吡咯烷二硫代氨基甲酸盐对白介素18诱导肾小球系膜细胞增殖及细胞外基质分泌的影响

Effect of PDTC on IL-18-induced proliferation and extracellular matrix secretion of glomerular mesangial cells

目的观察吡咯烷二硫代氨基甲酸盐(PDTC)对白介素18(IL-18)诱导肾小球系膜细胞(MC)增殖及细胞外基质(ECM)分泌的影响及机制。方法 MTT法检测MC的增殖情况,ELISA检测Ⅳ型胶原蛋白(CO-Ⅳ)和层黏连蛋白(LN),免疫细胞化学检测核转录因子-κB(NF-κB)P65的核易位。结果高糖环境下,25μg/L、50μg/L的IL-18作用48h能明显促进MC增殖、CO-Ⅳ和LN的分泌(P<0.01),使NF-κB P65激活,50μg/L组更为显著(P<0.01)。100μmol/L的PDTC能显著抑制IL-18诱导MC增殖作用(P<0.01),CO-Ⅳ和LN的分泌以及P65核易位。结论 PDTC可能通过NF-κB P65途径抑制IL-18诱导的MC增殖和细胞外基质分泌。

Objective To study the effects of PDTC on the IL-18 induced proliferation and extracellular matrix secretion of glomerular mesangial ceils （MC）, and to make clear the possible mechanism. Methods Glomerular mesangial cells proliferation was assessed by MTT colormetric assay and the type Ⅳ collagen （CO-Ⅳ）and laminin（LN） were determined by ELISA. The expression of nuclear transcription factor of Kappa B（NF-κB）subunit p65 was evaluated by immuncytochemistical method. Results At the concentration of 25μg/L and 50μg/L, IL-18 markedly induced MC proliferation and CO- Ⅳ and LN secretion at 48h incubation compared with control group （P〈0.01）, which could be markedly inhibited by PDTC（100μmol/L）（P〈0.01）. The activation of NF-κB by IL-18 was suppressed by PDTC markedly. Conclusions IL-18 could induce MC proliferation and type Ⅳ collagen and laminin secretion, which could be inhibited by PDTC via NF-κB.