Zhao Jian-rong, Qu Lei, Li Xiao-mei
Department of Nephrology, Peking University First Hospital; Peking University Institute of Nephrology, Beijing 100034, China.
Beijing Da Xue Xue Bao Yi Xue Ban. 2004 Apr;36(2):119-23.
To investigate the preventive and therapeutic effects of Astragalus and Angelica mixture A&A on renal tubulointerstitial fibrosis after unilateral ureteral obstruction UUO in rats and their mechanisms.
UUO rats were randomly divided into Sham, UUO, A&A or ACEI groups. A&A, ACEI or the same amount of water was administered by gavage beginning 24 hours before UUO preparation and continued through ten days after UUO. Sera and the kidney tissues were collected from each group on the tenth day. Scr and BUN were measured. Trichrome staining, measurement of tubulo interstitial damage index and immunohistochemical studies localizing alpha-smooth muscle actin alpha-SMA , TGF-beta1, fibronectin FN , laminin LN were carried out.
In UUO rats, the tubular-interstitial damage index, the expressions of alpha-SMA, TGF-beta1, FN and LN were all increased compared with those of Sham group. The tubulo interstitial damage index had positive correlation with expressions of alpha-SMA, TGF-beta1, FN and LN. A&A significantly ameliorated deterioration of renal function, tubulo interstitial damage index and inhibited the over-expressions of alpha-SMA, TGF-beta1, FN and LN in UUO rats. These anti-fibrotic effects were similar to those affected by ACEI.
In renal interstitial fibrosis-induced UUO rats, A&A retard the progression of renal fibrosis and renal function deterioration by inhibiting myofibroblasts and suppressing TGF-beta1 expression, which may consequently result in a decreased production of extracellular matrix.
探讨黄芪当归合剂(A&A)对大鼠单侧输尿管梗阻(UUO)后肾小管间质纤维化的防治作用及其机制。
将UUO大鼠随机分为假手术组、UUO组、A&A组或ACEI组。在UUO造模前24小时开始通过灌胃给予A&A、ACEI或等量的水,并持续至UUO后10天。在第10天从每组收集血清和肾组织。检测血肌酐(Scr)和血尿素氮(BUN)。进行三色染色、测量肾小管间质损伤指数以及对α平滑肌肌动蛋白(α-SMA)、转化生长因子-β1(TGF-β1)、纤连蛋白(FN)、层粘连蛋白(LN)进行免疫组化定位研究。
与假手术组相比,UUO大鼠的肾小管间质损伤指数、α-SMA、TGF-β1、FN和LN的表达均增加。肾小管间质损伤指数与α-SMA、TGF-β1、FN和LN的表达呈正相关。A&A显著改善了UUO大鼠肾功能的恶化、肾小管间质损伤指数,并抑制了α-SMA、TGF-β1、FN和LN的过度表达。这些抗纤维化作用与ACEI的作用相似。
在UUO诱导的肾间质纤维化大鼠中,A&A通过抑制肌成纤维细胞和抑制TGF-β1表达来延缓肾纤维化的进展和肾功能恶化,这可能进而导致细胞外基质产生减少。