Therapeutic Effects of Breviscapine Tablets on Renal Fibrosis Induced by Adenine in Rats Based on Notch Signaling Pathway
Objective:To study the therapeutic effects of breviscapine tablets on renal fibrosis in rats and explore its potential mechanisms.Meth-ods:SD rats were divided into the following groups:blank control,model control,colchicine group(0.45 mg/kg),and breviscapine tablet groups(5.5,11,and 22 mg/kg).The rat model of renal fibrosis was established by intragastric administration of adenine,the rats were intra-gastrically administered with breviscapine tablet suspension once a day,for 30 days.Two hours after the final administration,the rats were an-esthetized,and their blood samples were collected to measure the content of serum creatinine(Scr)and blood urea nitrogen(BUN).The kid-ney was collected to determine the kidney index,and the pathologic changes of renal tissue were observed through hematoxylin-eosin(HE)staining and Masson's staining.Immunohistochemistry and RT-PCR were performed to measure the protein and mRNA expressions of Notch1,Jagged,and Hes1 in renal tissue.Results:Compared with the blank control group,the model control group showed a significant increase in kidney index,BUN,and Scr content(P＜0.01),while the BUN/Scr ratio decreased greatly(P＜0.05).According to HE staining results of re-nal tissue,disrupted renal tubular structures and infiltration of inflammatory cells were observed.Masson's staining result showed that the blue positive staining area was increased,and the protein and mRNA expression levels of Notch1,Jagged 1,and Hes1 were significantly up-regulated(P＜0.01).Compared with the model control group,the kidney index and the content of BUN and Scr were significantly decreased in brevis-capine tablet groups(P＜0.05),and the BUN/Scr ratio significantly increased(P＜0.01).Furthermore,the severity of renal fibrosis was im-proved according to the pathologic changes of the kidney.The protein and mRNA expression levels of Notch1,Jagged1,and Hes1 in the kidney were down-regulated significantly(P＜0.01).Conclusions:Breviscapine tablets can alleviate adenine-induced renal functional injury in rats and improve renal interstitial fibrosis to a certain extent.The underlying mechanism may involve the inhibition of the Notch signaling pathway.
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