钴-原卟啉诱导大鼠血红素加氧酶-1适度过表达的研究

目的研究钴-原卟啉(CoPP)诱导大鼠血红素加氧酶-1(HO-1)的适度过表达,并观察其抗肝缺血/再灌注损伤(IRI)的作用。方法建立大鼠肝脏IRI模型,按体重给予不同诱导剂量的CoPP(5、2.5mg/kg及2.5mg/kg体重2次),关用锌原卟啉(ZnPP)来抑制HO-1的活性。观察血浆谷草转氨酶(AST)、乳酸脱氢酶(LDH)、肝组织丙二醛(MDA)的变化,肝组织光镜和电镜下的改变,肝组织HO-1蛋白表达的Western印迹。结果CoPP诱导组中均有明显的HO-1蛋白表达;与缺血/再灌注(IR)组比较,CoPP诱导组动物血浆AST、LDH活性以及肝MDA含量明显降低,肝组织损伤减轻。3个剂量组中以2.5mg/kg体重诱导2次效果最佳。ZnPP的加入阻断了CoPP诱导组的这些保护作用。结论CoPP诱导HO-1适度过表达的诱导剂量为2.5mg/kg体重2次,在这一诱导剂量下HO-1过表达对肝IRI具有重要的保护作用。     

HO-1高表达对脂肪干细胞在低氧无血清条件下的保护作用及机制

 目的:探讨诱导内源性血红素氧合酶-1（HO-1）表达对脂肪干细胞（ADSCs）在低氧无血清条件下的保护作用及其可能的分子机制。方法: 分离培养SD大鼠脂肪干细胞进行低氧无血清处理,DAPI染色检测细胞凋亡率;Western blotting 法分析HO-1、NLRP3 、凋亡相关斑点样蛋白 (ASC)和cleaved caspase-1的蛋白表达;ELISA 法测定培养上清液中白细胞介素-1β (IL-1β) 的水平;采用 DCFH-DA 荧光探针检测细胞内活性氧 (ROS) 的水平。结果: 钴原卟啉诱导ADSCs HO-1蛋白呈剂量依赖性表达,以20 μmol/L最为显著;诱导内源性HO-1的表达明显抑制ADSCs在低氧无血清条件下的细胞凋亡率和NLRP3、ASC、cleaved caspase-1的蛋白表达,并减少细胞内ROS和上清液IL-1β的水平;而这种保护效应可被同时给予的HO-1抑制剂锌原卟啉所逆转。结论: 诱导内源性HO-1的表达可能通过抑制NLRP3炎症小体的激活以及减少IL-1β的分泌,对低氧无血清条件下ADSCs发挥保护作用。     

类叶升麻苷通过诱导血红素加氧酶-1的表达抑制MPP+诱导的PC12细胞损伤

目的 探讨类叶升麻苷(AS)是否在PC12细胞中诱导血红素加氧酶-1(HO-1)的表达进而抑制1-甲基-4-苯基吡啶(MPP+)诱导的神经毒性损伤.方法 类叶升麻苷(1、20和30 μmol/L)处理PC12细胞12 h,利用反转录PCR(RT-PCR)检测HO-1 mRNA表达、Western blot方法和免疫荧光方法检测HO-1蛋白的表达.1mmol/L MPP+单独或与AS处理细胞,或HO-1抑制剂锌原卟啉(ZnPP)预处理细胞1h,MTT法检测细胞活力.结果 与正常对照组相比,AS可在PC12细胞中诱导HO-1 mRNA和蛋白的表达,AS诱导的HO-1表达主要集中在胞浆内.HO-1抑制剂ZnPP减弱AS对MPP+诱导损伤的抑制作用.结论 AS可在PC12细胞中诱导HO-1的表达,可能参与AS对MPP+诱导损伤的抑制作用.     

