| Object: Acute kidney injury(AKI) is a common critical and severe disease in clinic setting.If not given early diagnosis and therapy,it's often developed to an irreversible kidney damage.Many etiological factor involved in the pathophysiology process of AKI.The pathogenesis of AKI is highly complex and only poorly understood up to days. Nowadays,despite of the advance in medical technology,the morbidity and mortality of AKI has not decreased significantly.So how to prevent and treat early AKI is an important topic in basic and clinical nephrologist.Adhesion molecules are transmembrane glycoproteins that expressed on cell surface or extracellular matrix,which have the function of adhesive attraction to mediate interactions between cell-cell or cell-matrix.They induced inflammation reaction and involved in the occurrence of AKI.Renal tubular epithelial cells sublethal damage and lose cell polarity play an important role in AKI.The abnormity expression of adhension molecules and membrane protein in cell suface or matrix aggravate the kidney damage.Therefore,we investigate the expression of adhesion molecules in renal tissue to reveal the pathogenesy of AKI all the better. ICAM-1 and P-selectin are members of IGSF and selectins family of adhension molecules.They are expressed little in normal renal.With the activating of TNF-α,IL-1,IFN-γ,the expression of ICAM-1 and P-selectin are increased.They induce leucocyte adhere to vascular endothelial cell and play an important role in AKI.E-cadherin is the member of cadherins family.E-cadherin andβ-catenin compose of adherens junction of renal tubular epithelium,which is relate to tubular epithelium polarity.They play an important role in maintaining the normal structure of renal tissue.Renal tubular epithelium loss polarity and epithelial cells dislodged from the basemet membrance to the tubule lumina may relevant to them.Ixeris Sonchifolia Hance mainly consist of adenosine and flavone.They have the function of inhibiting oxygen free radical,preventing and curring ischemia or ischemia/reperfusion injury,and improving the renal microcirculation.To investigate the mechanism and search the method to preventing AKI,an experimental animal model was developed by injecting glycrol into the muscle of rats to simulate rhabdomyolysis induced AKI.The expression of P-selectin,ICAM-1,E-cadherin andβ-catenin in renal tissue were observed by immunohistochemical method in normal and AKI rats.At the same time,we observed the protective effect of Ixeris Sonchifolia Hance on AKI induced by glycerol in rats.Methods: 1.Forty-five male Sprague-Dawley rats were randomly divided into control group(CN,n=15),acute kidney injury group(AKI,n=15) and ixeris sonchifolis group(IS,n=15).On deferent injection times every group divided into three subgroups: 1h,6h and 24h.The rats of control group received 10ml/kg of 0.9% Normal Saline by intramuscular injection.The rats of IS group received 20g/kg of Ixeris Sonchifolia Hance by intraperitoneal injection 15 minutes before rceived 10ml/kg of 50% glycerol by intramuscular injection. 2.An experimental AKI model was developed by intramuscular injection of 50% glycerol at the dose of 10ml/Kg in rats. 3.Blood samples were collected for assay of biochemical parameters.Then,kidneys were removed,putting them into 4℃4%paraformaldehyde for paraffin slice. 4.The levels of Scr,BUN and CK were measured by biochemistry analyzer.The renal tissue morphological changes were observed by light microscope.The expression of P-selectin, ICAM-1,E-cadherin andβ-catenin in renal tissue were observed by Immunohistochemical staining and image analysis.Result: 1.The serum biochemical parameters increased remarkably after glycerol injection.The levels of Scr and CK increased in AKI 1h group(P<0.05).The levels of Scr,BUN and CK was significantly increased in AKI 6h group compared with control group(P<0.01),and increased predominantly in AKI 24h group(P<0.01).The levels of Scr,BUN and CK decrease remarkably in IS groups compared with AKI groups(P<0.05 or P<0.01),but increase compared with control groups(P<0.01). 2.The pathology of renal tissue was no changes in control rats.Some tubules appear casts in the lumen in AKI 1h rats,and some proximal tubule epithelial cells appear intumesce.There were more casts in the lumina in AKI 6h rats.The epithelial cells of tubule appear hyaline degeneration,and the renal interstitium are congested.We observed acute tubule necrosis in AKI 24h rats.The extent of degeneration and necrosis of tubule epithelial cells in IS rats was lighter than that of AKI rats. 3.It was only little expression of P-selectin and ICAM-1 in renal tissue of control rats.The expression of P-selectin and ICAM-1 were significant increased at 1 hour after glycerol injection in AKI rats compared with control group(P<0.05),and remain increased in 6h and 24h subgroup(P<0.01).The expression of P-selectin and ICAM-1 were decreased in IS groups compared with AKI groups(P<0.05 or P<0.01). 4.E-cadherin andβ-catenin were expressed in the memberance of renal tubular epithelial cell in control groups.The expression of E-cadherin was decreased significantly at 1 hour after glycerol injection in AKI rats compared with control group(P<0.05),and decreased remarkably in 6h and 24h subgroups(P<0.01).The expression ofβ-catenin was decreased significantly at 6 hours after glycerol injection in AKI rats(P<0.05), and decreased significantly in 24h subgroup (P<0.01).The expression of E-cadherin andβ-catenin were increased at 24 hours after glycerol injection in IS group compared with AKI group(P<0.05).Conclusion: 1.The structure and function of renal tissue changed remarkably in rats after intramuscular injection of glycerol.The levels of Scr,BUN and CK were increased significantly.The renal glomerulus were congestion.Tubule epithelial cells appear intumesce,dislodged from the basement membrane or necrosis. There were protein casts in the lumina of tubules. These results suggest that the acute kidney injury was induced by glycerol of intramuscular injection which may simulate rhabdomyolysis induced AKI. 2.The expression of P-seletin and ICAM-1 were increased in rats after injection of glycerol. They promoted inflammatory reaction and involved in AKI.It may be one of the important pathogenesis of AKI. 3.The expression of E-cadherin andβ-catenin were distributed abnormally and reduced in renal tissue of AKI rats.The injuried epithelial cells loss polarity and dislodged from the basement membrance to the lumina.These luminal contents enhance the obstruction of renal tubular.E-cadherin andβ-catenin may play an important role in the development of AKI induced by glcerol. 4.Ixeris Sonchifolia Hance downregulation the expression of ICAM-1 and P-selectin,and upregulation the expression of E-cadherin andβ-catenin in renal tissue of rats with AKI.It relieved the injury of kidney and improved the renal function.Thus,we observed the protective effect of Ixeris Sonchifolia Hance in AKI.
|
PDF Full Text Request