Gao Hong-Yu, He Xiao-Feng, Shao Ju-Fang
Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan.
Zhongguo Zhong Xi Yi Jie He Za Zhi. 2007 Jun;27(6):535-9.
To study the effect of Kurarinone on renal tubular epithelial cell-mesenchyma (ECM) trans-differentiation in rats with renal interstitial fibrosis and to explore its possible mechanisms.
The 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 beta1 (TGF-beta1), Smad3, alpha-smooth muscle actin (alpha-SMA) and collagen I (Col I) in kidney were determined with immunohistochemistry. And the expressions of TGF-beta1 and alpha-SMA mRNA in renal tissue were determined using reverse transcription polymerase chain reaction (RT-PCR).
The expression of TGF-beta1, Smad3, alpha-SMA and Col I 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-beta1 and alpha-SMA mRNA expressions in KTG were significantly lower than those in the UUO group determined at the corresponding time points (P < 0.05).
Kurarinone could down-regulate the expression of TGF-beta1 and Col I, 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.
研究苦参碱对肾间质纤维化大鼠肾小管上皮细胞-间充质转分化（ECM）的影响，并探讨其可能机制。
采用单侧输尿管梗阻（UUO）法建立大鼠肾间质纤维化模型。将雄性Sprague-Dawley大鼠随机分为3组，即假手术组、UUO组和苦参碱治疗组（KTG）。造模后，KTG组大鼠每天腹腔注射苦参碱100mg/kg。UUO术后第7、14和21天分别处死每组5只大鼠。检测大鼠血清尿素氮（BUN）、血清肌酐（SCr）、总蛋白（TP）和白蛋白（ALB）水平以及24小时尿蛋白排泄量。采用PAS和Masson染色观察肾组织病理变化。用免疫组织化学法检测肾组织中转化生长因子β1（TGF-β1）、Smad3、α-平滑肌肌动蛋白（α-SMA）和Ⅰ型胶原（ColⅠ）的表达。并用逆转录聚合酶链反应（RT-PCR）检测肾组织中TGF-β1和α-SMA mRNA的表达。
与UUO组相比，KTG组中TGF-β1、Smad3、α-SMA和ColⅠ的表达分别显著降低，且KTG组肾小管损伤和肾间质纤维化程度改善更明显。在相应时间点，KTG组中TGF-β1和α-SMA mRNA表达显著低于UUO组（P<0.05）。
苦参碱可下调TGF-β1和ColⅠ的表达，抑制EC-M转分化，抑制肌成纤维细胞的活化和增殖。其可能途径可能是通过下调Smad3表达来干扰其对细胞间信号转导的诱导，从而改善肾间质纤维化。
