| Objective: To explore the intervention effect of different doses of baicalein on renal interstitial fibrosis induced by unilateral ureteral obstructionin and its possible mechanism of action.Methods: 1.30 healthy Wistar rats were randomly divided into sham operation group(n=12),operation group(n=18).The model of renal interstitial fibrosis was prepared after unilateral ureteral ligation.Then the pathological changes of the kidney were observed and recorded;2.Drug intervention: selected the successful model of time node as the time of drug intervention.40 healthy Wistar rats were randomly divided into two groups respectively,which included sham operation group and operation group.Then the operation group were randomly three groups,including model group,low dose group and high dose group of baicalein,10 rats were included in each group.The low dose group were treated with 2% baicalein solution of 50mg/kg/d,and high dose group were treated with solution 100mg/kg/d;model group and sham operation group were given daily 50mg/kg saline at the same time.At the end of the experiment,the change of body weight was recorded,rat serum and kidney tissues were collected,weight,serum creatinine,urea nitrogen,beta microglobulin(?2-MG)and retinol binding protein(RBP4),the pathological injury of renal tissue,the areas change of renal tubule and interstitial collagen fibers and alpha smooth muscle expression will be all recorded,and the changes of endoplasmic reticulum stress related proteins,such as CHOP and caspase-3 were detected by Western blotting.Results:(1)each group,s pathological changes were increased along with the time extending;renal tubular epithelial cell shedding and necrosis,tubular dilatation appeared at the third day after operation;renal interstitial tissues were increased with infiltration of mononuclear cells at seventh days;obvious renal tubular damage and renal interstitial fibrosis were found at tenth days.All of these showed that tenth days can be seen as the modeling time node;(2)Compared with model group,body weight of low dose group and high dose group increased significantly(P<0.01);kidney coefficient: there are statistically significant difference between high dose group and model group(P<0.01);Compared with model group,low dose group or high dosegroup,s urea nitrogen level were decreased,the difference between them was statistically significant(P<0.01);Compared with the model group,serum ?2-MG and RBP4 contents of low dose group or high dose group decreased(P<0.05),there is also difference between low dose group and high dose group(P<0.01);HE staining showed that the degeneration of renal tubular epithelial cells,edema of renal interstitial and infiltration of inflammatory cells in low dose group or high dose group were all reduced compared with model group;Masson staining showed that low dose group or high dose group,s collagen deposition were all decreased compared with the model group(P<0.01);immunohistochemistry showed that ?-SMA positive area in low dose group or high dose group were decreased compared with the model group,there is statistical significant difference between them(P<0.01);Western blot showed that CHOP,Caspase3 expression of low dose group or high dose group decreased compared with model group(P<0.01);Compared with low dose group,the decrease was more obvious in high dose group(P<0.05 or P<0.01).Conclusion:(1)baicalein could effectively intervene renal tubular and interstitial injury caused by ureteral ligation and protect renal function;(2)the effects of baicalein to delay the progress of renal interstitial fibrosis may be related to the inhibition of endoplasmic reticulum stress and apoptosis. |
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