| 高红宇,何晓峰,邵菊芳,易艳,黄晓丽,刘晓城.苦参素对肾间质纤维化大鼠肾小管上皮细胞-间质转分化的影响[J].,2007,(6):535-539 |
| 苦参素对肾间质纤维化大鼠肾小管上皮细胞-间质转分化的影响 |
| Effect of Kurarinone on Renal Tubular Epithelial Cell-Mesenchyma Trans-differentiation in Rats with Renal Interstitial Fibrosis |
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| DOI： |
| 中文关键词: 苦参素 肾间质纤维化 肾小管上皮细胞-间质转分化 |
| 英文关键词:Kurarinone renal interstitial fibrosis renal tubular epithelial cell-mesenchyma trans-differentiation |
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| 中文摘要: |
| 目的探讨苦参素对肾间质纤维化大鼠肾小管上皮细胞-间质转分化的影响及可能机制。方法大鼠行单侧输尿管结扎(UUO)建立肾小管间质纤维化模型。实验分为假手术、UUO及苦参素治疗组。治疗组在UUO的基础上每天以苦参素100mg/kg腹腔注射。各组于术后第7、14、21天分别处死5只大鼠,分别检测大鼠血清总蛋白(TP)、白蛋白(ALB)、尿素氮(BUN)、肌酐(SCr)及24h尿蛋白定量。用PAS及Masson染色法观察肾脏病理改变。用免疫组织化学法观察转化生长因子β1(TGF-β1)、Smad3、α-平滑肌肌动蛋白(α-SMA)及Ⅰ型胶原(ColⅠ)的表达。用RT-PCR法测定肾组织TGF-β1及α-SMA mRNA水平。结果与UUO组比较,苦参素治疗组肾脏TGF-β1、Smad3、α-SMA及ColⅠ的表达明显减少,肾小管损害和肾间质纤维化的程度也明显减轻。治疗组TGF-β1 mRNA及α-SMA mRNA表达显著低于对应时间点的UUO组。结论苦参素可下调TGF-β1、ColⅠ的表达,抑制肾小管上皮细胞转分化及肌成纤维细胞的活化与增殖,其作用途径可能是通过下调Smad3的表达,从而干预Smad3介导的细胞内信号转导,最终减轻肾间质纤维化。 |
| 英文摘要: |
| Objective To study the effect of Kurarinone on renal tubular epithelial cell-mesenchyma (EC-M) trans-differentiation in rats with renal interstitial fibrosis and to explore its possible mechanisms. MethodsThe rat model of renal interstitial fibrosis was established by unilateral ureteral obstruction (UUO). Sprague-Dawley male rats were randomly divided into 3 groups, the sham-operated group, the UUO group and the Kurarinone treated group (KTG). Rats in the KTG were intraperitoneally injected with Kurarinone 100 mg/kg daily after modeling. Five rats of each group were killed respectively at day 7, 14 and 21 after UUO. The serum levels of blood urea nitrogen (BUN), serum creatinine (SCr), total protein (TP) and albumin (ALB), 24-h urinary protein excretion in rats were measured. Pathological changes of renal tissue were observed by PAS and Masson stain. The expression of transforming growth factor β1 (TGF-β1), Smad3, α-smooth muscle actin (α-SMA) and collagen Ⅰ (ColⅠ) in kidney were determined with immunohistochemistry. And the expressions of TGF-β1 and α-SMA mRNA in renal tissue were determined using reverse transcription polymerase chain reaction (RT-PCR). Results The expression of TGF-β1, Smad3, α-SMA and ColⅠ in the KTG was significantly decreased as compared with that in the UUO group respectively, and the degree of tubular damage and renal interstitial fibrosis was also ameliorated more obviously in the KTG. The TGF-β1 and α-SMA mRNA expressions in KTG were significantly lower than those in the UUO group determined at the corresponding time points (P<0.05). Conclusion Kurarinone could down-regulate the expression of TGF-β1 and ColⅠ, inhibit EC-M trans-differentiation, suppress the activation and proliferation of myofibroblast. The probable pathway may be by way of down-regulating Smad3 expression to interfere its induction on intercellular signal transduction and consequently ameliorate renal interstitial fibrosis. |
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