The Experimental Study On Angiotensin-converting-enzyme-2(ACE2) And Renal Function In Obstructive Jaundice

In the study,the rats with obstructive jaundice(OJ)by bile duct ligation(BDL)were in the subjects.The following contents were done:(1)To observe the pathological change of kidney and expression of Angiotensin-Converting Enzyme 2(ACE2)m NRA in Kidney of rats,the serum bilirubin?creatinine of rats were also measured.(2)The rats with or without MLN-4760 or DIZE treatment,to study whether MLN-4760 or DIZE can change the expression of renin,ACE2,Angiotensin ?(Ang?),Angiotensin 1-7(Ang-(1-7))and aldosterone in the OJ rats.The potential relationship between the change of ACE2 and the change of renal function of rats with OJ were evaluated.(3)The rats with or without spironolactone treatment,to study whether spironolactone can change the expression of renin,ACE2,Angiotensin ?(Ang?),Angiotensin 1-7(Ang-(1-7))and aldosterone and ICAM-1 in the OJ rats.The potential relationship between the change of ACE2 and the change of renal function of rats with OJ were evaluated.1.The level of Angiotensin-Converting Enzyme 2(ACE2)m RNA in kidney of rats with obstructive jaundiceObjective:To study the level of ACE2 m RNA in kidney tissue and the serum total bilirubin(TBil)?creatinine(Scr)of rats with obstructive jaundice and primarily evaluate the relationship between the level of ACE2 and renal function.Methods:56 SD rats were randomly divided into two groups:Sham Operated group(SO,n=28)and Bile Duct Ligation group(BDL,n=28).The kidney tissue from each group were collceted at 3d,7d,10 d,14d after operation and ACE2 in kidney tissue were determined by fluorescent quantitation PCR and immunohistochemistry,the histopathological changes of the kidney tissue were observed after HE staining and Masson staining.At the same time,the blood from each group were collceted at 3d,7d,10 d,14d after operation and the serum bilirubin and creatinine were measured.Statistical analysis was performed using SPSS version 18.0 sotware.Data are given as mean± standard deviation(SD).Analysis of variance(ANOVA)was used to assess diferences between multiple groups.A p< 0.05 was considered statistically signiicant.The relationship between serum bilirubin,creatinine and the expression of kidney ACE2 were assessmented by Linear regression analysis.Results:(1)General conditions : the experimental rats without death during the experimental process.After bile duct ligation,the urine of the rats began to turn yellow by two days and the color of skin be gan to turn yellow by three to four days.The kidney observed in BDL group,which became obviously swelling,thickening and darkening by the time.(2)TBil and Scr 1evel were significantly higher in the OJ group than that of BDL group(P<0.0 5).(3)The express of ACE2 were significantly higher in 14 days in the OJ group than that of BDL group.(4)The correlation of the expression of kidney ACE2 and TBil is negative linear through regression,r=-0.516,the expression of kidney ACE2 had a negative linear correlation with Scr,r=-0.576.(5)The expressions of ACE2 in Kidney tissue immunohistochemical of the rats in OJ group were significantly lower than that in SO group,the expressions of ACE2 in OJ group were decrease with time extend.Conclusion: In OJ rats,there are obvious pathologic changes on kidney,the disturbance of liver and kidney function,and as the time prolong,the conditions become worse.The lower expressions of ACE2 in Kidney in OJ group were decrease with time extend.2.The effects of Diminazene Aceturate and MLN-4760 on the Expression of renin,ACE2,Ang?,Ang-(1-7)and aldosterone.in kidney of obstructive jaundice rats.Objective: To study whether Diminazene Aceturate and MLN-4760 can change the expression of renin,ACE2,Angiotensin ?