摘要
目的探讨盐酸小檗碱对慢性肾功能衰竭(Chronic renal failure,CRF)大鼠肾间质纤维化的改善作用及其机制研究。方法40只SPF级SD雄性大鼠随机分为对照组,模型组,盐酸小檗碱低、高剂量组。利用连续灌胃21 d250 mg/kg腺嘌呤溶液的方法建立大鼠CRF模型,对照组给予等量的生理盐水。低、高剂量组分别灌胃给予150、300 mg/kg盐酸小檗碱,连续治疗28 d。观察大鼠血清中肌酐(Scr)、尿素氮(BUN)及24 h尿蛋白(24 h UTP)水平;HE染色检测肾组织病理变化;试剂盒检测超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性及丙二醛(MDA)含量;Western blot检测大鼠肾组织中转化生长因子-β1(TGF-β1)、胶原蛋白Ⅰ(CollagenⅠ)、α-平滑肌肌动蛋白(α-SMA)、第10号染色体缺失的磷酸酯酶-张力蛋白同源物(PTEN)、磷脂酰肌醇激酶-3(PⅠ3K)、磷酸化磷脂酰肌醇激酶-3(p-PⅠ3K)、蛋白激酶B(AKT)及磷酸化蛋白激酶B(p-AKT)的表达。结果与模型组相比,盐酸小檗碱组血清Scr、BUN及尿液中24 h UTP含量明显降低(P<0.05,P<0.01),并能显著改善大鼠肾组织损伤;盐酸小檗碱还能够增加SOD、GSH-Px活性,降低MDA含量(P<0.05);盐酸小檗碱能够减少TGF-β1、CollagenⅠ及α-SMA的表达(P<0.05),还能够增加PTEN蛋白的表达并抑制PⅠ3K、AKT蛋白的磷酸化(P<0.05)。结论盐酸小檗碱对慢性肾功能衰竭大鼠具有肾保护作用,能延缓肾间质纤维化,其作用机制可能与调控PTEN/PⅠ3K/AKT信号通路相关蛋白表达有关。
Objective To investigate the effect and mechanism of berberine hydrochloride on renal interstitial fibrosis in rats with chronic renal failure(CRF).Methods Forty SPF SD male rats were randomly divided into control group,model group,and berberine hydrochloride low and high dose groups.Rat CRF model was established by continuous gavage of 250 mg/kg adenine solution for 21 days.Lowand high-dose groups were given 150 mg/kg and 300 mg/kg berberine hydrochloride by intragastric(i.g.)administration for 28 days.The levels of creatinine(Scr),urea nitrogen(BUN)and 24 h urine protein(24 h UTP)were observed;HE staining was used to detect the pathological changes of renal tissues;The superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)activity and malondialdehyde(MDA)content were detected;Western blot was used to detect the expression of TGF-β1,CollagenⅠ,α-SMA,PTEN,PI3K,p-PI3K,AKT and p-AKT.Results Compared with the model group,the content of Scr,BUN and 24 h UTP in berberine hydrochloride group was significantly lower(P<0.05,P<0.01),and significantly improved rat kidney tissue injury;Berberine hydrochloride also increased SOD and GSH-Px activity,and decreased the content of MDA(P<0.05).Berberine hydrochloride decreased the expression of TGF-β1,collagenⅠandα-SMA(P<0.05);Berberine hydrochloride also increased the expression of PTEN protein,while inhibiting the phosphorylation of PI3K and AKT proteins.Conclusion Berberine hydrochloride exerts renal protective effect and delays renal interstitial fibrosis in rats with chronic renal failure,which the mechanism may be related to the regulation of PTEN/PI3K/AKT signaling pathway-related protein expression.
作者
于艳
赵万超
许烨
远方
YU Yan;ZHAO Wanchao;XU Ye;YUAN Fang(Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110032,Liaoning,China)
出处
《辽宁中医药大学学报》
CAS
2020年第3期26-30,共5页
Journal of Liaoning University of Traditional Chinese Medicine
基金
辽宁省自然科学基金指导计划(20170540607)。
