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目的:观察大黄酸对TGFβ_1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TGFβ_1(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:TGFβ_1(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。TGFβ_1也能明显增加LLC-PK1细胞[~H]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增加,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TGFβ_1诱导的近端肾小管上皮细胞肥大,抑制TGFβ_1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。
OBJECTIVE: To observe the effect of rhein on renal hypertrophy and extracellular matrix induced by TGFβ_1 in proximal tubular epithelial cells. METHODS: LLC-PK1 cells were stimulated with TGFβ_1 (2 μg/L) in vitro to induce increased cell hypertrophy and extracellular matrix synthesis. At the same time, cells were treated with different concentrations of rhein, and cell volume, protein content, and [~3H]leucine incorporation were examined to observe changes in cellular hypertrophy. In addition, cell growth (FN) content in cell culture supernatants was examined. [~3H]Proline Incorporation and Cellular Collagen IV and FN mRNA Expression to Observe the Effect of Rhein on Extracellular Matrix. RESULTS: TGFβ_1 (2 μg/L) stimulation could lead to cell hypertrophy in LLC-PK1 cells. The cell volume, intracellular protein content and [~3H]leucine incorporation were significantly increased. Rhein treatment reduced cell volume and intracellular protein. TGFβ_1 can also significantly increase [-H]proline incorporation in LLC-PK1 cells, FN content in culture supernatant, and intracellular collagen IV and FN mRNA expression. Rhein can inhibit the increase of the synthesis of the above-mentioned extracellular matrix and significantly reduce intracellular levels of collagen IV and FN mRNA. CONCLUSION: Rhein can reverse TGFβ 1 -induced proximal tubular epithelial cell hypertrophy and inhibit TGFβ 1 -stimulated extracellular matrix synthesis. This may be one of the mechanisms by which rhein inhibits or improves diabetic nephropathy and delays the progression of diabetic nephropathy.