HO-1在造影剂所致肾小管上皮细胞损伤中的作用

目的:探讨血红素加氧酶-1(Heme oxygenase-1,HO-1)在造影剂所致肾小管上皮细胞损伤中的作用.方法:体外培养的HK-2细胞,分为正常对照组、甘露醇对照组、造影剂损伤组、钴原卟啉(CoPP)处理组、锌原卟啉(ZnPP)处理组.比色法测定细胞培养上清液乳酸脱氢酶(LDH)水平,四甲基偶氮唑(methyl ...     

大鼠肢体缺血—再灌注所致肾损伤及其机制探讨

目的探讨肢体缺血-再灌注后脑内诱导型血红素氧合酶(HO-1)表达的变化及意义.方法SD大鼠随机分为正常(N),假手术(S),后肢单纯缺血(I),后肢缺血-再灌注(I-R)2h、6h、12h、18h、24h,后肢I-R18h+ZnPP(HO-1活性抑制剂锌原卟啉)各组.夹闭双侧股动脉根部4h,开放2h-24h,制备I及I-R各组模型,I-R18h+ZnPP组,再灌注6h、12h时经股静脉注射ZnPP(每次5μmol/kg).反转录-多聚酶链反应(RT-PCR)检测脑组织HO-1mRNA表达的变化,以HO-1与β-actin(内参对照物)mRNA逆转录扩增产物电泳谱带的积分灰度值的比值,作为HO-1mRNA的半定量结果;免疫组化染色法观察HO-1蛋白在脑内的生成与分布;应用ZnPP抑制HO-1活性后,观察脑组织的病理学变化,比色法测定脑组织MDA含量及SOD活性的变化.结果(1)N组脑组织HO-1mRNA的相对表达量为0.053±0.004,S组为0.064±0.007,I组为0.142±0.049,均较N组显著升高,P＜0.05;肢体I-R后脑组织HO-1mRNA表达上调,I-R12h至峰值,此后回降,I-R2h、6h、12h、18h和24h各组的相对表达量依次为0.155±0.028、0.609±0.034、0.680±0.036、0.481±0.060和0.526±0.052,I-R6h、12h、18h和24h各组较N、S及I组显著升高,P＜0.01.(2)N、S及I组大脑皮质、海马等区域可见少量散在分布的HO-1阳性神经元.I-R6h组大脑皮质可见大量弥散分布的HO-1阳性锥体细胞及少量阳性胶质细胞,海马锥体层细胞呈阳性反应.I-R12h组大脑皮层及海马区出现大量HO-1阳性胶质细胞.(3)I-R18h±ZnPP组脑组织病变较I-R18h组加重,大脑皮质及海马部分神经元明显水肿,部分神经元核固缩,细胞周围出现水肿裂隙.(4)I-R18h+ZnPP组与I-R18h组相比,SOD活性下降,MDA含量增高(P＜0.05).结论肢体I-R后脑内HO-1表达上调,神经元表达HO-1时相早,但维持时间短,胶质细胞表达HO-1较迟,但维持时间长,胶质细胞是脑组织表达HO-1的主要细胞基础.抑制HO-1活性后脑损伤加重,脑内过氧化反应增强,表明HO-1具有抗氧化保护效应.     

