Effect Of Vitamin D On ACE2 And Vitamin D Receptor Expression Levels In Rats With LPS-induced Acute Lung Injury

Objective To observe the effect of vitamin D on angiotensin converting enzyme 2(ACE2)and vitamin D receptor(VDR)expression in Wister rat models of acute lung injury(ALI)induced by using lipopolysaccharide(LPS).To investigate the interaction between vitamin D and ACE2 in the pathogenesis of ALI/ARDS,and to provide a theoretical basis for the clinical diagnosis and treatment of ALI/ARDS.Methods The rat models of ALI induced by LPS were established by intravenous injection of LPS via tail vein.Thirty Wistar rats(class SPF,weight 200±20g)were randomly divided into 6 groups:(1)normal control group,intravenous injection of saline via tail vein;(2)LPS group;(3)calcitriol(25?g/kg)group;(4)LPS +calcitriol 1?g/kg group;(5)LPS +calcitriol 5?g/kg group;(6)LPS +calcitriol 25?g/kg group.All rats with the following experiment after intravenous injection of LPS via tail vein 24 h later.The changes of general condition(Respiratory status,mental status,activity situation,etc),lung pathology,lung wet/dry weight ratio changes of VDR mRNA and ACE2 mRNA expression and protein levels of VDR and ACE2 in rats were observed.Results 1.The model of acute lung injury was successfully made by LPS injection via tail vein.2.The pathological manifestations(rapid shallow breathing,listlessness,and bloody discharge was visible)in LPS group were serious,The Pathological manifestations and pathological changes of lung tissue of LPS +calcitriol 1?g/kg group and LPS +calcitriol 5?g/kg group and LPS +calcitriol 25?g/kg group were batter than LPS group.3.The lung wet/dry weight ratio of LPS +calcitriol 1?g/kg group and LPS +calcitriol 5?g/kg group and LPS +calcitriol 25?g/kg group were significantly decreased compared with LPS group(P<0.05),increased compared with calcitriol(25?g/kg)group(P<0.05).With the increase of vitamin D concentration,the ratio of dry / wet weight decreased gradually,but there was no significant difference between the three groups(P=0.110>0.05).4.The expression of VDR mRNA and ACE2 mRNA and protein levels of VDR and ACE2 in LPS group were significantly decreased compared with normal group and calcitriol(25?g/kg)group(P<0.05).5.The expression of VDR mRNA and ACE2 mRNA and protein levels of VDR and ACE2 in LPS +calcitriol 1?g/kg group and LPS +calcitriol 5?g/kg group and LPS +calcitriol 25?g/kg group were significantly increased compared with LPS group but significantly decreased compared with calcitriol(25?g/kg)group(P<0.05).6.The changes of expression of ACE2 mRNA and protein levels of ACE2 in LPS +calcitriol 1?g/kg group and LPS +calcitriol 5?g/kg group and LPS +calcitriol 25?g/kg group were statistically significant,but The changes of expression of VDR mRNA and protein levels of VDR has no statistically significant(P>0.05).Conclusions 1.The model of acute lung injury was successfully made by LPS injection via tail vein.2.The Pathological manifestations and pathological changes of lung tissue of LPS group worse than LPS +calcitriol 1?g/kg group and LPS +calcitriol 5?g/kg group and LPS +calcitriol 25?g/kg group,and calcitriol 25?g/kg group were better than three groups above.3.The lung wet/dry weight ratio of LPS group were significantly increased compared with LPS +calcitriol 1?g/kg group and LPS +calcitriol 5?g/kg group and LPS +calcitriol 25?g/kg group.With the increase of vitamin D concentration,the ratio of dry / wet weight decreased gradually,but there was no significant difference between the three groups(P>0.05);4.The expression of VDR mRNA and ACE2 mRNA and protein levels of VDR and ACE2 in LPS +calcitriol 1?g/kg group and LPS +calcitriol 5?g/kg group and LPS +calcitriol 25?g/kg group and calcitriol(25?g/kg)group were significantly increased compared with LPS group(P<0.05).but there were significantly decreased compared with calcitriol(25?g/kg)group(P<0.05).5.With the increase of vitamin D concentration,The expression of ACE2 mRNA and protein levels in LPS +calcitriol 1?g/kg group and LPS +calcitriol 5?g/kg group and LPS +calcitriol 25?g/kg group increased gradually,and there was statistically significant difference(P<0.05);The expression of VDR mRNA and protein levels was also increased,but the difference was not statistically significant(P>0.05).6.Vit D may play a protective role in the occurrence and development of ALI,which may be related to the expression of ACE2 and VDR in lung tissue of ALI rats.