The Effect Of Endotoxemia On Lung And Kidney Function And Angiotensin Ⅱ And Its Receptors In Rats

Objective: This research established animal models of endotoxin induced acute lunginjury and acute kidney injury.Then observed the changes of lung and renal function,the changes of AngII and its receptors in the lung and kidney,and discussed themechanism of lung-kidney crosstalk in MODS,in order to provide experimental dataand theoretical basis for the prevention and cure MODS in clinical.Methods:2months of age male Wistar rats receive tail intravenous injection oflipopolysaccharide to build a model of sepsis.All rats are randomly divided intonormal group and lipopolysaccharide group (LPS group).Six rats are executed at2ndhour,6th hour,12th hour,24th hour after injected saline or lipopolysacchariderespectively. Each group’s blood is collected. Lung and renal samples are collected atthe meantime. Then complete the following tests:(1)Measure the lung wet/dry weightratio and observe lung pathological to realize lung injury degree.(2) Measure the levelof serum creatinine and urea and observe renal pathological to realize renal injurydegree.(3)Application of radiation immunoassay to detect AngII concentrationchanges in plasma,lung and renal tissues.(4)Using Immunochemical staining andWestern bolt measure expression of AT1R and AT2R in lung and renal.(5)Theconcentration of TNF-a in serum are measured by enzyme-linked immunosorbentassay (ELISA).Result: Compared with control group,rats in endotoxemia group at each time point:(1)The lung function appear decline at different degree,lung wet/dry weight ratioincreased,it was significant at2nd hour,6th hour,12th hour(P<0.05).Lung pathology showed different degree of inflammatory cell infiltration,hemorrhage,edema,andtransparent membrane formation.(2)The level of serum creatinine and urea areincreased significantly in each time point (P<0.05).Kidney tissue pathology showeddifferent degrees of glomerular neutrophil infiltration, renal tubular epithelial cellswelling, vacuoles degeneration, necrosis and shedding.(3)The content of plasmaAngII increased significantly at2nd hour,6th hour(P<0.05),but began to decline after6th hour. Levels of AngII in lung and kidney tissues were increased significantly ateach time point (P<0.05). AngII in three kinds of organization were significantlypositively related to lung and renal function injury (P=0.000).(4) Level of AT1Rprotein expression in the lung and kidney decreased obviously in each timepoint(P<0.05),and negatively correlated with lung and kidney damage(P=0.000).Level of AT2R protein expression in the lung increased significantly in each timepoint (P<0.05), and increased significantly only at12nd hour and24th hour forkidney AT2R protein (P<0.05). AT2R was significantly positively related to lung andrenal function injury(P=0.000).(5)The level of serum inflammatory factors TNF-aincreased significantly at2nd hour,6th hour,12th hour(P<0.05),and declined after12thhour,and three kinds of AngII was significantly positively related to TNF-alevel(P=0.000).Conclusions:(1)In the early stage of sepsis,the lung and renal function of ratdamaged in different degree.(2)RAS system components in endotoxin rats werechanged,the changes of AngII and ATR were correlation with lung and kidney injury.(3)AngII may act as an inflammatory factor involved in the lung and kidney injuryinduced by LPS in endotoxemia.