生殖支原体脂质相关膜蛋白诱导胎盘滋养层细胞表达血红素氧合酶1从而负调控细胞因子分泌

目的观察生殖支原体脂质相关膜蛋白(LAMP)能否诱导胎盘滋养层细胞表达血红素氧合酶1(HO-1),从而影响细胞因子的产生。方法体外培养胎盘滋养层细胞,用0.5~5μg/m L LAMP作用4~12 h。实时定量PCR和Western blot法分别检测HO-1 mRNA和蛋白的表达以及核因子相关因子2(Nrf2)的核转位;2',7'-二氯二氢荧光黄二乙酸酯(H2DCFDA)检测活性氧(ROS)产生;采用N-乙酰半胱氨酸(NAC)或Nrf2 siRNA处理滋养层细胞,观察其对HO-1表达的影响。采用HO-1的激动剂钴原卟啉(Co PP),抑制剂锌原卟啉(Zn PP)或HO-1 siRNA处理细胞,ELISA检测处理前后LAMP对诱导肿瘤坏死因子α(TNF-α)和白细胞介素1β(IL-1β)分泌的影响。结果 LAMP能诱导滋养层细胞HO-1 mRNA和蛋白表达,并能诱导其产生ROS以及促进Nrf2核转位。ROS抑制剂NAC预处理后,可明显降低HO-1的表达水平以及细胞核内Nrf2含量。同时,Nrf2siRNA转染后,HO-1表达显著减少。采用Zn PP处理滋养层细胞,或RNA干扰HO-1表达后,可促进LAMP诱导滋养层细胞分泌TNF-α和IL-1β,而Co PP处理能进一步降低TNF-α和IL-1β水平。结论 LAMP能通过ROS/Nrf2诱导滋养层细胞表达HO-1,从而抑制细胞因子的过度分泌。     

大鼠肢体缺血-再灌注后脑组织HO-1表达的变化

目的:探讨肢体缺血-再灌注后脑内诱导型血红素氧合酶(HO-1)表达的变化及意义.方法: SD大鼠随机分为正常(N),假手术(S),后肢单纯缺血(I),后肢缺血-再灌注(I-R) 2 h、6 h 、12 h、18 h、24 h,后肢I-R18 h+ZnPP(HO-1活性抑制剂锌原卟啉)各组.夹闭双侧股动脉根部4 h,开放2 h-24 h,制备I及I-R各组模型,I-R18 h+ZnPP组,再灌注6 h、12 h时经股静脉注射Z nPP (每次5 μmol/kg).反转录-多聚酶链反应(RT-PCR)检测脑组织HO-1 mRNA表达的变化,以H O-1与β-actin(内参对照物)mRNA逆转录扩增产物电泳谱带的积分灰度值的比值,作为HO-1mRNA的半定量结果;免疫组化染色法观察HO-1蛋白在脑内的生成与分布;应用ZnPP抑制HO-1活性后 ,观察脑组织的病理学变化,比色法测定脑组织MDA含量及SOD活性的变化.结果: (1)N组脑组织HO-1mRNA的相对表达量为0.053±0.004,S组为0.064±0.007,I 组为0.142±0.049,均较N组显著升高,P＜0.05;肢体I-R后脑组织HO-1mRNA表达上调,I-R12 h至峰值,此后回降,I-R 2 h、6 h、12 h、18 h和24 h各组的相对表达量依次为0.155±0.028、0.609±0.034、0. 680±0.036、0.481±0.060和0.526±0.052,I-R6 h、12 h、18 h和24 h各组较N、S 及I组显著升高,P＜0.01.(2)N、S及I组大脑皮质、海马等区域可见少量散在分布的HO-1阳性神经元. I-R6 h组大脑皮质可见大量弥散分布的HO-1阳性锥体细胞及少量阳性胶质细胞,海马锥体层细胞呈阳性反应.I-R12 h组大脑皮层及海马区出现大量HO-1阳性胶质细胞.(3)I-R18h±Zn PP组脑组织病变较I-R18h组加重,大脑皮质及海马部分神经元明显水肿,部分神经元核固缩 , 细胞周围出现水肿裂隙.(4)I-R18h+ZnPP组与I-R18h组相比,SOD活性下降,MDA含量增高( P＜0.05).结论:肢体I-R后脑内HO-1表达上调,神经元表达HO- 1时相早,但维持时间短,胶质细胞表达HO-1较迟,但维持时间长,胶质细胞是脑组织表达HO-1的主要细胞基础 .抑制HO-1活性后脑损伤加重,脑内过氧化反应增强,表明HO-1具有抗氧化保护效应.     

