Experimental Study Of Drugs On Renal Interstitial Fibrosis Of Uric Acid Nephropathy Rats

Objective To study the effect and possible mechanism of losartan, etoricoxib and colchicine on renal interstitial fibrosis of experimental uric acid nephropathy.Methods 60 male Wistar rats were randomly divided into normal group, model group, losartan group, etoricoxib group and colchicine group. The rats were fed with 10% yeast diet, and administered intragastrically with adenine (100mg/kg.d) for modeling. Losartan(20mg/kg.d), etoricoxib (10mg/kg.d) and colchicine(30ug/kg.d) were also given orally to evaluate their effect on experimental uric acid nephropathy. After 3 weeks and 5 weeks, six rats was randomly selected from each group, the angular venous blood and urine was collected for detecting uric acid(UA), creatinine(SCr), urea nitrogen(BUN), corrected creatinine clearance rate and left renal weight index, kidneys were obtained after executed to study renal histological changes by Haematoxylin & eosin (HE) and Masson staining, and the expression of transforming growth factor-β1 (TGF-β1), plasminogen activator inhibitor-1(PAI-1)and interleukin-1β(IL-1β) were analyzed by immunohistochemical staining.Results①Compared with normal group, model group after 3 weeks and 5 weeks showed much higher UA, SCr, BUN and lower corrected creatinine clearance rate(P<0.01 or P<0.05). Compared with model group, losartan group and etoricoxib group showed significantly lower SCr and left renal weight index(P<0.05) after 3 weeks and 5 weeks, but UA and BUN didn t change much; colchicine goup had no significantly changed UA, SCr, BUN and left renal weight index (P>0.05).②Compared with normal group, model group after 3 weeks and 5 weeks showed much more interstitial collagen deposition and TGF-β1, PAI-1, IL-1B expression(P<0.01). Compared with model group, losartan group and etoricoxib group showed significantly lower TGF-β1, PAI-1 and IL-1B expression, along with interstitial collagen deposition after 3 weeks and 5 weeks (P<0.05 or P<0.01); colchicine group showed improved collagen deposition, TGF-β1 and IL-1βexpression only after 5 weeks(P<0.05), while PAI-1 didn’t change much (P>0.05). The difference of TGF-β1 expression between losartan group and colchicine group was no statistically ignificant (P<.05).Conclusions①Experimental uric acid nephropathy can be modeled by 10% yeast diet and adenine 100mg/kg.d. IL-1β, TGF-B1 and PAI-1 increase and participate in uric acid nephropathy.②Losartan, etoricoxib can improved renal fuction and interstitial fibrosis of uric acid nephropathy, associated with downregulation of IL-1β, TGF-β1 and PAI-1.③Colchicine can also retard the progress of its renal interstitial fibrosis by downregulating IL-1βand TGF-β1.