关木通与抗生素致急性肾小管坏死细胞生物学特征的比较研究

目的：通过比较关木通致急性肾小管坏死(Manchurian Dutchmanspipe—acute tubular necrosis，MD—ATN)与抗生素致ATN(antmiotic—acute tubular necrosis，A—ATN)两组病变中肾小管间质细胞表型特征及细胞外基质分泌的异同，初步探讨两者预后明显差异的细胞生物学机制。方法：应用免疫组化SP法观察4例MD—ATN和5例A—ATN患者的。肾活检组织标本中，增殖细胞核抗原(PCNA)、表皮细胞生长因子(EGF)、α-平滑肌肌动蛋白(α—SMA)、纤维连接蛋白(FN)、Ⅲ型胶原、Ⅳ型胶原、转化生长因子β1(TGFβ1)和结缔组织生长因子(CTGF)表达程度的异同。针对两组患者临床预后的显著差别，重点从损伤修复及纤维化发生两个方面对上述指标进行分析。结果：(1)MD—ATN组肾小管上皮细胞(RTEC)PCNA阳性率以及EGF表达均显著低于A—ATN组(P<0．01)；(2)两组肾小管间质内α—SMA表达均增加，差异无显著性；(3)两组肾间质内均出现TGFβ1阳性细胞浸润以及CTGF的显著表达，两组间比较差异无显著性；(4)MD-ATN组肾间质内FN、Ⅲ型和Ⅳ型胶原的表达均较A—ATN组明显增加(P<0．01)。结论：(1)与A—ATN组比较。MD—ATN患者RTEC损伤后自身修复能力减低，EGF低表达可能为其修复不良的原因之一。(2)MD-ATN与A—ATN患者肾间质内α—SMA、TGFβ1和CTGF均呈高表达，但仅MD—ATN患者的肾间质内出现细胞外基质沉积，提示其病变慢性化的趋向可能与细胞外基质降解因子和(或)内源性抗纤维化因子减低有关。

A Comparative Study of Manchurian Dutchmanspipe and Antibiotics Induced Acute Tubular Necrosis in Renal Cellular Biological Features

OBJECTIVE: To explore the possible cell biological mechanisms of the difference in prognosis between the acute tubular necrosis (ATN) induced by Manchurian Dutchmanspipe (MD-ATN) and that by antibiotics (A-ATN), by means of comparing their renal tubular mesenchymal cell phenotype characteristics and extra-cellular stroma secretion. METHODS: The expression of proliferative cell nuclear antigen (PCNA), epithelial cell growth factor (EGF), alpha-smooth muscle actin (alpha-SMA), fibronectin (FN), collagen type III and IV, transforming growth factor beta 1 (TGF beta 1) and connective tissue growth factor in renal biopsy samples of patients with MD-ATN (4 patients) and A-ATN(5 patients) were compared with immunohistochemical SP method. The analysis of above-mentioned parameters on repairing of injury and development of fibrosis was stressed for the obvious difference in clinical prognosis between the two groups. RESULTS: (1) The PCNA positive rate of renal tubular epithelial cell (RTEC) and EGF expression in the MD-ATN group were significantly lower than those in the A-ATN group respectively (P < 0.01); (2) Renal tubular mesenchymal alpha-SMA level increased in both groups with no significant difference; (3) TGF beta 1 positive cell infiltration and obvious CTGF expression revealed in renal mesenchyma of both groups with insignificant difference; (4) FN, collagen III and IV levels were significantly higher in the MD-ATN group than that in the A-ATN group (P < 0.05). CONCLUSION: (1) As compared with A-ATN group, the RTEC auto-repairing ability was lower in the DM-ATN group, lower expression of EGF might be one of the mechanisms of its poor repair; (2) High expression of alpha-SMA, TGF beta 1 and CTGF presented in all patients with ATN, but extra-cellular stromal deposit appeared only in the renal stroma of patients with MD-ATN, suggesting that its chronical trend might be related with the reducing of extra-cellular stromal degradation factor and/or endogenous anti-fibrosis factor.