大鼠肢体缺血—再灌注后肾组织量HO—1表达的变化

目的探讨大鼠肢体缺血-再灌注后肾内诱导型血红素氧合酶(HO-1)表达的变化及意义.方法SD大鼠随机分为正常(N),假手术(S),后肢单纯缺血(I),后肢缺血-再灌注(I-R)2h、6h、12h、18h、24h,后肢I-R18h+ZnPP(锌原卟啉)各组.夹闭双侧股动脉根部4h,开放2h-24h,制备I及I-R各组模型,I-R18h+ZnPP组,再灌注6h、12h时经股静脉注射ZnPP(每次5μmol/kg).反转录-多聚酶链反应(RT-PCR)检测肾HO-1mRNA表达的变化,以HO-1与β-actin(内参对照物)mRNA逆转录扩增产物电泳谱带的积分灰度值的比值,作为HO-1mRNA的半定量结果;免疫组化染色法观察HO-1蛋白在肾内的生成与分布;应用ZnPP抑制HO-1活性后,光镜观察肝组织的病理学变化,比色法测定肾组织MDA含量及SOD活性的变化.结果(1)N组肾组织HO-1mRNA未检出,S组肾组织HO-1mRNA的相对表达量为0.333±0.037,I组为0.549±0.035,与S组相比有显著差异,P＜0.01;肢体I-R后肾组织HO-1mRNA表达进一步上调,I-R18h至峰值,此后回降,I-R2h、6h、12h、18h和24h各组肾组织HO-1mRNA表达量依次为1.017±0.088、1.322±0.052、1.356±0.073、1.765±0.092和1.443±0.023,与S、I组相比均有显著差异,P＜0.01.(2)S、I及I-R6h组髓袢小管上皮细胞呈HO-1免疫阳性,3组相比染色依次加深,I-R12h组肾小管各段上皮细胞均呈阳性,肾小球等血管内皮呈弱阳性.(3)I-R18h+ZnPP组肾组织病变较I-R18h组加重,肾小管上皮细胞严重水肿,肾小球毛细血管内淤积大量红细胞.(4)I-R18+ZnPP组与I-R18h组相比,SOD活性下降,MDA含量增高,P＜0.01.结论肢体I-R后肾内HO-1表达上调,表达HO-1的细胞主要是肾小管上皮细胞,HO-1出现的部位及范围与损伤的部位及范围有相关性.抑制HO-1活性使肾损伤加重,肾内过氧化反应增强,表明HO-1具有抗氧化保护效应.     

大鼠肢体缺血—再灌注后肝组织量HO—1表达的变化

目的探讨大鼠肢体缺血-再灌注后肝内诱导型血红素氧合酶(HO-1)表达的变化及意义.方法SD大鼠随机分为正常(N),假手术(S),后肢单纯缺血(1),后肢缺血-再灌注(I-R)2h、6h、12h、18h、24h,后肢I-R18h+ZnPP(HO-1活性抑制剂锌原卟啉)各组.夹闭双侧股动脉根部4h,开放2-24h,制备I及I-R各组模型,I-R18h+ZnPP组,再灌注6h、12h时经股静脉注射ZnPP(每次5μmol/kg).反转录-多聚酶链反应(RT-PCR)检测肝组织HO-1mRNA表达的变化,以HO-1与β-actin(内参对照物)mRNA逆转录扩增产物电泳谱带的积分灰度值的比值,作为HO-1mRNA的半定量结果;免疫组化染色法观察HO-1蛋白在肝内的生成与分布;应用ZnPP抑制HO-1活性后,光镜观察肝组织的病理学变化,比色法测定肝组织MDA含量及SOD活性的变化.结果(1)N组肝组织HO-1mRNA的相对表达量为0.104±0.006,S组为0.163±0.011,I组为1.285±0.083,均较N组显著升高,P＜0.01;肢体I-R后肝组织HO-1mRNA表达上调,I-R12h至峰值,此后回降,I-R2h、6h、12h、18h和24h各组的表达量依次为1.833±0.048、1.847±0.048、3.781±0.132、1.875±0.077和0.742±0.036,均较N、S组显著升高(P＜0.01),I-R2h、6h、12h和18h各组与I组相比有显著差异,P＜0.01.(2)N、S和I组可见散在分布的HO-1阳性肝细胞,I-R组大部分肝细胞呈HO-1阳性.(3)I-R18h+ZnPP组肝组织病变较I-R18h组加重,肝血管明显收缩,肝细胞严重水肿.(4)I-R18h+ZnPP组与I-R18h组相比,SOD活性下降,MDA含量增高(P＜0.01).结论肢体I-R后肝内HO-1表达上调,表达HO-1的主要是肝细胞,抑制HO-1活性使肝损伤加重,肝内脂质过氧化反应增强,表明HO-1的诱生具有抗氧化保护效应.     

