蟾蜍灵对脂多糖诱导的大鼠肾小球系膜细胞IL-6和TGF-β1表达的影响

目的 探讨蟾蜍灵对脂多糖(LPS)诱导的大鼠肾小球系膜细胞(GMC)增殖及白细胞介素6(IL-6)和转化生长因子β1(TGF-β1)表达的影响.方法 体外培养大鼠肾小球系膜细胞,分为蟾蜍灵干预(A)组、LPS刺激(B)组和对照(C)组,应用台盼兰拒染法检测蟾蜍灵对GMC的细胞毒性作用,MTT观察LPS诱导的GMC增殖的变化,RT-PCR检测TGF-β1和IL-6 mRNA的相对表达.结果 与B组相比,A组蟾蜍灵10-8mol/L和10-7mol/L明显抑制GMC增殖,A492nm值分别为[(0.818±0.058)和(0.574±0.182),P<0.01].B组IL-6和TGF-β1 mRNA相对表达量较C组和A组明显减少(P<0.01).结论 蟾蜍灵明显抑制LPS诱导的大鼠系膜细胞增殖及其IL-6和TGF-β1的表达.     

醛固酮对肾小球系膜细胞合成分泌纤维连接蛋白的影响

目的研究醛固酮(aldosteroen,ALD)及其受体拮抗剂螺内酯(spironolactone,SPI)对大鼠肾小球系膜细胞合成分泌纤维连接蛋白(fibronectin,FN)的影响。方法以不同浓度的ALD(10-11、10-9、10-7mol/L)和/或10-7mol/L SPI刺激系膜细胞48 h后,应用酶联免疫吸附试验(ELISA)测定培养上清中FN的浓度,应用半定量反转录-聚合酶链反应(RT-PCR)检测细胞FN mRNA的表达;以10-9mol/L浓度的ALD刺激系膜细胞不同时间(24、48、72 h)后,应用ELISA测定培养上清中FN的浓度,应用半定量RT-PCR方法检测细胞FN mRNA的表达。结果ELISA结果显示,ALD促进大鼠肾小球系膜细胞合成分泌FN,且具有浓度依赖和时间依赖性的特点,SPI能够拮抗ALD的作用。半定量RT-PCR方法结果显示,ALD促进培养的大鼠肾小球系膜细胞FN mR-NA的表达,且具有浓度依赖和时间依赖性的特点,SPI能够拮抗ALD的作用。结论ALD从蛋白和基因水平促进大鼠肾小球系膜细胞合成分泌FN,且具有浓度依赖和时间依赖性的特点,SPI能够拮抗ALD的作用,从而可能有益于延缓肾小球硬化的进展。     

氟伐他汀对高糖大鼠肾小球系膜细胞转化生长因子β1的影响

目的观察高糖大鼠肾小球系膜细胞(HBZY-1)转化生长因子β1(TGF-β1)的变化以及氟伐他汀对其影响。方法体外培养HBZY-1细胞,将其分成以下几组:正常组、高糖组、甘露醇对照组、3个浓度氟伐他汀组。24 h后进行细胞形态观察,MTT法测定并计算细胞存活率和抑制率。RT-PCR法测定各组TGF-β1 mRNA的表达。Western blot法、免疫细胞化学法测定各组TGF-β1蛋白表达及分布。结果与正常组相比,HBZY-1细胞在高糖刺激下,TGF-β1 mRNA及蛋白表达明显增加(P<0.05)。与高糖组相比,氟伐他汀组TGF-β1 mRNA及蛋白表达明显减少(P<0.05)。结论高糖环境可促使HBZY-1细胞TGF-β1异常表达;而氟伐他汀可阻抑高糖对HBZY-1细胞TGF-β1的活化而发挥肾脏保护作用。     

