Preliminary Study On The Effect Of High Density Lipoprotein On Pulmonary Vascular Permeability In Mice With Acute Respiratory Distress Syndrome

Objective: By detecting the oxidation sites of apoA-I in Acute Respiratory Distress Syndrome(ARDS)patients and normal persons in High Density Lipoprotein(HDL),to investigate the effect of two different HDL on pulmonary vascular permeability in ARDS mice.Methods:(1)Patients with ARDS caused by sepsis were enrolled in the study,the HDL extracted from their venous plasma was used as the abnormal HDL group.And the normal healthy persons matched by the gender and age were enrolled in the same group,the HDL extracted from their venous plasma was used as the normal HDL group.Then was the detection of oxidation sites of apoA-I in normal HDL and abnormal HDL by mass spectrometry.(2)Mice were divided into three groups: PBS group,normal HDL group and abnormal HDL group.PBS,normal HDL(50mg/kg)and abnormal HDL(50mg/kg)were injected into the mice through tail vein,and the mouse models of ARDS were established by cecal ligation puncture(50% cecal ligation).Then Evans blue dye(50mg/kg)were injected into the three groups of ARDS mice by tail vein.Three groups of mouse alveolar lavage fluid were taken 4hours later and the light density of alveolar lavage solution were detected at 630 nm with Microplate Reader.The higher value of optical density,indicating more Evans blue permeated respiratory membrane,showed that mice pulmonary vascular permeability is higher.Results:(1)The oxidation sites of HDL/apoA-I in ARDS patients and normal groupswere mainly concentrated in M86(eighty-sixth methionine),M112(112nd methionine),M148(148th methionine),W50(fiftieth tryptophan),W72(seventy-second tryptophan)and W108(108th tryptophan).The proportion of M86 oxidation was higher in the normal group(P<0.05),the proportion of W50 oxidation in the ARDS group was higher(P<0.001),and the difference between the two groups was statistically significant.While the proportion of M112,M148,W72 and W108 oxidation had no significant difference(P>0.05).(2)Animal experiments showed that the pulmonary vascular permeability of ARDS mice was different in the three groups.Compared with the PBS group,the optical density of alveolar lavage fluid at 630 nm in the normal HDL group was significantly lower,and the difference between two groups was statistically significant(P<0.05);while there was no significant difference in the abnormal HDL group.And compared with the abnormal HDL group,the optical density of alveolar lavage fluid at 630 nm in the normal HDL group was significantly lower,the difference between two groups was statistically significant(P<0.05).Conclusion:(1)There were oxidation difference in HDL/apoA-I between the ARDS patients and the normal group.(2)Normal HDL can reduce pulmonary vascular permeability in ARDS mice and have protective effect during the pathogenesis of ARDS,while abnormal HDL has no this effect.