大黄酸抑制转化生长因子β1诱导的肾小管上皮细胞肥大及细胞外基质积聚

目的：观察大黄酸对TGFβ1诱导的肾近端小管上皮细胞肥大及细胞外基质的影响。方法：在体外以TGFβ1（2μg/L）刺激LLC－PK1细胞，诱导细胞肥大和细胞外基质合成的增加。同时，以不同浓度的大黄酸处理细胞，检测细胞体积、蛋白质含量以及^3H]亮氨酸掺入以观察细胞肥大的变化。此外，检测细胞培养上清液中的纤维素增生（FN）含量。^3H]脯氨酸掺入以及细胞胶原IV及FN mRNA的表达以观察大黄酸对细胞外基质的影响。结果：TGFβ1（2μg/L）刺激可以导致LLC－PK1细胞出现细胞肥大，表现为细胞体积、细胞内蛋白量及^3H]亮氨酸掺入量明显增加，大黄酸治疗后细胞体积及细胞内蛋白量降低。TGFβ1也能明显增加LLC－PK1细胞^3H]脯氨酸掺入量，培养上清液中FN含量，以及细胞内胶原IV和FN mRNA的表达。大黄酸则能抑制上述细胞外基质合成的影响，明显降低细胞内胶原IV和FN mRNA表达水平。结论：大黄酸可以逆转TGFβ1诱导的近端肾小管上皮细胞肥大，抑制TGFβ1刺激的细胞外基质合成，这可能是大黄酸预防或改善糖尿病肾脏病变、延缓糖尿病肾病进展的作用机制之一。

Rhein inhibits renal tubular epithelial cell hypertrophy and extracellular matrix accumulation induced by transforming growth factor

AIM: To investigate the effects of rhein on cell hypertrophy and accumulation of extracellular matrix (ECM) in the renal tubular epithelial cells. METHODS: LLC-PK1 cells were incubated with transforming growth factor beta1 (TGFbeta1) 2 microg/L for 24 h to induce cell hypertrophy and production of ECM. To evaluate the effects of rhein on inhibiting the action of TGFbeta1, cell volume, cellular protein level, and 3H]leucine incorporation in LLC-PK1 cells treated with rhein at different concentrations were measured. In addition, the 3H]proline incorporation, level of fibronectin (FN) in supernatant, and mRNA expression of collagen IV and FN were also detected in rhein treated cells. RESULTS: The cell volume, cellular protein content, and 3H]leucine incorporation were markedly increased in LLC-PK1 cells after TGFbeta1 stimulation as compared with control (P < 0.01), and this TGFbeta1-stimulated cell hypertrophy was ameliorated by rhein. It was observed that TGFbeta1 not only increased the production of FN and 3H]proline incorporation in LLC-PK1 cells (P < 0.01), but also enhanced the mRNA expression of collagen IV and FN. Rhein significantly decreased the protein production and mRNA expression of ECM in LLC-PK1 cells stimulated by TGFbeta1. CONCLUSION: Rhein can inhibit cell hypertrophy and ECM accumulation in LLC-PK1 cells induced by TGFbeta1, which may partly account for the role of rhein in preventing and retarding the progression of diabetic nephropathy.