极低密度脂蛋白对大鼠系膜细胞分泌FN以及TGFβ1mRNA转录的作用

目的观察极低密度脂蛋白对大鼠系膜细胞分泌FN以及对转化生长因子-β1(TGF-β1)基因转录的作用，进而探讨VLDL对系膜细胞的毒性作用。方法应用ELISA法测定培养细胞上清纤维连接蛋白(Fibronectin，FN)的分泌；RT—PCR法测定系膜细胞TGF-β1的基因表达情况。结果在一定的时间范围内(6～24h)，VLDL可以以时问、剂量依赖性的关系促进系膜细胞分泌FN。随着刺激时间的增加，TGF-β1。mRNA转录逐渐增强；VLDL浓度在0～500μg／ml之间时，TGF-β1 mRNA转录随着VLDL浓度的增加而逐渐增强。结论VLDL可以促进系膜细胞分泌FN以及TGF-β1的基因转录，提示VLDL具有肾脏毒性。     

脂联素对高糖环境下肾小球系膜细胞转化生长因子β1及细胞间粘附分子1表达的影响

目的研究脂联素(ADPN)对高糖培养的大鼠肾小球系膜细胞转化生长因子β1(TGF-β1)及细胞间粘附分子1(ICAM-1)表达的影响。方法以培养的大鼠HBZY-1肾小球系膜细胞(MCs)为受试对象,将MCs分为3组:正常对照组(5.5mmol/L葡萄糖,NG组),高糖组(30mmol/L葡萄糖,HG组),高糖+不同浓度的脂联素组(30mmol/L葡萄糖,2.5、5.0、7.5、10.0、15.0、20.0μg/mlADPN)分别作用48h后,用ELISA法测定细胞内TGF-β1及ICAM-1表达。结果作用48h后,高糖明显上调细胞内TGF-β1及ICAM-1表达。加入低浓度脂联素对于TGF-β1、ICAM-1表达影响不大,而随着脂联素浓度的升高,TGF-β1及ICAM-1的表达明显下降,与高糖组相比,浓度为10～20mg/L的脂联素组TGF-β1及ICAM-1的表达差异有统计学意义(P<0.05)。结论中等以上浓度的脂联素能下调TGF-β1及ICAM-1表达,提示脂联素可能通过阻抑TGF-β1及ICAM-1表达起到抗纤维化,从而发挥对糖尿病肾脏的保护作用。     

高糖环境下HGF对肾小球系膜细胞增殖及TGF-β1的影响

目的研究高糖环境下大鼠肾小球系膜细胞(RMC)的增殖、转化生长因子β1(TGF-β1)的分泌、以及肝细胞生长因子(HGF)的干预作用。方法①将RMC分为3组:正常对照组;高糖组;高糖+HGF组(25.0mmol/L葡萄糖,50ng/mlHGF)。分别培养不同时间(12,24,48,72,96h)。运用MTT法测定细胞的增殖情况。②将RMC分为3组:正常对照组;高糖组;甘露醇对照组:(20.0mmol/L甘露醇)。分别于培养的12、24、48、96h收集细胞及上清夜,用ELISA法来检测TGF-β1分泌量。③将RMC分为:正常对照组;高糖组;高糖+HGF组(HGF浓度分别为25、50、100、200ng/ml)。分别培养48h后,用ELISA法测定此时TGF-β1分泌情况。以上各组正常组中葡萄糖浓度5.5mmol/L,高糖浓度25.0mmol/L。结果①25.0mmol/L高糖在24h促进RMC增殖,肝细胞生长因子(HGF)可以抑制细胞增殖。在48,72和96h高糖抑制细胞增殖。HGF对抗高糖对细胞增殖的抑制作用;而且呈时间依赖性。②高糖促进TGF-β1分泌,HGF可以抑制TGF-β1的分泌,且呈剂量依赖性。结论高糖刺激肾小球系膜细胞TGF-β1出现稳定高表达,而给予外源性的HGF后,系膜细胞TGF-β1的分泌减少,而且呈时间依赖性。     

