大黄酸抑制TGF-β1诱导的肾小管上皮细胞肥大及细胞外基质产生  

The effect of rhein on the hypertrophy of renal tubular epithelial cell and accumulation of extracellular matrix induced by transforming growth factor β

作　　者：郭啸华 刘志红[1,2] 戴春笋 李恒[1,2] 刘栋 黎磊石[1,2] 

机构地区：[1]南京大学医学院临床学院 [2]南京军区南京总医院解放军肾脏病研究所,南京210002

出　　处：《肾脏病与透析肾移植杂志》2001年第2期101-105,共5页Chinese Journal of Nephrology,Dialysis & Transplantation

摘　　要：目的 :观察大黄酸对TGF β1诱导的近端肾小管上皮细胞细胞肥大及细胞外基质 (ECM)的影响。　方法 :在体外以TGF β1(2 μg/L)刺激LLC PK1细胞 ,诱导细胞肥大和ECM合成增加。与此同时 ,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3 H 亮氨酸掺入以观察细胞肥大的变化 ;检测细胞孵育 2 4h后上清的纤维连接蛋白 (FN)含量 ,3 H 脯氨酸掺入以及细胞胶原Ⅳ及FNmRNA的表达以观察大黄酸对ECM的影响。　 结果 :TGF β1(2 μg/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3 H 亮氨酸掺入量明显增加。大黄酸处理后细胞体积及细胞内蛋白量明显降低。TGF β1也明显增加LLC PK1细胞3 H 脯氨酸掺入量、培养上清中FN含量、以及细胞内胶原Ⅳ和FNmRNA的表达。大黄酸则抑制上述ECM合成的增加 ,明显降低细胞内胶原Ⅳ ,FNmRNA表达水平。　 结论 :大黄酸可以逆转TGF β1诱导的近端肾小管上皮细胞肥大 ,抑制TGF β1刺激的ECM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 investigate the effects of rhein on the hypertrophy of proximal tubular epithelial cell and the accumulation of extracellular matrix(ECM). Methodology:LLC PK1 cells (representing proximal tubular epithelial cells)were incubated with TGF β1(2 μg/L)for 24 hours to induce the hypertrophy of cells and the accumulation of ECM.The cellular volume,protein contents and 3H Leucine incorporation were evaluated as quantitative indices for measuring the cellular hypertrophic volume changes 3H proline incorporation,fibronectin (FN) content in medium and mRNA expression of collagen Ⅳ and FN were determined to identify the accumulation of ECM. Results:TGF β1 could induce significant increase of cellular volume(535 9±28 6 vs 466 2±27 5 in control group, P <0 05, n =4),cellular protein content(3 74±0 77 μg/10 4 cell vs 1 8±0 28 μg/10 4 cell in control group, P <0 05, n =4)and 3H Leucine incorporation( 20 946 ± 2 965 dpm/10 4 cell vs 7 080 ±689 dpm/10 4 cell in control group, P <0 05, n =4)as well as FN secretion (21 3±0 8 vs 10 7±1 4 ng/μg protein,in control group, P <0 05, n =4),and enhanced mRNA expression of collagen Ⅳ and FN in LLC PK1 cells.These abnormalities were markedly restrained by using the rhein(25 mg/L)comparing with that by TGF β treated group.The LLC PK1 cells showed the cellular hypertrophy(cellular volume 482 4±35 9,protein content 1 89±0 27 μg/10 4, 3H Leucine incorporation 11 500 ± 1 024 dpm/10 4 cell,respectively, P <0 05 vs TGF β1 treated group, n =4),and the ECM accumulation(the decrease of 3H proline incorporation and FN secretion as well as the inhibition mRNA expression of collagen Ⅳ and FN). Conclusion:Rhein can inhibit the hypertrophy of renal

关 键 词：大黄酸 肾小管上皮细胞肥大 转化生长因子-Β1 细胞外基质 

分 类 号：R285.5[医药卫生—中药学]