| 钱盈盈,谢祥成,杨秀,钱红萍,王鸣,章炜.松弛素对马兜铃酸诱导的肾小管上皮细胞MMP9/TIMP1表达的影响[J].浙江中西医结合杂志,2020,30(11): |
| 松弛素对马兜铃酸诱导的肾小管上皮细胞MMP9/TIMP1表达的影响 |
| Effect of relaxin on aristolochic acid-induced expression of MMP9/TIMP1 in renal tubular epithelial cells |
| 投稿时间：2020-05-10 修订日期：2020-09-27 |
| DOI： |
| 中文关键词: 肾小管上皮细胞 马兜铃酸肾病 松弛素 细胞外基质 基质金属蛋白酶 |
| 英文关键词:Renal tubular epithelial cells, Aristolochic acid nephropathy, Relaxin, Extracellular matrix, Matrix metalloproteinase |
| 基金项目: |
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| 中文摘要: |
| 目的：探讨松弛素（RLX）对马兜铃酸诱导的肾小管上皮细胞（HK-2细胞）分泌细胞外基质、细胞基质金属蛋白酶-9（MMP9）和金属蛋白酶组织抑制因子-1（TIMP1）表达的影响。方法：体外培养人近端肾小管HK-2细胞，根据是否给予马兜铃酸刺激及RLX干预随机分为对照组（无干预）、马兜铃酸组（马兜铃酸10ug/mL刺激48h）、松弛素组（松弛素10ng/mL干预48h）、RLX+马兜铃酸组（RLX 10ng/mL干预48h后再给予马兜铃酸10ug/mL刺激48h）。ELISA法检测各组细胞上清中Ⅳ型胶原、纤连蛋白的表达。免疫印迹技术检测细胞MMP9、TIMP1蛋白的表达。结果：与对照组比较，马兜铃酸组HK-2细胞分泌Ⅳ型胶原[（87.62±4.46） ng/mL 比（26.80±0.59）ng/mL，P<0.05）]、纤连蛋白水平增加[（53.86±0.62）ng/mL 比（23.06±0.18 ）ng/mL，P<0.05）]，TIMP1表达上调[相对表达量为（3.72±0.33）比（1.00±0.11），P<0.05]，MMP9表达下降[相对表达量为（0.39±0.00）比（1.00±0.23），P<0.05]。RLX可降低马兜铃酸组细胞Ⅳ型胶原[（47.32±0.68） ng/mL 比（87.62±4.46）ng/mL，P<0.05）]、纤连蛋白 [（37.61±2.38）ng/mL比（53.86±0.62） ng/mL，P<0.05）] 水平。同时，和非治疗组相比，RLX治疗组TIMP1表达下降[相对表达量为（2.04±0.15）比（3.72±0.33），P<0.05]，MMP9表达升高[相对表达量为（0.71±0.02）比（0.39±0.00），P<0.05]。结论：RLX可改善马兜铃酸诱导的细胞外基质的失衡，促进细胞外基质的降解。作用机制可能与下调TIMP1 表达及上调MMP9表达有关。 |
| 英文摘要: |
| Objective:To explore the effects of relaxin (RLX) on the secretion of extracellular matrix, matrix metalloproteinases-9 (MMP9) and tissue inhibitor of metalloproteinases-1 (TIMP1) in HK-2 cells induced by aristolochic acids. Methods: Human proximal tubular HK-2 cells were cultured. Cells were randomly grouped into the control (no stimulation), the aristolochic acids stimulation (10ug/mL for 48 hours), and the RLX + aristolochic acids stimulation (RLX 10ng/mL for 48 hours before aristolochic acids stimulation). ELISA was used to detect the expression of type IV collagen and fibronectin in cell supernatants. Western blotting was used to determine the expression of MMP9 and TIMP1 protein. Results: Compared with those of the control group, the levels of type IV collagen (87.62±4.46 ng/mL vs. 26.80±0.59 ng/mL, P<0.05) and fibronectin (53.86±0.62 ng/mL vs. 23.06±0.18 ng/mL, P<0.05) were found significantly increased in aristolochic acid stimulated HK-2 cells (P<0.05). The relative expression of TIMP1 was markedly increased (3.72±0.33 vs. 1.00±0.11, P<0.05), while the relative expression of MMP9 was decreased (0.39±0.00 vs. 1.00±0.23, P<0.05) after aristolochic acids stimulation. RLX application ameliorated the increase of type IV collagen (47.32±0.68 ng/mL vs. 87.62 ±4.46 ng/mL, P<0.05) and fibronectin (37.61±2.38 ng/mL vs. 53.86 ±0.62 ng/mL, P<0.05) induced by aristolochic acids. Meanwhile, the relative expression of TIMP1 decreased (2.04±0.15 vs. 3.72±0.33, P<0.05) and the relative expression of MMP9 increased (0.71±0.02 vs. 0.39±0.00, P<0.05) in the RLX-treated group compared with that in the non-treatment group in HK-2 cells after aristolochic acids stimulation. Conclusion: RLX can attenuate the imbalance of extracellular matrix induced by aristolochic acids and promote the degradation of extracellular matrix. The underlying mechanism may be related to the down-regulation of TIMP1 expression and the up-regulation of MMP9 expression. |
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