补肾健脾活血解毒煎剂对单侧输尿管梗阻大鼠TGF-β1及α-SMA表达的影响

Effects of Bushen Huoxue Jiedu Jianji(补肾健脾活血解毒煎剂, BSHXJDJJ) on TGF-βl and α-SMA in Rats with Unilateral Ureteral Obstruction

目的:研究补肾健脾活血解毒煎剂对单侧输尿管梗阻大鼠肾间质α-平滑肌肌动蛋白(α-SMA)、转化生长因子-β1(TGF-β1)表达的影响,探讨其抗肾间质纤维化的作用机制。方法:建立大鼠单侧输尿管梗阻(UUO)模型,50只SD大鼠随机分为假手术组、模型组、代文组、补肾健脾活血解毒煎剂低、中剂量组,于造模4周后腹主动脉采血检测血清肌酐(Scr)、尿素氮(BUN),收集24 h尿液检测N-乙酰-β-D-氨基葡萄糖苷酶(N-acetyl-β-D-glucosaminidase,NAG)、β2-微球蛋白(β2-microglobulin,β2-MG),取梗阻侧肾组织,HE、Mason染色观察肾小管间质病变,免疫组织化学染色观察α-SMA、TGF-β1在肾间质的阳性染色表达,并进行半定量分析。结果:与假手术组比较,模型组大鼠Scr、BUN、尿NAG、β2-MG水平以及α-SMA、TGF-β1阳性表达显著升高(P<0.01);与模型组比较,补肾健脾活血解毒煎剂低、中剂量组大鼠Scr、BUN水平降低,尿NAG、β2-MG排泄减少(P<0.05或P<0.01),与代文组相当;补肾健脾活血解毒煎剂低、中剂量组和代文组α-SMA、TGF-β1阳性表达均显著下调(P<0.01)。结论:补肾健脾活血解毒煎剂可能通过改善肾小球、肾小管功能,抑制α-SMA、TGF-β1的表达,从而抑制肾小管上皮细胞间充质转分化,达到改善肾间质纤维化的作用。

Objective： To investigate the effects of BSHXJDJJ on the renal interstitium alpha-smoothmuscle actin（α-SMA） and transforming growthfactor-betal （TGF-β1） expression in unilateral ureteral obstruction （UUO）rats, and to illuminate the possible mechanisms against renal interstitial fibrosis. Methods： The rat modle with unilateral ureteral obstruction （UUO） was created. The 50 Sprague-Dawley rats were randomly divided into Sham-op- erated, modle, Diovan, and the low and middle dose BSHXJDJJ groups. On the 4th week after treatment, the serum creatinine（Scr）, blood urea nitrogen（BUN）, the N-acetyl-β-D-glucosaminidase（NAG）, andβ2-microglobuliu （β2-MG）in 24 h urine were detected; the obstructed kidney was taken outand measured by HE, Masson, and immunohistochemistry staining for semiquantitative analysis of a-SMA and TGF-β1. Results： The level of Scr, BUN, NAG,β2-MG,α-SMA and TGF-β1 in model group increased （P〈0.01）, compared with those in the sham-ope rated group. In comparison with the model group, the lever of Ser, BUN, NAG and β2-MG were significantly lower in the low and middle dose BSHXJDJJ groups （P〈0.05 or P〈0.01）;and the expression of positive staining for α-SMA and TGF-β1 were significantly down-regulated in the low and middle dose BSHXJDJJ groups and Diovan group （P〈0.01）. Conclusion： The BSHXJDJJ can degrade renal interstitial fibrosis by improving renal function, inhibiting the expression of a-SMA and TGF-β1, and inhibiting renaltubule epithelial-mesenchymal transition.