Effect Of Tongfu Xiezhuo Formula On Renal Fibrosis And TGF-?1/p38MAPK Pathway In Rats With Chronic Kidney Disease

AimTaking Tongfu Xiezhuo formula as research subject,the research was proposed to evaluate its effects on uremic toxins,proteinuria,inflammatory factors,renal fibrosis and TGF-?1/p38MAPK pathway by building the model of chronic kidney disease rats,investigate its effects on renal function and renal fibrosis,explore the potential mechanism of Tongfu Xiezhuo formula on delaying renal fibrosis.MethodsPart 1:The effect of Tongfu Xiezhuo formula on protecting renal function in chronic kidney disease rats.Rats were divided randomly into a sham group,a model group,a niaoduqing group and a tongfu xiezhuo group.The model rats were administered adenine by means of intragastric administration,all rats were treated with predetermined medicine with a proper dose.After 8 weeks' treatment,the rat's urea nitrogen,creatinine,uric acid,indoxyl sulfate in serum and proteinuria were tested.Evaluate the effect of Tongfu Xiezhuo formula on protecting renal function in chronic kidney disease rats based on the experimental results,and explore the potential mechanism.Part 2:The effect of Tongfu Xiezhuo formula on renal fibrosis in chronic kidney disease rats.Rats were divided randomly into a sham group,a model group,a tongfu xiezhuo group and a rhubarb group.The model rats were administered adenine by means of intragastric administration,all rats were treated with predetermined medicine with a proper dose.After 8 weeks' treatment,the HE stain,Masson stain and immunohistochemistry were performed to observe the rat's renal morphological appearance,calculate the proportion of collagen fibers and examine the expression of a-SMA?Col-1 in the kidney.The effect of Tongfu Xiezhuo formula on renal fibrosis in chronic kidney disease rats was evaluated based on the experimental results.Part 3:The effect of Tongfu Xiezhuo formula ameliorates renal fibrosis by regulating TGF-?1/p3 8MAPK pathway.Rats were divided randomly into a sham group,a model group,a tongfu xiezhuo group and a rhubarb group.The model rats were administered adenine by means of intragastric administration,all rats were treated with predetermined medicine with a proper dose.After 8 weeks' treatment,the rat's urea nitrogen,creatinine,uric acid,Cystatin C,homocysteine,indoxyl sulfate,IL-6,TGF-?1 in serum,proteinuria and the expression of TGF-?1,p38MAPK,p-p38MAPK in kidney were tested.The mechanism of Tongfu Xiezhuo formula on ameliorating renal fibrosis in chronic kidney disease rats was evaluated based on the experimental results.ResultsPart 1:Compared with the model group,urea nitrogen,creatinine,uric acid in serum and proteinuria were all decreased in the tongfu xiezhuo group and the niaoduqing group(P<0.05),indoxyl sulfate was decreased in tongfu xiezhuo group(P<0.05).the level of urea nitrogen was decreased in tongfu xiezhuo group than the niaoduqing group(P<0.05).Part 2:Compared with the model group,the proportion of collagen fibers and the expression of a-SMA were decreased in the tongfu xiezhuo group and the rhubarb group(P<0.05),the expression of Col-I was decreased but the difference was not statistically significant(P>0.05).Part 3:Compared with the model group,urea nitrogen,creatinine,uric acid,Cystatin C,homocysteine,indoxyl sulfate,IL-6,TGF-?1 in serum,proteinuria were all decreased in the tongfu xiezhuo group(P<0.05),urea nitrogen,Cystatin C,IL-6 in serum,proteinuria were all decreased in the rhubarb group(P<0.05),the level of urea nitrogen and TGF-?1were lower in the tongfu xiezhuo group than the rhubarb group(P<0.05),evidently down-regulated TGF-?1 and p-p38MAPK expressions in the kidney in the tongfu xiezhuo and rhubarb groups(P<0.05).Conlusions(1)Tongfu Xiezhuo formula can protect CKD rat's renal function,reduce proteinuria and the accumulation of uremic toxins,delay the progression of the disease.(2)Tongfu Xiezhuo formula can ameliorate renal fibrosis by reduce renal collagen fiber ratio and a-SMA expression in the CKD rats.(3)Tongfu Xiezhuo formula can ameliorate renal fibrosis by regulating inflammatory factors reducing inflammation;and inhibiting activated TGF-?1/p3 8MAPK pathway.(4)Compared with rhubarb,Tongfu Xiezhuo formula has a better effect on protecting renal function,which exhibits the advantage of efficacy enhancing by combining traditional Chinese medicine.