Department of Nephrology, Wenzhou TCM Hospital Affiliated to Zhejiang, University of Traditional Chinese Medicine, Wenzhou 325000, China.
J Tradit Chin Med. 2012 Jun;32(2):229-33. doi: 10.1016/s0254-6272(13)60016-3.
To determine the mechanisms by which kangxianling (KXL) treats renal interstitial fibrosis using a customized gene chip.
Twelve out of 18 specific pathogen-free sprague dawley (SPF SD) rats underwent a unilateral ureteral occlusion. These rats were then randomly assigned into either the model unilateral ureteral obstruction (UUO) or kangxianling (KXL) group. The other six rats were assigned to the sham-operated group. The UUO and sham-operated groups were given normal saline via intragastric administration, whereas the KXL group was given KXL via intragastric administration. All rats were sacrificed for renal tissue collection (i.e., left nephridial tissue), and the detection of genetic changes with the customized chip.
Compared to the sham-operated group, transforming growth factor-beta (TGF-beta), Smad2, and Smad3 genes were significantly up-regulated in the UUO group, with >1.5-fold rise (P < 0.01). The Smad7 gene was significantly reduced in the UUO versus sham-operated group, with a down-regulation of >1.5-fold (P < 0.01). In the KXL group, TGF-beta1, Smad2, and Smad3 genes were significantly reduced compared to the UUO group, with a down-regulation of >1.5-fold (P < 0.01), whereas the Smad7 gene was significantly increased compared to the UUO group, with an up-regulation of > 1.5-fold (P < 0.01).
It was found that KXL can significantly reduce the gene levels of TGF-beta1, Smad2, and Smad3. Immunohistochemistry findings also revealed significantly lower TGF-beta1/Smads-mediated gene transcription activity. These findings suggest that KXL may negatively regulate the TGF-beta1/Smads signal pathway to inhibit the occurrence of renal fibrosis.
利用定制基因芯片确定抗纤灵治疗肾间质纤维化的作用机制。
18 只无特定病原体 SPF 大鼠中 12 只进行单侧输尿管结扎。将这 12 只大鼠随机分为模型单侧输尿管梗阻（UUO）组和抗纤灵（KXL）组。另 6 只大鼠作为假手术组。UUO 组和假手术组给予生理盐水灌胃，KXL 组给予抗纤灵灌胃。处死所有大鼠取肾组织（即左肾组织），并用定制芯片检测基因变化。
与假手术组相比，UUO 组转化生长因子-β（TGF-β）、Smad2 和 Smad3 基因明显上调，上调超过 1.5 倍（P<0.01）。Smad7 基因在 UUO 组与假手术组相比明显下调，下调超过 1.5 倍（P<0.01）。KXL 组 TGF-β1、Smad2 和 Smad3 基因与 UUO 组相比明显下调，下调超过 1.5 倍（P<0.01），Smad7 基因与 UUO 组相比明显上调，上调超过 1.5 倍（P<0.01）。
发现抗纤灵可显著降低 TGF-β1、Smad2 和 Smad3 基因水平。免疫组化结果还显示 TGF-β1/Smads 介导的基因转录活性明显降低。这些发现表明，抗纤灵可能通过负调控 TGF-β1/Smads 信号通路抑制肾纤维化的发生。
