| 摘要: |
| ［摘要］ 目的 探讨Rho激酶信号通路通过线粒体途径介导高尿酸血症肾小管的氧化损伤和凋亡的相关机制。方法 将人类肾小管上皮细胞（HK-2细胞）分为6组：NC组（正常对照）、转化生长因子-β1（TGF-β1）组、尿酸组（予高尿酸刺激干预）、法舒地尔（fasudil）组（予ROCK抑制剂）、ROCK1 siRNA组（予ROCK1基因沉默干预）、sc-siRNA组（阴性对照）。通过Western blot和实时荧光定量聚合酶链反应的方法检测各组细胞线粒体相关蛋白的表达水平并进行比较。结果 高尿酸显著上调HK-2细胞肌球蛋白磷酸酶靶亚基1（MYPT1）的表达，提示Rho激酶活性增加。高尿酸上调HK-2细胞锰超氧化物歧化酶2（MnSOD2）的mRNA表达水平，而fasudil的预处理则显著抑制了这一变化。转染ROCK1 siRNA后HK-2细胞MnSOD2 mRNA表达水平显著降低。Rho激酶通路对线粒体动力蛋白和生物合成基因的调节也影响了细胞的凋亡过程。结论 Rho激酶可能通过调节线粒体氧化损伤与细胞凋亡来促进高尿酸血症肾病的进展。 |
| 关键词: Rho激酶 高尿酸血症肾病 线粒体途径 氧化损伤 细胞凋亡 |
| DOI：10.3969/j.issn.1674-3806.2025.12.03 |
| 分类号:R 692 |
| 基金项目:国家自然科学基金项目（编号：82160135） |
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| Rho kinase signaling pathway mediates high uric acid-induced oxidative damage and apoptosis of renal tubular cells by regulating mitochondrial dynamin and biosynthesis related genes |
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LI Jiachang1, MA Yuhan2, WEI Jiali1
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1.Department of Nephrology, Hainan General Hospital of Hainan Medical University(Hainan General Hospital), Haikou 570311, China; 2.PSB Academy, Singapore City 159966, Singapore
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| Abstract: |
| ［Abstract］ Objective To explore the related mechanisms of oxidative damage and apoptosis of renal tubules in hyperuricemia mediated by the Rho kinase signaling pathway via the mitochondrial pathway. Methods Human renal tubular epithelial cells(HK-2 cells) were divided into 6 groups: NC group(normal control), transforming growth factor-β1(TGF-β1) group, uric acid group(intervention with high uric acid stimulation), fasudil group［receiving Rho-associated protein kinase(ROCK) inhibitor］, ROCK1 siRNA group(intervention with ROCK1 gene silencing), sc-siRNA group(negative control). The expression levels of mitochondrial-related proteins in the cells of each group were detected by using Western blot and quantitative real-time polymerase chain reaction(qRT-PCR), and the expression levels were compared among different groups. Results High uric acid significantly upregulated the expression of myosin phosphatase-targeting subunit 1(MYPT1) in HK-2 cells, suggesting an increase in Rho kinase activity. High uric acid upregulated the expression level of manganese superoxide dismutase 2(MnSOD2) mRNA in HK-2 cells, while the pretreatment with fasudil significantly inhibited this change. After transfection with ROCK1 siRNA, the expression level of MnSOD2 mRNA in HK-2 cells was significantly decreased. The regulations of mitochondrial dynamin and biosynthesis genes via the Rho kinase pathway also affected the apoptosis process of the cells. Conclusion Rho kinase may accelerate the progression of hyperuricemic nephropathy by regulating mitochondrial oxidative damage and apoptosis. |
| Key words: Rho kinase Hyperuricemic nephropathy Mitochondrial pathway Oxidative damage Apoptosis |
