白芍总苷对大鼠柔红霉素肾病的作用及机制

Effect and mechanism of total glucosides of Paeony in rats with daunorubicin-induced nephropathy

目的探讨白芍总苷(TGP)对大鼠柔红霉素(DRB)肾病的治疗作用及干预机制。方法 16只雄性SD大鼠尾静脉注射DRB 1mg/100g建立肾病模型后均分为两组:TGP组给予TGP灌胃,每日10mg/100g,连续8周;DRB组作为模型对照。另取正常大鼠8只为空白对照(CON)组。DRB组和CON组予等量生理盐水灌胃。灌胃8周后,测定血清总蛋白(TP)、总胆固醇(TC)、血清肌酐(SCr)、血尿素氮(BUN)及24-h尿蛋白定量;HE染色观察肾脏病理改变,RT-PCR检测JAK2和STAT3 mRNA相对表达量,Western blot检测磷酸化JAK2(p-JAK2)和p-STAT3蛋白相对表达量。结果 DRB组和TGP组TP均低于CON组,而TC、SCr、BUN及24-h尿蛋白定量均高于CON组(P<0.01);TGP组TP高于DRB组,而TC、SCr、BUN及24-h尿蛋白定量低于DRB组(P<0.01)。DRB组和TGP组的JAK2、STAT3mRNA和p-JAK2、p-STAT3蛋白相对表达量均高于CON组(P<0.01),而TGP组较DRB组降低(P<0.01)。TGP组肾小球病变较DRB组轻。结论 TGP对大鼠DRB肾病有辅助治疗作用,其机制可能与其下调JAK2/STAT3通路有关。

Objective To explore the effect and underlying mechanism of total glucosides of Paeony（TGP）in rats with daunorubicin（DRB）-induced nephropathy.Methods The nephropathy model of 16 male SD rats was established successfully by intravenous injection of DRB 1mg/100 g,which were equally assigned into two groups of A（treated with gavage of TGP 10mg/100 g daily for8weeks）and B（treated with normal saline as model control）.Another 8rats were taken as blank control（group C）.Serum levels of total protein（TP）,total cholesterol（TC）,serum creatinine（SCr）,blood urea nitrogen（BUN）and 24-h urine protein were detected after treated for 8 weeks.Renal pathological changes were observed by HE staining and the expressions of JAK2 and STAT3mRNA and p-JAK2 and p-STAT3 protein were detected by RT-PCR and Western blot.Results Compared with group C,TP was lower,but TC,SCr,BUN and 24-h urine protein were higher,in groups of A and B（P〈0.01）.Compared with group B,TP was lower,but TC,SCr,BUN and 24-h urine protein were higher,in group A（P〈0.01）.Compared with group C,the expressions of JAK2 and STAT3mRNA and p-JAK2 and p-STAT3 protein were higher in groups of A and B（P〈0.01）,which were lower in group A than those in group B（P〈0.01）.The glomerular lesion was slighter in group A than that in group B.Conclusion TGP is effective as an adjuvant therapy in treating DRB-induced nephropathy in rats,for which the mechanism might be related to the downregulation of JAK2/STAT3 pathway.