Scientific Research Department, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China.
Guangxi Medical College, Nanning, Guangxi 530021, China.
Chin Med J (Engl). 2019 Mar 20;132(6):664-670. doi: 10.1097/CM9.0000000000000127.
Peritoneal fibrosis is the primary reason that patients with end-stage renal disease (ESRD) have to cease peritoneal dialysis. Peritonitis caused by Gram-negative bacteria such as Escherichia coli (E. coli) were on the rise. We had previously shown that matrine inhibited the formation of biofilm by E. coli. However, the role of matrine on the epithelial-mesenchymal transition (EMT) in peritoneal mesothelial cells under chronic inflammatory conditions is still unknown.
We cultured human peritoneal mesothelial cells (HPMCs) with lipopolysaccharide (LPS) to induce an environment that mimicked peritonitis and investigated whether matrine could inhibit LPS-induced EMT in these cells. In addition, we investigated the change in expression levels of the miR-29b and miR-129-5p.
We found that 10 μg/ml of LPS induced EMT in HPMCs. Matrine inhibited LPS-induced EMT in HPMCs in a dose-dependent manner. We observed that treatment with matrine increased the expression of E-cadherin (F = 50.993, P < 0.01), and decreased the expression of alpha-smooth muscle actin (F = 32.913, P < 0.01). Furthermore, we found that LPS reduced the expression levels of miR-29b and miR-129-5P in HPMCs, while matrine promoted the expression levels of miR-29b and miR-129-5P.
Matrine could inhibit LPS-induced EMT in HPMCs and reverse LPS inhibited expressions of miR-29 b and miR-129-5P in HPMCs, ultimately reduce peritoneal fibrosis. These findings provide a potential theoretical basis for using matrine in the prevention and treatment of peritoneal fibrosis.
腹膜纤维化是终末期肾病（ESRD）患者停止腹膜透析的主要原因。由大肠杆菌（E. coli）等革兰氏阴性菌引起的腹膜炎呈上升趋势。我们之前已经表明苦参碱抑制了大肠杆菌生物膜的形成。然而，苦参碱在慢性炎症条件下对腹膜间皮细胞上皮-间充质转化（EMT）的作用尚不清楚。
我们用脂多糖（LPS）培养人腹膜间皮细胞（HPMCs），以模拟腹膜炎环境，并研究苦参碱是否能抑制这些细胞中 LPS 诱导的 EMT。此外，我们还研究了 miR-29b 和 miR-129-5p 的表达水平变化。
我们发现 10μg/ml 的 LPS 诱导了 HPMCs 的 EMT。苦参碱以剂量依赖性方式抑制 LPS 诱导的 HPMCs EMT。我们观察到苦参碱处理增加了 E-钙粘蛋白的表达（F=50.993，P<0.01），并降低了α-平滑肌肌动蛋白的表达（F=32.913，P<0.01）。此外，我们发现 LPS 降低了 HPMCs 中 miR-29b 和 miR-129-5P 的表达水平，而苦参碱促进了 miR-29b 和 miR-129-5P 的表达水平。
苦参碱可抑制 LPS 诱导的 HPMCs EMT，并逆转 LPS 抑制的 HPMCs 中 miR-29b 和 miR-129-5P 的表达，最终减少腹膜纤维化。这些发现为苦参碱在预防和治疗腹膜纤维化中的应用提供了潜在的理论基础。
