洛伐他丁对大鼠肾小球系膜细胞增殖的影响

Effect of lovastatin on proliferation of cultured rat mesangial cells

目的 研究他丁类降脂药物对肾小球系膜细胞增殖的影响。方法 应用羟甲基戊二酰辅酶A（HMG-CoA）还原酶抑制剂洛伐他丁来观察其对培养的大鼠肾小球系膜细胞增殖的影响。用含有或没有洛伐他丁和甲羟戊酸及其代谢产物的10％胎牛血清或血小板源生长因子（PDGF）刺激培养的大鼠肾小球系膜细胞,然后用测定溴化脱氧尿嘧啶核苷（BrdU）的整合来评估DNA的合成并测定细胞的数量。结果 洛伐他丁对10％胎牛血清刺激系膜细胞DNA的合成抑制是剂量依赖性,并且能够抑制细胞的生长。甲羟戊酸,焦磷酸（牛龙）牛儿基（牛龙）牛儿酯能够显著地逆转洛伐他丁的抑制作用。结论 洛伐他丁通过影响甲羟戊酸的合成抑制鼠肾小球系膜细胞的增殖,这可能为治疗系膜增殖性肾小球疾病提供一个新的方法。

Objective To investigate the effect of lovaslatin on proliferation of cultured rat mesangial cells. Methods Cultured rat mesangial cells were stimulated by 10% fetal calf serum (FCS) or platelet-derived growth factor (PDGF) in the absence or the presence of lovastain and mevalonate metabolites. 5-Bromo-2-deoxyuridine incorporation was used to assess DNA synthesis. Results FCS or PDGF caused a marked stimulation of DNA synthesis in the mesangial cells. Lovastatin inhibited FCS or PDGF-stimulated BrdU incorporation and cell proliferation. Mevalonic acid, farnesyl pyrophosphate and geranylgeranyl pyrophosphate significantly prevented inhibitory effect of lovastatin on mesangial proliferation induced by FCS. Mevalonic acid and geranylgeranyl pyrophosphate also significantly reversed inhibitory effect of lovastatin on mesangial proliferation induced by PDGF. But farnesyl pyrophosphate only partly reversed inhibitory effect of lovastatin. Conclusions Lovastatin, by inhibiting the synthesis of isoprenoid metabolites of mevalonate, can suppress mesangial cell proliferation. It is possible to provide a new approach for treatment of proliferative glomerular diseases.