甲基莲心碱对脑缺血再灌注脑损伤的调节作用

目的探讨甲基莲心碱(Neferine,Nef)对缺血再灌注脑损伤大鼠脑保护作用及其机制.方法线栓法建立大鼠脑缺血再灌注损伤(CI/R)模型.造模后对大鼠神经功能进行评分;HE检测病理损伤;检测血清MDA、SOD和LDH含量;TUNEL检测脑细胞凋亡;RT-PCR检测Caspase-3、-9 mRNA表达;免疫组化检测脑组织ICAM-1表达;ELISA检测IL-6、IL-18和IL-1β的含量;蛋白印迹检测TLR4、NF-κB P65(核)和MIP-2表达.结果甲基莲心碱能有效改善脑缺血再灌注损伤大鼠的神经功能(P<0.01),减少造模诱导的脑组织病理损伤;减少MDA和LDH含量(P<0.01),增加SOD活性(P<0.01);减少脑组织细胞凋亡率(P<0.01),下调凋亡相关蛋白Caspase-3、-9 mRNA表达水平(P<0.01);降低促炎因子(ICAM-1)、炎性因子(IL-6,IL-18,IL-1β)和炎性蛋白(TLR4,NF-κB P65,MIP-2)在脑组织中的表达水平(P<0.01).结论甲基莲心碱能对脑缺血再灌注损伤大鼠脑组织起保护作用,其机制与减少凋亡及抑制炎性反应有关.     

锌原卟啉测定对孕妇缺铁性贫血的临床诊断意义

为探讨锌原卟啉（ZPP）作为缺铁性贫血诊断指标的意义及孕妇早、中、晚期缺铁发病率，本文对139例孕早期，280例孕中期以及208例孕晚期共627例孕妇ZPP含量进行了测定分析，另对17例孕早期，182例孕中期以及152例孕晚期共351例孕妇的（血红蛋白）Hb、（红细胞）RBC、（红细胞压积）HCT、（红细胞平均容积）MCV、（红细胞平均血红蛋白）MCH及（红细胞平均血红蛋白浓度）MCHC共6项指标进行了测定，结果表明：孕晚期ZPP含量显著高于孕早、中期组（P＜0．01），而孕早、中期间无显著性差异。孕晚期组的Hb、RBC、MCH及MCHC与早孕期组相比显著降低（P＜0．01），HCT各组间无显著性差异（P＞0．05），ZPP含量与Hb呈显著负相关，与RBC呈正相关，综上结果看出孕晚期ZPP含量增高明显，提示ZPP的检测可作为监测孕妇缺铁性贫血一项指标。     

Homozygous variegate porphyria A severe skin disease of Infancy

A boy exhibited severe bullous skin disease a few days after birth, followed by increased fragility of the exposed skin in spring and summer. Examination at 2 1/2 years of age led to characteristic biochemical findings: increased excretion of fecal porphyrins (coproporphyrin 121 to 131 and protoporphyrin 467 to 576 nmol/g dry weight), and increased erythrocyte protoporphyrin concentration (3643 to 4840 nmol/I). Lymphocyte protoporphyrinogen oxidase activity was very low in the patient (0.4 nmol/mg protein/h) and half-normal (2.7 and 2.3 nmol/mg protein/h) in the parents, suggesting that the patient had homozygous variegate porphyria. Severe skin symptoms and a high concentration of red cell protoporphyrin concentration in an infant should prompt suspicion of homozygous acute hepatic porphyria.     