TGF-β/Smad信号通路对肾小球系膜细胞COX-2表达的影响

目的 探讨转化生长因子β(TGF-β)/Smad信号通路对肾小球系膜细胞环氧化酶2(COX-2)表达的影响.方法 取传代培养第4代系膜细胞进行分组:对照组(A组)、TGF-β 5 ng/ml组(B组)、TGF-β 10 ng/ml组(C组)、TGF-β 10 ng/ml+N5-398 10 μmol(D组)和TGF-β10 ng/ml+staurosporine 5 nmol/ml组(E组).用RT-PER方法测定各组COX-2 mRNA及Smad 2 mRNA的表达,Western blot法测定各组COX-2及Smad 2蛋白的表达.结果 不同浓度TGF-β作用4、12、24 h后,系膜细胞Smad 2 mRNA和COX-2 mRNA表达及二者的蛋白表达均增加,且呈浓度和时间依赖性(P<0.05),加入COX-2抑制剂NS-398或Smad 2抑制剂staurosporine后,COX-2和Smad 2的表达均减少(P<0.05).COX-2和Smad 2表达呈正相关(r=0.9438,P<0.05).结论 TGF-β可通过Smad信号通路刺激肾小球系膜细胞COX-2的表达.     

LOX-1在ox-LDL诱导人肾小球系膜细胞表达TGF-β1中的作用

为探讨血凝素样氧化低密度氧化脂蛋白受体(LOX-1)在氧化低密度脂蛋白(ox-LDL)诱导人肾小球系膜细胞(HGMCs)表达TGF-β1中的作用,在体外培养人肾小球系膜细胞,在不同的时间加入不同浓度的ox-LDL及LOX-1阻滞性抗体JTX92,以酶联免疫吸附法(ELISA)检测细胞培养液中转化生长因子(TGF-β1)浓度,用半定量RT-PCR检测细胞LOX-1和TGF-β1mRNA表达,用Western印迹检测细胞LOX-1和TGF-β1蛋白合成。结果表明,ox-LDL以时间和浓度依赖的方式增加LOX-1表达的同时,也以时间和浓度依赖的方式增加细胞内TGF-β1mRNA表达、蛋白合成及培养液中TGF-β1的含量;JTX92(10μg/ml)可以明显抑制LOX-1和TGF-β1的表达(两者P<0·01)。结论:ox-LDL通过激活LOX-1调节HGMCs TGF-β1基因表达、蛋白的合成与分泌。     

普罗布考对高糖培养的大鼠肾小球系膜细胞增殖及转化生长因子-β1的影响

目的探讨普罗布考（probucol,PRB）对高糖培养的大鼠肾小球系膜细胞（rat mesangial cells,RMCs）增殖及转化生长因子-β1（TGF-β1）的影响。方法①将RMCs分为正常对照组（葡萄糖5．5mmol·L^-1）、高糖组（葡萄糖30．0mmol·L^-1）、高糖＋不同浓度PRB纽（葡萄糖30．0mmol·L^-1＋10、20、50μmol·L^-1PRB）,MTT法检测培养24、48、72h后细胞的增殖情况,ELISA法检测培养24h后TGF-β1分泌量。②将RMCs分为正常对照组（葡萄糖5．5mmol·L^-1）、渗透浓度对照组（5．5mmol·L^-1葡萄糖＋24．5mmol·L^-1甘露醇）、高糖组（葡萄糖30．0mmol·L^-1）、高糖＋20μmol·L^-1PRB组,ELISA法检测培养12、24、48、72h后TGF-β1分泌量。结果①培养24h后,高糖刺激RMCs增殖,PRB呈时间依赖性和剂量依赖性地抑制RMCs的增殖（P〈0．05）。②高糖刺激24h后,TGF-β1分泌量增多,PRB能抑制高糖诱导的TGF-β1,分泌（P〈0．05）。结论PRB可能通过抑制肾小球系膜细胞TGF-β1的分泌,抑制高糖条件下大鼠肾小球系膜细胞的增殖,发挥肾脏保护作用。     

