Effect Of Curcumin On Renal Expression Of Transforming Growth Factor-?1 And Nuclear Transcription Factor-kappa B In Hyperuricemia Rats

Background and ObjectivesHyperuricemia(HUA)is a metabolic disease which can be caused by increasing synthesis of uric acid and/or reducing excretion of uric acid.In recent years,with the improvement of living standards and dietary changes,the prevalence of hyperuricemia has been increasing year by year,presenting a trend of youthfulness.Hyperuricemia can cause glomerulosclerosis through inflammatory reactions,oxidative stress and so on.Many studies have shown that hyperuricemia cause renal damage by upgrading expression of transcription factor-?1(TGF-?1),which is important in renal interstitial fibrosis.Hyperuricemia can upgrade expression of transcription factor-?1(TGF-?1)which induces epithelial-mesenchymal transition(EMT).Nuclear transcription factor-?B(NF-?B)is a nuclear transcription factor.With multi-directional regulation it can regulate the expression of several cytokines,chemokines,and protein genes which cause symptoms of inflammation,oxidative stress,immune response,and cell proliferation participating the progress of kidney disease.Curcumin is a plant polyphenol which is extracted from turmeric and has powerful anti-inflammatory and anti-oxidant effects.Curcumin can reducing urinary protein and kidney fibrosis by reducing the oxidative stress,inflammatory reaction and other processes,which is playing a protective role in the development of chronic kidney disease.Recent years,there are much more attention to the renal protection of the curcumin.But there is few research on the protective effect of hyperuricemia.In our study,through established the rat model of hyperuricemia we can observe the expression of TGF-?1 and NF-?B in the renal tissue of hyperuricemia rats and explore the possible mechanism of curcumin's renal protective effect.Subjects and Materials1.According to the random number table,normal male Sprague-Dawley rats were divided into normal control group(NC),hyperuricemia group(OP group)and curcumin group(OC group);OP and OC groups were intragastric potassium oxonate(OA)to establishment the rat model of hyperuricemia.After the model was successfully established,curcumin was intragastric to the OC group for 8 weeks.Serum uric acid levels(SUA)were measured at 0,4 and 12 weeks in each group.At the 12 weeks of treatment,rats were monitored for Serum creatinine(Scr),urea nitrogen(BUN),24-hour total urine protein,and serum cystatin C(Cys-C)level and so on.2.HE and Masson staining were performed to observe the pathological changes of kidneys.Immunohistochemistry were used to observe the expression and distribution of TGF-?1 and NF-?B on the renal tissues of hyperuricemia rats.Results1.Compared with NC group,SUA levels in OP group and OC group increased significantly in the fourth week(P=0.000),and the difference was statisticallysignificant.There was no significant difference in SUA level between OC group and OP group(P=0.056)Compared with the NC group,there was a statistically significant difference in the SUA level between the OP group and the OC group at the twelfth week(P=0.000);there was no significant difference between the OC group and the OP group in the SUA level(P=0.641)2.Compared with NC group,The Scr,BUN,24-hour urinary protein and Cys-C levels were significantly higher in the hyperuricemia rats than those in the normal control rats(P = 0.000),and those biochemical indicators in the OC group were also significantly higher compared with the normal group(P =0.000).The Scr,BUN,24-hour urinary protein,and Cys-C in the curcumin treated group were obviously lower than those in the hyperuricemia rats(P= 0.043 P= 0.002 P=0.000P=0.002).3.The pathology in kidney of normal rats showed that the structure of glomerular and tubular is clear,the thickness of the basement membrane is uniform and the capillary lumens is well opened.There is no inflammatory cell infiltration as well as no proliferation in fibrotic tissue in the renal interstation;Through HE and Masson staining we can observe that in the hyperuricemia rats,the structure of glomerular is clear,but part of renal tubule epitheliums were swelling and a large number of inflammatory cell infiltrated into renal.After intervention of the curcumin,OC group pathological damage are significantly improved compared with the hyperuricemia group.4.Immunohistochemistry noted that TGF-?1 and NF-?B is expressed not only in the renal tubule but also in the glomerular.The positive expression of TGF-?1 and NF-?B showed brownish yellow or dark brown by Immunohistochemically SP.The expression of TGF-?1 and NF-?B was significantly increased in the OP and OC rats compared with those in the normal group(P =0.000).But is was decreased in OC rats compared with OP rats.Conclusions1.The expression of TGF-?1 and NF-?B significantly increased in kidneytissue of hyperuricemia rats,suggesting that TGF-?1 and NF-?B are involved in the development of renal injury in hyperuricemia.2.Hyperuricemia rats which were treatment with curcumin,serum creatinine,urea nitrogen,cytostatic C,24-hour urinary protein quantification were significantly decreased,and TGF-?1,NF-?B expression was decreased,suggesting that curcumin play a protective role in the kidney of hyperuricemia rats.The renal protective effect of renal damage in rats is associated with its mechanism of down-regulation of TGF-?1 and NF-?B expression.