Sideroblastic anemia: molecular analysis of the ALAS2 gene in a series of 29 probands and functional studies of 10 missense mutations

X-linked Sideroblastic Anemia (XLSA) is the most common genetic form of sideroblastic anemia, a heterogeneous group of disorders characterized by iron deposits in the mitochondria of erythroid precursors. XLSA is due to mutations in the erythroid-specific 5-aminolevulinate synthase (ALAS2) gene. Thirteen different ALAS2 mutations were identified in 16 out of 29 probands with sideroblastic anemia. One third of the patients were females with a highly skewed X-chromosome inactivation. The identification of seven novel mutations in the ALAS2 gene, six missense mutations, and one deletion in the proximal promoter extends the allelic heterogeneity of XSLA. Most of the missense mutations were predicted to be deleterious, and 10 of them, without any published functional characterization, were expressed in Escherichia coli. ALAS2 activities were assayed in vitro. Five missense mutations resulted in decreased enzymatic activity under standard conditions, and two other mutated proteins had decreased activity when assayed in the absence of exogenous pyridoxal phosphate and increased thermosensitivity. Although most amino acid substitutions result in a clearly decreased enzymatic activity in vitro, a few mutations have a more subtle effect on the protein that is only revealed by in vitro tests under specific conditions.     

Effects of glycine on cell growth and pigment biosynthesis in Rhodobacter azotoformans

The effect of exogenous glycine (a precursor for the biosynthesis of bacteriochlorophyll) on the cell growth and photopigment accumulation was investigated in phototrophic growing Rhodobacter azotoformans 134K20. The growth rate and the biomass of strain 134K20 were significantly inhibited by glycine addition when ammonium sulfate or glutamate were used as nitrogen sources and acetate or succinate as carbon sources. A characteristic absorption maximum at approximately 423 nm was present in the absorption spectra of glutamate cultures while it was absent by the addition of high-concentration glycine of 15 mM. The component account for the 423 nm peak was eventually identified as magnesium protoporphyrin IX monomethyl ester, a precursor of bacteriochlorophyll a (BChl a). Comparative analysis of pigment composition revealed that the amount of BChl a precursors was significantly decreased by the addition of 15-mM glycine while the BChl a accumulation was increased. Moreover, glycine changed the carotenoid compositions and stimulated the accumulation of spheroidene. The A₈₅₀/A₈₇₅ in the growth-inhibited cultures was increased, indicating an increased level of the light-harvesting complex 2 compared to the reaction center. The exogenous glycine possibly played an important regulation role in photosynthesis of purple bacteria.     

Infectious bronchitis virus and brown shell colour: Australian strains of infectious bronchitis virus affect brown eggshell colour in commercial laying hens differently

The aim of the current study was to assess any effect of wild and vaccine Australian infectious bronchitis virus (IBV) strains on shell colour in brown-shelled eggs. In Experiment 1, eggs were collected from day 1 to day 13 post-inoculation (p.i.) from unvaccinated laying hens challenged with IBV wild strains T and N1/88 and from a negative control group of hens. In Experiment 2, eggs were collected from 2 to 22 days p.i. from unvaccinated and vaccinated laying hens challenged with either a wild or a vaccine strain of IBV. In Experiment 1, there was a significant effect (P?相似文献   

A physiological role for protoporphyrin IX photodynamic action in the rat Harderian gland?

