The Study Of The Inhibition Effect Of Probuc On Increased Renal Impairment To Residual Renal Function By Methylguanidine

ObjectiveTo study the inhibition effect of probucol on increased renal impairment bymethylguanidine, and its effect of prevention of the renal fibrosis in chronic renalfailure rats induced by5/6nephronectomy.MethodsRats were randomly assigned to sham operation group A and operation group (B,C, D). Rats in operation group were prepared with5/6nephronectomy, then rats weredevided into three groups: control group B, methylguanidine group C andmethylguanidine-probucol group D. Rats in group A which is the normal control group,were given the same amount of saline by intraperitoneal injection and intragastric gavage;rats in group B were given the same amount of saline by intraperitoneal injection andintragastric gavage; rats in group C were administered with4mg kg-1dmethylguanidine by intraperitoneal injection at first, then were given the same amount ofsaline by intragastric gavage; rats in group D were administered with4mg kg-1dmethylguanidine by intraperitoneal injection and500mg kg-1d probucol by intragastricgavage;. Urine protein (Up) were measured at the4th and6th week after operation,and serum BUN, creatinine (Cr) were measured at10th week following operation.Renal pathology changes were evaluated at10th week. Immunohistochemistry wereused to examine the expression of transforming growth factor(TGF-β1), connectivetissue growth factor(CTGF) and fibronectin (FN) in renal tissue. The apoptosis of cellin the renal tissue were abserved by TUNEL.Results1.24-hour Urine protein at the4th and6th week after operation: group B was significantly higher than group A (P<0.05); group C was significatily higher thangroup B(P<0.05); group D was significatily lower than group C(P<0.05).2. Serum BUN, creatinine (Cr) at10th week following operation：group B wassignificantly higher than group A (P<0.05); group C was significatily higher thangroup B(P<0.05); group D was significatily lower than group C(P<0.05).3. Pathological examination by HE staining: the volume of glomerular in groupB was larger than group A, and glomerular mesangial cells and matrix proliferationappared; the volume of glomerular in group C was larger than group B, andglomerular mesangial cells and matrix proliferation became more severe; the volumeof glomerular in group D was smaller than group C, and glomerular mesangial cellsand matrix proliferation mitigated.4. TGF-β1, CTGF and FN in immunohistochemistry: group B was significantlyhigher than group A (P<0.05);group C was significatily higher than group B(P<0.05);group D was significatily lower than group C(P<0.05).5. Apoptotic index showed in TUNEL: group B was significantly higher thangroup A (P<0.05); group C was significatily higher than group B(P<0.05); group Dwas significatily lower than group C(P<0.05).Conclutions1. Methylguanidine can stimulate the expression of fibrosis-related factor(TGF-beta1, CTGF and FN) in the kidney of rats with chronic renal failure.2. Methylguanidine can stimulate the apoptosis of intrinsic cells in the kidney ofrats with chronic renal failure.3.Probucol has the inhibition effect to the apoptosis of cells in the kidney ratswith chronic renal failure and the expression of fibrosis-related factor (TGF-β1, CTGFand FN).