Effect Of Yiqi Tongyang Decoction On Tubulointerstitial Fibrosis In Unilateral Ureteral Obstruction Rats And Its Mechanism

Objective: Renal interstitial fibrosis is the common pathway and main pathological basis for the development of chronic kidney disease to end stage renal disease,The current treatment measures have a pharmacological effect against renal fibrosis to a certain extent,but the overall therapeutic effect is not very satisfactory,and it cannot prevent its progression to endstage renal disease.This study was to investigate the effect of Yiqi Tongyang Decoction on tubulointerstitial fibrosis in unilateral ureteral obstruction rats and its mechanism.Methods: Unilateral ureteral obstruction(UUO)model was established in healthy male SD rats.The experiment was divided into two parts:Part I: Effect of Yiqi Tongyang Decoction on Renal Function and Structure in UUO RatsSD rats were randomized divided into four groups: sham operation(Sham)group,model(UUO)group,Chinese medicine(UUO+H)group and Western medicine(UUO+Y)group,with 10 rats in each group.Excluding the sham operation group,UUO models were established in the others.Then the UUO+Y group was given enalapril 0.18 mg/m L by gavage,the UUO+H group was given Yiqi Tongyang Decoction concentrated liquid 1.188 g/m L by gavage,and the other groups were given the same amount of normal saline once a day.After 14 days,serum was collected for detecting the levels of SCr and BUN.Then the rats were killed for taking the renal tissue and conducting HE and Masson staining to observe the morphological changes of kidneys and the degree of interstitial fibrosis.Part II The mechanism of Yiqi Tongyang Decoction Delays Renal Interstitial Fibrosis in UUO RatsThe kidney tissue obtained in the first experiment was divided into three parts.The expression of TGF-?1 and FN in kidney tissue was detected by IHC method in one part,and the expression of Smad7 protein and its m RNA in kidney tissue was detected by Western blot and RT-PCR in the other two parts.Results:1.Blood biochemical indicators showed that compared with Sham group,serum SCr and BUN were significantly increased in UUO group(P < 0.05);Compared with UUO group,serum SCr and BUN were significantly decreased in UUO+H group and UUO+Y group(P < 0.05).And there was no significant difference between the UUO+H group and the UUO+Y group.2.The kidneys of rats in Sham group were normal in appearance,glossy,reddish brown,regular in shape and flexible in texture.The kidneys of obstructive side of rats in the three model groups were enlarged in different degrees,irregular in shape,thinned in renal cortex and hydronephrosis.3.HE and Masson staining results showed that the kidney tissue of Sham group was normal,the size of glomerulus and tubule was normal,the renal tubules arranged neatly and compactly,there was no tubular dilatation,and a small amount of blue collagen fibers deposited in the renal interstitium.The kidneys of rats in Sham group were normal in appearance,glossy,reddish brown,regular in shape and flexible in texture.In UUO group,the kidneys showed atrophy of renal tubules and dilatation of lumen.At the same time,renal interstitial edema and a large number of inflammatory cells infiltrated.There was a large amount of blue collagen deposition in renal interstitium and tubules.Inflammatory cell infiltration,tubular dilatation and interstitial collagen deposition in obstructive kidney of UUO+H group and UUO+Y group were less than those of UUO group.TIS showed that the TIS of UUO group was significantly higher than that of Sham group(P < 0.05).However,compared with UUO group,TIS of UUO+H group and UUO+Y group were significantly lower(P < 0.05),but there was no significant difference between UUO+H group and UUO+Y group.4.The results of IHC showed that TGF-?1 was mainly expressed in renal tubular epithelial cells in normal renal tissues,but not in glomeruli,and the expression of FN was mainly located in the mesangial area.The expression of TGF-?1 and FN in Sham group was weaker and lightly colored;the expression of TGF-?1 and FN in UUO group was significantly higher than that in Sham group,showing brown granular deposits and deep coloration,with significant difference in gray value between the two groups(P < 0.05);the expression intensity of TGF-?1 and FN in UUO+H and UUO+Y group was between Sham group and UUO group,and compared with UUO group,both Chinese and Western medicine treatments could reduce the expression of TGF-?1 and FN.The expression of TGF-?1 and FN was not significantly different between UUO+H and UUO+Y groups(P < 0.05).5.Western blot results showed that compared with Sham group,the expression of Smad7 protein decreased in other groups(P < 0.05);compared with UUO group,the expression of Smad7 protein increased in UUO+H group and UUO+Y group(P < 0.05).6.RT-PCR results showed that compared with Sham group,the m RNA expression of Smad7 decreased in other groups(P < 0.05);compared with UUO group,the m RNA expression of Smad7 increased in UUO+H group and UUO+Y group(P < 0.05).Conclusion:1.Yiqi Tongyang Decoction can improve renal function in UUO rats.2.Yiqi Tongyang Decoction can alleviate the pathological damage of kidney and the degree of renal interstitial fibrosis in rats.3.Yiqi Tongyang Decoction can down-regulate the expression of FN and alleviate the accumulation of extracellular matrix.4.Yiqi Tongyang Decoction may delay the progress of renal interstitial fibrosis by upregulating the expression of Smad7 protein and inhibiting the high expression of TGF-?1 in renal tissue of UUO rats.