The Study Of The Relief Effect Of Levamlodipine Besylate On Enhanced Renal Damnification To Residual Renal Function By Guanidinopropionic Acid

Objective:This study is focused on the relief effect of levamlodipine besylate to enhancedrenal damnification by guanidinopropionic acid, and this effect of alleviation of therenal fibrosis in CRF rats induced by5/6nephronectomy.Methods:Rats randomly divided into group A、B、C、D. the group A were as sham-operatedgroup, and the rest three groups. The surger in the rest three groups (CRF modelgroup B, GPA group C and GPA-levamlodipine besylate group D)were5/6nephronectomy.For group A and group B,, we give intraperitoneal injection of salineand insert the physiological saline to the stomach. For the group C，Based on thesame amount of saline intragastric gavage,we were administered GPA byintraperitoneal injection with5mg/(kg d);rats in group D were administered with5mg/(kg d) GPA by intraperitoneal injection and0.625mg/(kg d) levamlodipinebesylate by intragastric gavage.After operation,to measure the Urine protein (Up) atthe4th and6th weekend, and to measure serum BUN, serum creatinine and to observethe renal pathology changes in10th weekend(HE and PAS). In residuary renal tissue，by the immunohistochemistry to measure expression of the collagen-Ⅰ, smad2/3,smad7. In the residual renal tissue by TUNEL, there were observed the apoptosis ofintrinsic cell..Results:1.24-hour Urine protein:Results Compared with group A, the Up level in thegroup B、C、D in rats increased, and it increased significantly in group C(P<0.01),reached3.67times. there was a significant increase of the4th and6th week’ Up levelin the group C rats compared with the group B(P<0.05), between groups C and D,haven’t statistically patency difference at4and6weeks after operation (P>0.05).2. Serum BUN, Serum creatinine：Results Compared with group A, the bun andscr level in the group B、C、D in rats increased, and it increased significantly in groupC(P<0.01), as high as5.45and3.93times. compared with the group B, there was asignificant increase of the10th week’ bun and scr level in the group C(P<0.01).There were distinct differences between the BUN level in the group C and D(P<0.05),but the SCR level not so obvious(P>0.05)。3. Pathological examination by PAS staining： Except the group A,glomerulosclerosis，mesangial hyperplasia and extension in different degrees werefound in other groups with remnant renal tissues of5/6Nephrectomy rats. Incomparision with the group C and the group D, glomerulosclerosis，mesangialhyperplasia and extension of the group A were obviously more serious; to evaluationGSI score, compared with Group C, the score of GSI is distinct increased in Group D(P<0.05);to evaluation the score of renal tubular-interstitium injury, compared withGroup C, the score of GSI is significantly increased in Group D (P<0.05).4.col-I, smad2/3and smad7in residual renal tissue: in remnant renal tissues of5/6Nephrectomy rats, showed that the col-I and smad2/3’s expression level hadobvious difference than group B (P<0.01),and the group C was distinct higher thanthe group D (P<0.01). for the smad7,the expression level of in group B was markedlylower than the group A (P<0.01), and the expression level of group C was significatilylower than group D(P<0.01),However, the expression level of the group D wasdistinct higher than group C ‘s(P<0.01)5.Apoptotic index：The group B’s apoptosis level was obviously higher than thatof group A; and group C’s apoptosis level was significatily higher than group B’s(P<0.01)， There were significances in statistics. Nevertheless, group D’s wasapparently lower than group C’s (P<0.05).Conclutions:1. GPA increase the related protein expression of col-I, smad2/3for acceleratingin fibrosis kidney tissue and lower the protein expression of smad7for depressingfibrosis at the same time. 2. GPA can stimulate the apoptosis of intrinsic cells in the kidney of rats withCRF.3. levamlodipine besylate may relieve the apoptosis of intrinsic cells and chronicfibrosis in the kidney of rats with chronic renal failure,which involves the inhibitoryeffect of levamlodipine besylate on the expression of col-I, smad2/3and stimulativethe expression of smad7.