泽兰对UUO大鼠肾脏核转录因子及血管内皮生长因子的影响

Effect of Lycopus on Expression of NF-κB and VEGF in Rats with Unilateral Ureteral Obstruct

目的观察泽兰对单侧输尿管结扎(UUO)大鼠肾小管间质纤维化及肾功能的影响。方法采用UUO大鼠模型,将32只雄性SD大鼠随机分为4组,即假手术组、模型组、泽兰组和替米沙坦组,术后每日1次灌胃,假手术组和模型组给予5mL生理盐水,泽兰组按6g/(kg·d)给药,替米沙坦组按10mg/(kg·d)给药,14d后处死大鼠,收集血清测定血肌酐(Scr)和尿素氮(BUN),进行HE染色观察肾组织病理改变,Masson染色进行肾间质纤维化评估,应用免疫组织化学方法检测梗阻侧肾组织核转录因子(NF-κB)和血管内皮生长因子(VEGF)的表达。结果模型组与两治疗组大鼠血清Scr、BUN上升,与假手术组比较有显著性差异(P<0.05);模型组、泽兰组、替米沙坦组肾间质纤维化程度均较假手术组明显增高(P<0.05);模型组NF-κB表达增加,VEGF表达减少,与假手术组相比差异有显著意义(P<0.01);泽兰组与模型组相比,NF-κB表达下降,VEGF表达上升,差异显著(P<0.05);泽兰组与替米沙坦组各指标比较均无显著性差异(P>0.05)。结论泽兰能通过下调NF-κB和增加VEGF表达而抑制单侧输尿管梗阻大鼠肾间质纤维化,其改善肾纤维化作用与替米沙坦无明显差异。

Objective To study the effect of Lycopus on the expression of NF-κB and VEGF during the progression of renal interstitial fibrosis in rat unilateral ureteral obstruction（UUO） model,and to explore the mechanisms.Methods：The obstructive nephropathy model was established by unilateral ureteral obstruction（UUO）,32 rats were equally randomized into sham group,model group （UUO group）,Lycopus treatment group （UUO ＋ Lycopus） and Telmisartan treatment group （UUO ＋ Telmisartan）.Gastric perfusion was performed daily after modeling：5ml normal saline was given to sham group and model group;6g/（kg·d） Lycopus to Lycopus treatment group;10mg/（kg·d） Telmisartan to Telmisartan treatment group.At 14th day,serum creatinine （Scr） and blood urea nitrogen （BUN） were measured as the rats were sacrificed for sampling.Renal interstitial fibrosis （RIF） was evaluated with Masson staining.The expressions of NF-κB and VEGF in renal tissue was examined by immunohistochemistry.Results Compared with sham group,both treatment groups and UUO group on Scr BUN had significant difference （P 0.05）.In comparison with the sham group,the renal interstitial fibrosis was obviously greater in the rest groups.The expression of NF-κB significantly increased（P 0.05） and the expression of VEGF significantly decreased （P 0.05） in UUO group,as compared with sham group （P 0.01）.In comparison with the UUO group,the expression of NF-κB reduced （P 0.05） and the expression of VEGF increased （P 0.05） in Lycopus treatment group.But two treatment groups were observed no significant difference （P 0.05）.Conclusion Lycopus lucidus Turcz.var.hirtus Reg.may protect the kidney by down-regulating the expression of NF-κB and up-regulating the expression of VEGF to inhibit the progression of renal interstitial fibrosis,its effect on attenuating the renal interstitial fibrosis has no significant difference comparing with Telmisartan.