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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 investigate the therapeutic effect and intervention mechanism of total glucosides of paeony (TGP) on daunorubicin (DRB) nephropathy in rats. Methods Twenty-six male Sprague-Dawley rats were divided into two groups by tail vein injection of DRB 1 mg / 100g to establish nephropathy model: TGP group was given TGP intragastrically for 10 mg / 100g daily for 8 weeks; DRB group served as model control. Another 8 normal rats as a blank control (CON) group. DRB group and CON group were given the same amount of saline gavage. Serum total protein (TP), total cholesterol (TC), serum creatinine (SCr), blood urea nitrogen (BUN) and 24-h urinary protein were measured 8 weeks after gavage. Pathological changes of kidney were observed by HE staining. The relative expression of JAK2 and STAT3 mRNA was detected. The relative expression of phosphorylated JAK2 (p-JAK2) and p-STAT3 protein was detected by Western blot. Results The TP of DRB group and TGP group were lower than that of CON group, while the contents of TC, SCr, BUN and 24-h urinary protein in CON group were higher than those in CON group (P <0.01) BUN and 24-h urinary protein were lower than the DRB group (P <0.01). The relative expression of JAK2, STAT3mRNA and p-JAK2, p-STAT3 protein in DRB group and TGP group were higher than those in CON group (P <0.01), while those in TGP group were lower than those in DRB group (P <0.01). Glomerular lesions in TGP group were lighter than those in DRB group. Conclusions TGP can adjuvant therapy on rat DRB nephropathy, which may be related to its downregulation of JAK2 / STAT3 pathway.