脂联素对脂肪细胞条件培养基促系膜细胞合成转化生长因子β1的作用

目的 探讨脂联素对脂肪细胞条件培养基促系膜细胞(MsMC)合成转化生长因子β1(TGFβ1)的作用.方法 将MsMC分为7组:A组加入无血清DMEM培养基;B组加入脂肪细胞条件培养基;C组加入pSuper质粒转染后条件培养基;D组加入pcDNA3.1(-)质粒转染后条件培养基;E组加入脂联素siRNA-pSuper表达质粒转染后条件培养基;F组加入脂联素pcDNA3.1(-)表达质粒转染后条件培养基;C组加入添加3 mg/L脂联素的脂肪细胞条件培养基.用脂联素pcDNA3.1(-)表达质粒、脂联素siRNA-pSuper表达质粒、pcDNA3.1(-)质粒及pSuper质粒分别转染3T3-L1细胞(脂质体2000转染法),诱导细胞分化为成熟脂肪细胞后收集细胞,以蛋白质印迹法检测细胞裂解液中脂联素蛋白含量.孵育MsMC 9 h后,收取细胞,用实时定量聚合酶链反应检测细胞裂解液中TGFβ1 mRNA水平;孵育24 h后收取上清液,用酶联免疫吸附试验检测上清液中TGFβ1蛋白质水平.结果 与未转染的成熟脂肪细胞比较,用脂联素pcDNA3.1(-)表达质粒转染3T3-L1细胞得到的成熟脂肪细胞的细胞裂解液中脂联素含量增加[(0.59±0.06)比(0.21±0.02)],差异有统计学意义(P＜0.05);用脂联素siRNA-pSuper表达质粒转染3T3-L1细胞得到的成熟脂肪细胞的细胞裂解液中脂联素含量减少[(0.12±0.01)比(0.39±0.02)],差异有统计学意义(P＜0.05).B组TGFβ1 mRNA水平及蛋白质表达含量高于A、F、G组[TGFβ1 mRNA:(3.09 ±0.15)比(1.50±0.35)、(2.1±0.53)、(1.8±0.42),TGFβ1蛋白质水平:(708±10)比(224±16)、(382±11)、(300 ±25)],差异有统计学意义(P＜0.05).结论 脂肪细胞条件培养基可刺激系膜细胞合成TGFβ1,而脂联素对这一效应具有明显抑制作用.     

肾小球系膜细胞增殖抑制的研究进展

肾小球系膜细胞异常增殖对肾小球疾病进展有重要作用,探讨其发生机制对肾小球疾病的防治具有重要意义.本文综述了近年来肾小球系膜细胞增殖机制及抑制因子的研究进展.     

白花丹素抑制肾小球系膜细胞增殖及促纤维化相关因子的表达

目 的：探讨白花丹素对人肾小球系膜细胞株HMC细胞增殖及TGFβ1、CTGF、FN表达的影响。 方 法： 1 μmol/L~10 μmol/L白花丹素分别处理HMC细胞后,MTT法检测细胞增殖活性;RT-PCR和细胞免疫荧光法分别检测TGFβ1、CTGF、FN mRNA和蛋白的表达。 结 果：1 μmol/L~10 μmol/L白花丹素作用后,HMC细胞呈时间、浓度依赖性生长抑制,TGFβ1、CTGF、FN mRNA和蛋白的表达下降。 结 论： 白花丹素通过降低HMC细胞TGFβ1、CTGF、FN的表达,抑制HMC细胞增殖。     