(Ang?),Angiotensin 1-7(Ang-(1-7))and aldosterone in the OJ rats.The potential relationship between the change of ACE2,Ang?,Ang-(1-7)and aldosterone and the change of renal function of rats with OJ were evaluated.Methods: 56 SD rats were randomly divided into four groups:Sham Operated group(SO,n=14),,Bile Duct Ligation group(BDL,n=14),intervention by Diminazene Aceturate(DIZE)gruops(BDL+D,n=14)and intervention by MLN-4760 gruops(BDL+M,n=14).The kidney tissue from each group were collceted at 7d,14 d after operation and ACE2?renin?Ang II?Ang1-7?aldosterone in kidney tissue were determined by enzyme-linked immuno sorbent assay(ELISA),the histopathological changes of the kidney tissue were observed after HE staining.At the same time,the blood from each group were collceted at 7d,14 d after operation and the serum bilirubin and creatinine were measured.Results: After bile duct ligation,the serum Tbil and Scr 1evel were significantly higher in the OJ group and OJ+M group than that of BDL group and were not significantly different between BDL gruop?BDL+D gruop and BDL+M gruop.In kidney tissue were observed the express of aldosterone,renin,Ang II were significantly higher in the OJ group than that of BDL group,the express of Ang1-7 were significantly lower in the OJ group than that of BDL group.And DIZE,an ACE2 activator,intervention can partly reverse the above changes.MLN-4760 can intensified as an ACE2 inhibitors.HE staining staining also showed the kidney necrosis and inflammation,and fibrosis degree increase by the bile duct ligation,and DIZE ntervention in BDL rats can partly reverse the above changes.And MLN-4760 intervention can intensified these injury.Conclusion: Scr of BDL gruop were higher than SO group,and the aldosterone,renin,Ang II were significantly higher and the Ang1-7 were significantly lower in the OS group than that of BDL group.And the ACE2 activator DIZE can partly reverse the above changes,MLN-4760 intervention can intensified these injury as an ACE2 inhibitors.The levels of ACE2 maybe one of the reasons for the changes in renal function by obstructive jaundice.3.The effects of spironolactone on the Expression of renin,ACE2,Ang?,Ang-(1-7)and aldosterone.in kidney of obstructive jaundice rats.Objective: To study whether spironolactone can change the expression of renin,ACE2,Angiotensin ?(Ang?),Angiotensin 1-7(Ang-(1-7))and aldosterone in the OJ rats.The potential relationship between the change of ACE2,Ang?,Ang-(1-7)and aldosterone and the change of renal function of rats with OJ were evaluated.Methods: 42 SD rats were randomly divided into three groups:Sham Operated group(SO,n=14),Bile Duct Ligation group(BDL,n=14)and intervention by spironolactone gruops(BDL+S,n=14).The kidney tissue from each group were collceted at 7d,14 d after operation and ACE2?renin?Ang II?Ang-(1-7)?aldosterone in kidney tissue were determined by enzyme-linked immuno sorbent assay(ELISA),the histopathological changes of the kidney tissue were observed after HE staining and Masson staining.At the same time,the blood from each group were collceted at 7d,14 d after operation and the serum bilirubin and creatinine were measured.Results: After bile duct ligation,the serum Tbil and Scr 1evel were significantly higher in the OJ group than that of SO group and were not significantly different between BDL gruop and BDL+S gruop.In kidney tissue were observed the express of aldosterone,renin,Ang II and I-CAM1 were significantly higher in the OJ group than that of SO group,the express of ACE2,Ang1-7 were significantly lower in the OJ group than that of SO group.And spironolactone intervention can partly reverse the above changes.HE staining and Masson staining also showed the kidney necrosis and inflammation,and fibrosis degree increase by the bile duct ligation,and spironolactone intervention can partly reverse the above changes.Conclusion: Scr of BDL gruop were higher than SO group,and the aldosterone,renin,Ang II were significantly higher and the ACE2,Ang1-7 were significantly lower in the OS group than that of BDL group.there maybe one of the reasons for the changes in renal function by obstructive jaundice.And spironolactone intervention can partly reverse the above changes.