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低密度脂蛋白及氧化修饰低密度脂蛋白对人系膜细胞增殖及

2022-07-29
来源:求医网
摘要:目的观察不同浓度低密度脂蛋白(LDL)及氧化修饰低密度脂蛋白(ox-LDL)对人系膜细胞(HMC)增殖和细胞毒性作用,及对培养细胞上清Ⅳ型胶原的含量及表达Ⅳ型胶原α1链mRNA的影响。方法采用体外HMC培养,H3-thymidine掺入研究人系膜细胞增殖,LDL释放实验研究细胞毒作用,ELISA法测定Ⅳ型胶原含量和逆转录-聚合酶链反应(RT-PCR)法研究Ⅳ型胶原α1链mRNA表达。结果LDL能刺激HMC增殖;低浓度ox-LDL抑制HMC增殖,高浓度ox-LDL剂量依赖性表现细胞毒性作用;LDL和低浓度ox-LDL能通过上调HMC表达Ⅳ型胶原α1链mRNA促进其产生Ⅳ型胶原。结论LDL在引起和促进肾小球硬化的发生和发展中起一定作用,LDL氧化后,可加重该作用。

Effects of LDL and ox-LDL on human mesangial cells proliferation and mesangial matrix production

TAO Jianling ,LI Xuewang ,SU Ying,et al.

(Department of Nephrology,Peking Union Medical College Hospital,Beijing 100730,China)

Abstract:Objective To observe the effects of LDL and ox-LDL on human mesangial cells(HMC)proliferation and viability,the concentrations of collagen Ⅳ in the supernatants of cultured HMC and the expression of collagen Ⅳα1 mRNA by HMC.Methods The culture of HMC was established in vitro.Cell proliferation and viability were studied by H3-thymidine incorporation and LDH releasing test respectively.The concentration of collagen Ⅳ was measured by ELISA and the expression of collagen Ⅳα1 mRNA was examined by RT-PCR.Results HMC proliferation could be stimulated by LDL and be inhibited by ox-LDL at low concentrations.Cytotoxicity was showed by ox-LDL at high concentrations in concentration-dependent manner.Production of collagen Ⅳ by HMC could be stimulated by either LDL or ox-LDL at low concentrations via promoting HMC expression of collagen Ⅳα1 mRNA.Conclusion LDL and ox-LDL may contribute to the pathogenesis of glomerulosclerosis through influencing the mesangial cell proliferation or viability and accumulation of mesangial matrix.

Keywords:Low density lipoprotein;Collagen type Ⅳ;Glomerulosclerosis;Oxidized low density lipoprotein;Mesangial cell;参考文献:

[1]Kreisberg JI,Karnovsky MJ.Glomerular cells in culture.Kidney Int,1983,23:439-447.

[2]张林华,刘秉文.一次性密度梯度超速离心分离人血清脂蛋白.生物化学与生物物理学报.1989,21:257-260.

[3]王克勤,周凤兰,程小颖.琼脂糖凝胶电泳用于人血清β-脂蛋的分离分型.生物化学与生物物理学报.1979,11: 37-49.

[4]Moorhead JF,Chan MK,EI-Nahas M,et al.Lipid nephrotoxicity in chronic progressive glomerular and tubulointerstitial disease. Lancet,1982,2:1309-1311.

[5]Schlondorff D.Cellular mechanisms of lipid injury in the glomerulus.Am J Kidney Dis,1993,22:72-82.

[6]Kramer-Guth A,Nauck M.VLDL and LDL metabolism in human and rat mesangial cells.Nephron,1996,74:378-385.

[7]David CW,Ravinder SC,Nicholas T,et al.Oxidation of low density lipoprotein by mesangial cells may promote glomerular injury.Kidney Int,1994,45:1628-1636.

[8]Kim SB,Kang SA,Cho YJ,et al.Effects of low density lipoprotein on type Ⅳ collagen production by cultured rat mesangial cells.Nephron,1994,67:327-333.

[9]Kamanna M,Bui DT,Roh DD,et al.LDL and oxidized-LDL stimulate collagen synthesis by mesangial cells.J Am Soc Nephrol,1992,3:634.

[10]Keane WF,Kasiske BL,O’Donnell MP,et al.Oxidized low density lipoprotein increases mesangial cell expression of type Ⅳ collagen [α1(Ⅳ)] Mrna.J Am Soc Nephrol,1992:3:635.

[11]Hyun SL,Bong CK,Young Sk,et al.Involvement of oxidation in LDL-induced collagen gene regulation in mesangial cells.Kidney Int,1996,50:1582-1590.

收稿日期:1998-12-24