肾舒胶囊对阿霉素肾病大鼠系膜的影响

目的探讨肾舒胶囊对阿霉素肾病（AN）大鼠系膜细胞增殖、系膜基质增多的影响及其机制。方法将雄性wistar大鼠36只随机分至正常对照组（N组）、非治疗组（M组）、肾舒胶囊治疗组（S组）,采用单次尾静脉注射阿霉素建立AN模型,研究肾舒胶囊对AN大鼠24h尿蛋白排泄率、血清总蛋白（TP）、白蛋白（ALB）、总胆固醇（TC）、甘油三酯（TG）、血浆内皮素（ET）、降钙素基因相关肽（CGRP）等的影响。自动图像分析仪测定各组肾小球的定量指数、系膜基质指数;用免疫组化法观察肾组织增殖性细胞核抗原的表达。结果与M组比,S组大鼠24h尿蛋白排泄率第7d始明显降低（P〈0.05,P〈0.01）,4周末血清TP、ALB升高（P〈0.05）,TC、TG降低（P〈0.05）,降钙素基因相关肽（CGRP）升高（P〈0.01）,血浆内皮素（ET）降低（P〈0.01）,24h尿蛋白排泄率明显下降（P〈0.05）,系膜面积显著减少（P〈0.05）,PCNA阳性细胞数减少（P〈0.05）。结论肾舒胶囊具有调整ET和CGRP的病理性改变,改善或修复病理性改变,减少系膜基质的增多及系膜细胞的增殖,从而对AN肾病大鼠具有保护作用。     

益肾蠲湿合剂对肾小球系膜细胞增殖及细胞外基质分泌的影响

目的观察益肾蠲湿合剂对肾小球系膜细胞（GMC）增殖及细胞外基质的抑制作用。方法将含低、中、高剂量益肾蠲湿合剂的药物血清作用于10％血清-DMEM培养液培养的GMC,分别用噻唑蓝和酶联免疫吸附（ELISA）方法检测细胞增殖和培养液中基质的浓度。结果益肾蠲湿合剂对GMC增殖有明显的抑制作用,并随着剂量的增加作用也逐渐增强（72h低、中、高剂量的抑制率分别为28．3％、40．5％、47．5％）。同时益肾蠲湿合剂对GMC分泌细胞外基质有也明显的抑制作用（高剂量组对FN、LN及ColⅣ的抑制率分别为26．1％、25．4％、22．3％,中剂量组分别为17．4％、20．5％、15．9％;低剂量组分别为10．4％、10．7％、9．3％）。结论益肾蠲湿合剂对GMC的增殖及基质的分泌有明显的抑制作用,这可能是其有效抑制各种慢性肾炎发展的重要原因。     

Regulation of glomerular mesangial cell proliferation in culture by adrenomedullin.

Adrenomedullin is a recently discovered vasodilatory peptide that has been shown to be a potent activator of adenylate cyclase in a variety of cell systems, including rat mesangial cells. The major aim of the present study was to determine the regulation of rat mesangial cell proliferation (using [3H]thymidine incorporation as an index), apoptosis (using nucleosome-associated cytoplasmic DNA fragmentation as an index) and mitogen-activated protein kinase (MAPK) cascade, specifically extracellular signal-regulated kinase (ERK), jun-amino terminal kinase (JNK) and P38 mitogen-activated protein kinase (P38 MAPK) activities, by adrenomedullin-stimulated cyclic AMP-protein kinase-A pathway. Adrenomedullin increased cAMP levels significantly above basal and the response was inhibited by the adrenomedullin receptor antagonist, adrenomedullin-(22-52). Adrenomedullin also decreased [3H]thymidine incorporation and increased nucleosome-associated cytoplasmic DNA fragmentation, in a concentration-dependent fashion. Both these responses were receptor mediated as, adrenomedullin-(22-52) inhibited these effects. The decrease in proliferation and increase in apoptosis were both mimicked by forskolin, a direct adenylate cyclase activator. Adrenomedullin-mediated decrease in proliferation and increase in apoptosis were inhibited by H89 [[N-[2-((p-bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide, hydrochloride]], a potent protein kinase-A inhibitor. Associated with the changes in proliferation and apoptosis, adrenomedullin decreased ERK2 activity, and increased JNK1 and P38 MAPK activities. All these kinase activities, except the increase in JNK1 activity could be simulated using forskolin. In addition, only adrenomedullin-mediated changes in ERK2 and P38 MAPK activities were inhibited by H89 while, adrenomedullin-stimulated JNK1 was not consistently inhibited by the protein kinase-A inhibitor. These results suggest that adrenomedullin might play an important role in mesangial cell turnover and that although adrenomedullin-mediated responses are primarily cAMP-dependent, it does not preclude the involvement of cAMP-independent pathways.     

