked immunosorbent assay(ELISA)method was used to detect TNF-a level and SP-A in serum,BCA kit and determination of inorganic phosphorus kit was used to detect total protein(TP)and total phospholipids(TPL)in bronchoalveolar lavage fluids.The Western-blot method was used to detect SP-A in lung tissues.Results:(1)There was no statistical significance for PaO2 level in the three groups of rats at 0h time(P >0.05).There was no significant difference for PaO2 level in group C between 3h time point and 0h time point.The PaO2 level in group OA at 1h,3h,5h time point was significantly lower than those at 0h time point,the differences were statistically significant(P < 0.01).Compared with group OA,PaO2 level was significantly increased in group C at 1h,3h,5h time point,the differences were statistically significant(P < 0.01).(2)Compared with group C,the lung wet / dry weight ratio(W/D value)in group OA was significantly higher,the differences were statistically significant(P < 0.01).Compared with group OA,the W/D value in group C was significantly lower at 1h,3h,5h time point,the differences were statistically significant(P < 0.01).(3)The alveolar structure was complete and there was no alveolar septum and hemorrhage in group C.The pulmonary capillary was expanded and congested,alveolar structure was damaged,alveolar septum was thickened,alveolar plasma was secreted,obvious changes of lung injury were appeared in group OA.There were some lung injury changes,however,compared with the group OA,lung injury degree was significantly reduced in group C.(4)The serum levels of TNF-a and SP-A were significantly increased in group OA than those in group C,the differences were statistically significant(P < 0.01).Compared with group OA,the serum levels of TNF-and SP-A were significantly lower in the group C at 1h,3h,5h,the differences were statistically significant(P < 0.01).(5)Compared with group C,the expression of TP and TPL in bronchoalveolar lavage fluids of rats was significantly reduced in group OA,the differences were statistically significant(P < 0.01).Compared with group OA,the expression of TP and TPL in bronchoalveolar lavage fluids was significantly higher in group C at 1h,3h,5h time point,the differences were statistically significant(P < 0.01).(6)Compared with group C,the expression of SP-A in lung tissue was significantly reduced in group OA,the differences were statistically significant(P < 0.01).Compared with group OA,the expression of SP-A in lung tissue was significantly higher in group C at 1h,3h,5h time point,the differences were statistically significant(P < 0.01).Conclusions: 1.The rat model of ALI/ARDS can be successfully replicated by tail vein injection of oleic acid.2.Injury of lungs and decrease of pulmonary surfactant exist in the early stage of ALI/ARDS.3.Ligustrazine can play a protect role in lung injury by alleviating inflammation reaction,and inhibiting the loss of pulmonary surfactant(mainly SP-A).