大黄酸对人肾小球系膜细胞功能的影响

Effects of rhein on the function of human mesangial cells in high glucose environment

目的 探讨大黄酸防治糖尿病肾病的作用机制。方法 用细胞培养、ELISA、明胶酶谱及免疫沉淀、Westernblot等技术 ,研究了大黄酸对肾小球系膜细胞转化生长因子 (TGFβ1 )、基质金属蛋白酶 2 , 9(MMP 2和MMP 9)及p38活化丝裂原活化蛋白激酶 (p38MAPK)活性的作用。结果 大黄酸可显著抑制肾小球系膜细胞的增殖 ,对抗高糖诱导肾小球系膜细胞TGFβ1 活性升高的作用 ;对高糖诱导肾小球系膜细胞MMP 2 ,MMP 9,pro MMP 2及pro MMP 9的活性增加无明显影响 ,但可明显对抗高糖引起的肾小球系膜细胞p38MAPK活性增加。结论 大黄酸减少FN的分泌可能与其降低p38MAPK及TGFβ1 活性有关。

Aim To study the mechanisms of anti-diabetic nephropathy of rhein on cultured human mesangial cells (HMCs). Methods To mimic the hyperglycemic (HG) environment of diabetic nephropathy, 30 mmol·L -1 glucose were added to 10% FBS RPMI 1640. The HMCs were treated with rhein for 8, 24, 48 or 72 h, at these time, the bioactivity, total activity of transforming growth factor-beta 1 (TGFβ 1), activity of p38MAPK (p38 mitogen-activated protein kinases, by using immunoprecipitate and Western blot), MMP-2 (matrix metalloproteinase-2), and MMP-9 (matrix metalloproteinase-9, by using gelatinase zymography) and the proliferation of HMCs in high glucose media were measured. Meanwhile the levels of secretion of FN in cultured HMCs were measured. Results The results showed that rhein markedly inhibit the proliferation of HMCs, significantly reduce the bioactivity of TGFβ 1 and FN secretion in HMCs, and decrease the increased activity of p38MAPK, but showed no action on the activities of MMP-2 and MMP-9. Conclusion Rhein reduced the secretion of FN and inhibited the proliferation of HMCs may through inhibiting the bioactivities of TGFβ 1 and p38MAPK.