Effect of nanoparticles on digitoxin uptake and pharmacologic activity in rat glomerular mesangial cell cultures

Our experiments analyzed the uptake of free and nanoparticles (NP)-associated digitoxin (DGT) by rat glomerular mesangial cells. NP were prepared by the nanoprecipitation method using the biodegradable polyester, polycaprolactone (PCL). Prior to in vitro experiments, the systems were characterized by means of spectrofluorimetry, dynamic light scattering, and size exclusion chromatography (SEC). The loading efficiency was 80.30 +/- 1.03% of the initial DGT amount in the preparation, and the average particle size was 176 +/- 8 and 161 +/- 6 nm for DGT-NP and "empty" NP, respectively. SEC studies revealed noncovalent interactions among the different chemical compounds in the formulation. In vitro experiments were conducted at 37 degrees C and pH 7.5 by incubating "empty" NP, free DGT or DGT-NP (10 microg PCL/mL; 100 ng DGT/mL) with glomerular mesangial cells for 30 and 60 min. Uptake of DGT by the cells was favored by its incorporation into PCL-NP and showed time dependency. After 30 min of incubation, no significant differences of drug uptake were seen between free DGT (13.1 +/- 2.8%) or DGT-NP (17.4 +/- 4.9%); however, the uptake of DGT, when it was associated to the polymeric carrier, increased by approximately 2-fold (37.8 +/- 5.7%) at 60 min, whereas no significant changes were observed for free drug (20.0 +/- 6.8%). The pharmacologic activity of the drug was evaluated by measuring the planar cell surface area (PCSA). "Empty" NP, free drug, or DGT-NP did not produce significant variations on the PCSA as compared with control cells after a 30-min incubation. Nonetheless, DGT-NP reduced the PCSA to 82.51 +/- 8.42% of control values when the incubation lasted 60 min. The ability of cells to exclude the trypan blue dye and the leakage of lactate dehydrogenase into the medium revealed no signs of increased toxicity from incorporation of DGT into PCL-NP. Therefore, PCL-NP improved drug uptake by the cells without altering the pharmacologic activity and toxicity of the drug. Thus, they can be a useful approach to target drugs to the kidneys or the heart.     

Modulation of cell proliferation and hypertrophy by gangliosides in cultured human glomerular mesangial cells

Glomerular mesangial cells (GMCs) in diverse renal diseases undergo cell proliferation and/or hypertrophy, and gangliosides have been reported to play an important role in modulating cell structure and function. This study compared the effects of transforming growth factor-beta1 (TGF-beta1) and the effects of the application of exogenous gangliosides on GMCs and investigated whether the application of exogenous gangliosides regulated cellular proliferation and hypertrophy. Human GMCs were cultured with exogenous gangliosides and TGF-beta1 in a media containing 10% fetal bovine serum and in a media without the fetal bovine serum. Exogenous gangliosides biphasically changed the proliferation of human GMCs (0.1-1.0 mg/mL). A low concentration (0.1 mg/mL) of gangliosides mainly increased the number of human GMCs, whereas cellular proliferation was significantly reduced by raising the concentration of exogenous gangliosides. TGF-beta1 greatly reduced the number of human GMCs in a concentration-dependent manner (1-10 ng/mL). Serum deprivation accelerated the gangliosides- and TGF-beta1-induced inhibition of mesangial cell proliferation to a greater extent. Gangliosides (1.0 mg/ mL) and TGF-beta1 (10 ng/mL) both caused a significant increase in the incorporation of [3H]leucine per cell in the serum-deprived condition, whereas it was completely reversed in serum-supplemented condition. Similar results to the [3H]leucine incorporation were also observed in the changes in cell size measured by flow cytometric analysis. These results show that exogenous gangliosides modulate cell proliferation and hypertrophy in cultured human GMCs, and these cellular responses were regulated differently based on whether the media contained serum or not. Results from the present study raise new possibilities about the potential involvement of gangliosides in the development of mesangial cell proliferation and hypertrophy.     