Aims: The lipid‐secreting exocrine Harderian gland contains a large amount of porphyrins (mainly protoporphyrin IX, PPIX) in the glandular cells, the physiological significance of which is rather poorly understood. Methods: In the present study, the possibility of using Fura‐2 to measure intracellular calcium ([Ca²⁺]_c) changes in these cells was assessed. Results: It was found that when Fura‐2‐loaded cells were excited by light at 340/380 nm, [Ca²⁺]_c increased spontaneously, indicating a photodynamic action powered by light at 340/380 nm. In contrast, with the visible spectrum calcium probe Fluo‐3 (λ_ex = 475 nm), carbachol at 10 μm induced [Ca²⁺]_c increase; [Ca²⁺]_c did not change without carbachol stimulation. Brief illumination with light at 340/380 nm induced a large [Ca²⁺]_c increase in Fluo‐3‐loaded cells. Photodynamic stimulation of [Ca²⁺]_c increase was confirmed with an exogenous photosensitizer sulphonated aluminium phthalocyanine (SALPC) and visible light (>580 nm). The wavelength‐dependence of the [Ca²⁺]_c increase correlates well with the excitation spectrum of the isolated Harderian glandular cells. Conclusion: These data suggest that PPIX present in rat Harderian glandular cells plays the role of a photosensitizer which upon activation by UVA and blue components of daylight and subsequent singlet oxygen generation, triggers [Ca²⁺]_c increase and secretory response. The PPIX photodynamic action may also play a potential role in photic entrainment of the central circadian clock.     

Liver pathology and hepatocarcinogenesis in a long-term mouse model of erythropoietic protoporphyria

Erythropoietic protoporphyria (EPP) is an inherited disease of haem synthesis caused by a mutation in one of the alleles of the enzyme ferrochelatase. This mutation leads to partial deficiency of the enzyme, resulting in increased concentrations of protoporphyrin (PP) in blood, liver, and faeces. Five to ten per cent of patients with EPP develop severe liver disease characterized by the presence of PP deposits. This study used histochemistry and immunohistochemistry to investigate the histopathological features present in the livers of 44 mice with a heterozygous or homozygous point mutation in the ferrochelatase gene (fch/+ and fch/fch mice, respectively). Some fch/+ mouse livers showed mixed steatosis and large cell dysplasia. The livers of fch/fch mice showed periportal or septal fibrosis accompanied by an atypical ductular reaction. These findings suggest that the obstruction and damage of a proportion of large and small bile ducts by PP deposits cause an accumulation of PP in the parenchyma, which leads to damage and loss of hepatocytes due to the toxic effects of PP. The classical stages of hepatocarcinogenesis were observed and hepatic progenitor cells appear to be involved in this process. PP acts as the promoting agent and is probably also the initiating agent.     

Insulin-like growth factor-I stimulates erythropoiesis when administered enterally

Background: Insulin-like growth factors I and II (IGF-I and IGF-II) are potent growth factors involved in development. IGF-I stimulates proliferation of erythropoietic progenitors and parenteral IGF-I administration stimulates in vivo erythropoiesis in animals. IGF-I and IGF-II are both present in mammalian milks and when milk-borne, are resistant to neonatal gastrointestinal degradation. Whether milk-borne IGF-I or IGF-II regulates neonatal erythropoiesis in not known. We hypothesized that physiological doses of enteral IGFs stimulate erythropoiesis in suckling rats.

Methods: Eight day-old Sprague Dawley rats were artificially fed for 4 days with rat milk substitute (RMS) or RMS supplemented with physiological levels of IGF-I or IGF-II. Rats fed IGF-I and IGF-II were compared to control RMS. Blood and marrow were collected; measures of red cell mass, measures of erythropoietic stimulus, and indices of iron status were measured.

Results: Rats fed IGF-I had higher hemoglobin (Hb) levels (100 ± 10 g/l), compared to those fed RMS (94 ± 9) or IGF-II (91 ± 6), p < 0.001. After IGF-I supplementation, red blood cell counts (RBC) (p < 0.04) and hematocrits (p < 0.002) were also higher. Plasma erythropoietin (Epo) levels, reticulocytes, plasma iron and erythrocyte iron incorporation were similar.

Conclusion: Intact enteral IGF-I reaches distal erythropoietic tissue resulting in greater red cell mass, but not by increasing plasma Epo levels or by altering cellular iron transport.