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芪附汤调节ERK1/2信号通路改善UUO阳虚证模型肾间质纤维化的作用和机制

Keywords: 肾小管/间质纤维化,芪附汤,肾小管上皮细胞间充质转分化,ERK1/2信号通路

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Abstract:

目的:探讨芪附汤改善阳虚证模型鼠肾间质纤维化(RIF)的作用和机制。方法:将大鼠随机分为假手术组(A组)、模型组(B组)、芪附汤组(C组)、依那普利组(D组)。通过腺嘌呤灌胃联合单侧输尿管接扎术(UUO)的方法而建立RIF模型。造模成功后,C,D组大鼠分别经灌胃给予芪附汤水煎液或依那普利悬浊液;其余2组大鼠经灌胃给予蒸馏水,共干预3周。各在药物和蒸馏水干预前和干预后第1,2,3周末,分别称量大鼠体重,并检测24h尿蛋白排泄量(Upro)、尿β2-微球蛋白(Uβ2-MG)、尿N-乙酰-β-D-氨基葡萄糖苷(NAG)酶。药物干预第3周末,处死全部大鼠,抽取血液,摘除左肾,称重,并留取相应标本,观察肾脏外观和肾小管/间质形态;检测血清环磷酸腺苷(cAMP)、环磷酸鸟苷(cGMP)、肌酐(Scr)、尿素氮(BUN)和尿酸(UA);检测肾组织中上皮型黏钙蛋白(E-cadherin)、α-平滑肌肌动蛋白(α-SMA)、转化生长因子-β1(TGF-β1)、结缔组织生长因子(CTGF)、细胞外调节激酶(ERK1/2)和磷酸化ERK1/2(p-ERK1/2)蛋白相对表达量。结果:芪附汤可以改善模型鼠血清中降低的cAMP和cAMP/cGMP;减少模型鼠升高的Uβ2-MG、尿NAG酶,改善肾间质细胞外基质及其胶原沉积,上调肾组织E-cadherin蛋白表达,下调肾组织α-SMA,TGF-β1,CTGF,p-ERK1/2蛋白表达;但是,对Scr,BUN,UA没有影响。芪附汤改善RIF的作用优于依那普利。结论:芪附汤可以改善模型鼠阳虚证指标以及尿β2-MG、尿NAG酶排泄,它可能是通过上调肾组织E-cadherin蛋白表达,下调肾组织α-SMA,TGF-β1,CTGF以及ERK1/2信号通路中关键信号分子——p-ERK1/2蛋白表达,改善肾小管EMT,从而减轻RIF。

References

[1]  Zhang L,Wang F,Wang L,et al. Prevalence of chronic kidney disease in China:a cross-sectional survey [J]. Lancet,2012,379(9818):815.
[2]  Rodriguez-Iturbe B, Johnson R J,Herrera-Acosta J. Tubulointerstitial damage and progression of renal failure [J]. Kidney Int Suppl,2005,(99):S82.
[3]  Kalluri R N,Eilson E G. Epithelial-mesenchymal transition and its implications for fibrosis [J]. J Clin Invest,2003,112(12):1776.
[4]  Farris A B,Colvin R B. Renal interstitial fibrosis: mechanisms and evaluation [J]. Curr Opin Nephrol Hypertens,2012,21(3):289.
[5]  Tang W W,Van G Y,Qi M. Myofibroblast and alpha 1(Ⅲ)collagen expression in experimental tubulointerstitial nephritis [J]. Kidney Int,1997,51(4):926.
[6]  Ohashi R,Shimizu A,Masuda Y,et al. Peritubular capillary regression during the progression of experimental obstructive nephropathy [J]. Am Soc Nephrol,2002,13(7):1795.
[7]  Mori T,Kawara S,Shinozaki M,et al.Role and interaction of connective tissue growth factor and transforming growth factor-β in persistent fibrosis: a mouse fibrosis model [J].J Cell Physiol,1999,181(1):153.
[8]  Suvi-K L,Lari H,David Liu,et al. Smad3 and extracellular signal-regulated kinase 1/2 coordinately mediate transforming growth factor-induced expression of connective tissue growth factor in Human fibroblasts [J]. J Invest Dermatol,2005,124(6):1162.
[9]  Liu X,Ostrom R S,Insel P A. cAMP-elevating agents and adenylyl cyclase overexpression promote an antifibrotic phenotype in pulmonary fibroblasts [J]. Am J Physiol Cell Physiol, 2004,286(5):C1089.
[10]  Duncan M R,Frazier K S,Abramson S,et al. Connective tissue growth factor mediates transforming growth factorB-induced collagen synthesis:down-regulation by cAMP [J]. FASEB J,1999,13(13):1774.
[11]  祝胜郎,常巨平. ERK1/2信号蛋白在单侧尿路梗阻大鼠肾组织中的表达[J].中国医药导报,2007,4(18):21.
[12]  Mulsow J J,Watson R W,Fitzpatrick J M,et al. Transforming growth factor-beta promotes profibrotic behavior by serosal fibroblasts via PKC and ERK1/2 mitogen activated protein kinase cell signaling [J]. Ann Surg,2005,42(6):880.
[13]  Docherty N G,O\'Sullivan O E, Healy D A,et al. Evidence that inhibition of tubular cell apoptosis protects against renal damage and development of fibrosis following ureteric obstruction [J]. Am J Physiol Renal Physiol,2006,290(2):4.
[14]  刘晓倩,赵宗江,闫军堂,等.益气活血降浊复方对单侧输尿管梗阻大鼠肾小管上皮细胞转分化影响的实验研究[J].中华中医药学刊,2012,30(2):253.
[15]  Xie X S,Yang M,Liu H C,et al.Influence of ginsenoside Rg1,a panaxatriol saponin from Panax notoginseng,on renal fibrosis in rats with unilateral ureteral obstruction[J]. J Zhejiang Univ Sci B,2008,9(11):885.
[16]  邵命海,肖静,王毅兴,等.从"肾主生殖"角度评价腺嘌呤与氢化可的松诱导的肾阳虚模型[J].上海中医药杂志,2008,42(2):57.
[17]  孙景波,华荣,曾星,等.用以药测证原理研究慢性肾衰大鼠模型的中医证候属性[J].现代中医药,2004,3(2):61.
[18]  Suzuki K,Wang R,Kubota H,et al. Kinetics of biglycan, decorin and thrombospond in linmercuric chlorides-induced renal tubulointerstitial fibrosis [J]. Exp Mol Patho1,2007,9(1):68.
[19]  刘玉宁. 肾间质纤维化的中医病机和治法探讨[J]. 新中医,2006,11(38):1.
[20]  肖静,王毅兴,高建东,等.肾阳虚证的研究进展[J].上海中医药大学学报,2008,22(2):73.

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