过表达SOCS2对人肾小球系膜细胞中炎性因子表达的影响及其机制研究

目的 建立过表达SOCS2的HMCs细胞模型,检测各组HMCs中JAK/STAT信号通路的活性,观察DN炎性因子的表达,明确过表达SOCS2对细胞模型的影响及作用机制。方法 通过腺病毒感染的方法使细胞模型中过表达SOCS2,实验分为CG组、CG+Ad-null组、CG+Ad-SOCS2组、HG组、HG+Ad-null组、HG+Ad-SOCS2组。Western blot方法检测各组细胞模型中JAK/STAT信号通路的活化情况。ELISA方法检测各组细胞培养上清中IL-6、TNF-α的表达。结果 与CG组相比,高糖诱导后的HG组、HG+Ad-null组、HG+Ad-SOCS2组中p-JAK2、P-STAT3、IL-6、TNF-α的表达量均升高(P<0.01);与HG组相比,HG+Ad-SOCS2组中这些指标均显著下降(P<0.01),而HG+Ad-null组则无显著差异。结论 SOCS2通过抑制JAK/STAT信号通路来降低细胞模型中炎性因子IL-6、TNF-α的表达。     

普伐他汀联合二甲双胍对大鼠肾小球系膜细胞增殖的影响

目的 探讨普伐他汀联合二甲双胍对肾小球系膜细胞（GMC）增殖的影响.方法 通过体外培养GMC,用高浓度葡萄糖刺激GMC增殖,选择最佳刺激浓度,并在普伐他汀联合二甲双胍不同剂量的条件下,比较GMC在不同剂量、不同时间的增殖情况.结果 葡萄糖最佳刺激浓度为0.6 g/L;普伐他汀联合二甲双胍高剂量组对葡萄糖刺激的GMC增殖抑制作用最明显,与低剂量组比较差异有统计学意义（P〈0.05）,但与中剂量组比较差异无统计学意义（P〉0.05）.结论 普伐他汀联合二甲双胍对GMC增殖具有抑制作用,可治疗糖尿病肾病.     

Protective effects of polyphenols against cadmium-induced glomerular mesangial cell myocontracture

The main objective of this work was to determine the ability of polyphenols (procyanidoloic oligomers; PCO) to diminish the contracture of CdCl₂-induced mesangial cells (smooth muscle cell type). Glomeruli were isolated by passing rat renal cortex pulp through calibrated sieves followed by a culture step for outgrowth of cells. PCO lethality was measured by microassay (Neutral Red uptake). This study has revealed an absence of PCO toxicity during exposure for 24 h and for concentrations ranging from 0.031 to 1‰ (w/v) on rat renal mesangial cells. We observed a lack of cytotoxicity response for the PCO mixture dissolved in medium. Quantitative assessments of the planar cell surface area (PCSA) were performed with an accurate automatized image analyser. The use of isolated cultured mesangial cells permits us to evaluate by quantitative morphometric analysis the contracture elicited either with CdCl₂ salts alone or by previous incubation with a non-lethal dose of PCO. When renal mesangial cells were exposed for 10 min to the PCO mixture, the Cd-mediated myocontracturant response of the mesangial cells was totally abolished. These results suggest that polyphenols could be effective against renal damages induced by cadmium. Received: 23 August 1999 / Accepted: 6 September 1999