Neuroprotective Potential of Cerium Oxide Nanoparticles for Focal Cerebral Ischemic Stroke

During the previous years, with the emerging of nanotechnology, the enormous capabilities of nanoparticles have drawn great attention from researchers in terms of their potentials in various aspects of pharmacology. Cerium oxide nanoparticles（nanoceria）, considered as one of the most widely used nanomaterials, due to its tempting catalytic antioxidant properties, show a promising potential in diverse disorders, such as cerebral ischemic stroke（CIS）, cancer, neurodegenerative and inflammatory diseases. Overwhelming generation of reactive oxygen species（ROS） and reactive nitrogen species（RNS） during cerebral ischemia and reperfusion periods is known to aggravate brain damage via sophisticated cellular and molecular mechanisms, and therefore exploration of the antioxidant capacities of nanoceria becomes a new approach in reducing cerebral ischemic injury. Furthermore, utilizing nanoceria as a drug carrier might display the propensity to overcome limitations or inefficacy of other conceivable neuroprotectants and exhibit synergistic effects. In this review, we emphasize on the principle features of nanoceria and current researches concerning nanoceria as a potential therapeutic agent or carrier in improving the prognosis of CIS.

An overview on recent in vivo biological application of cerium oxide nanoparticles

Cerium oxide nanoparticles(CNPs)possess a great potential as therapeutic agents due to their ability to self-regenerate by reversibly switching between two valences+3 and+4.This article reviews recent articles dealing with in vivo studies of CNPs towards Alzheimer’s disease,obesity,liver inflammation,cancer,sepsis,amyotrophic lateral sclerosis,acute kidney injury,radiation-induced tissue damage,hepatic ischemia reperfusion injury,retinal diseases and constipation.In vivo anti-cancer studies revealed the effectiveness of CNPs to reduce tumor growth and angiogenesis in melanoma,ovarian,breast and retinoblastoma cancer cell-induced mice,with their conjugation with folic acid,doxorubicin,CPM,or CXC receptor-4 antagonist ligand eliciting higher efficiency.After conjugation with triphenylphosphonium or magnetite nanoparticles,CNPs were shown to combat Alzheimer’s disease by reducing amyloid-β,glial fibrillary acidic protein,inflammatory and oxidative stress markers in mice.By improving muscle function and longevity,the citrate/EDTA-stabilized CNPs could ameliorate amyotrophic lateral sclerosis.Also,they could effectively reduce obesity in mice by scavenging ROS and reducing adipogenesis,triglyceride synthesis,GAPDH enzyme activity,leptin and insulin levels.In CCl4-induced rats,stress signaling pathways due to inflammatory cytokines,liver enzymes,oxidative and endoplasmic reticulum messengers could be attenuated by CNPs.Commercial CNPs showed protective effects on rats with hepatic ischemia reperfusion and peritonitis-induced hepatic/cardiac injuries by decreasing oxidative stress and hepatic/cardiac inflammation.The same CNPs could improve kidney function by diminishing renal superoxide,hyperglycemia and tubular damage in peritonitis-induced acute kidney injury in rats.Radiation-induced lung and testicular tissue damage could be alleviated in mice,with the former showing improvement in pulmonary distress and bronchoconstriction and the latter exhibiting restoration in spermatogenesis rate and spermatid/spermatocyte number.Through enhancement of gastrointestinal motility,the CNPs could alleviate constipation in both young and old rats.They could also protect rat from light-induced retinal damage by slowing down neurodegenerative process and microglial activation.

Cerium-based nanoparticles for cancer photodynamic therapy

Metal-and metal-oxide-based nanoparticles have been widely exploited in cancer photodynamic therapy(PDT).Among these materials,cerium-based nanoparticles have drawn extensive attention due to their superior biosafety and distinctive physicochemical properties,especially the reversible transition between the valence states of Ce(Ⅲ)and Ce(Ⅳ).In this review,the recent advances in the use of cerium-based nanoparticles as novel photosensitizers for cancer PDT are discussed,and the activation mechanisms for electron transfer to generate singlet oxygen are presented.In addition,the types of cerium-based nanoparticles used for PDT of cancer are summarized.Finally,the challenges and prospects of clinical translations of cerium-based nanoparticles are briefly addressed.

A new risk assessment method for evaluation of oxidative chemicals using catalase mutant mouse primary hepatocytes

We examined the possibility of developing a new risk assessment method for potentially hazardous chemicals by using mouse primary hepatocytes from acatalasemic mice (Csb) and the wild-type (Csa) as predictive model. Chemical-induced cytotoxicities, such as hydrogen peroxide and lawsone, a main hair dye ingredient of henna, were examined. We observed the differences in cell survival between the Csa and Csb in a dose-dependant manner after treatment with either hydrogen peroxide or lawsone, supporting the usefulness of this newly established method for hazard identification of oxidative chemicals in a risk assessment process. More chemicals will be tested to confirm the usefulness of this method for the preliminary screening of oxidative chemicals before animal experimentation.

In vitro and in vivo evaluation of cerium oxide nanoparticles in respiratory syncytial virus infection

Respiratory syncytial virus(RSV)is the most common cause of viral bronchiolitis among children worldwide,yet there is no vaccine for RSV disease.This study investigates the potential of cube and sphere-shaped cerium oxide nanoparticles(CNP)to modulate reactive oxygen(ROS)and nitrogen(RNS)species and immune cell phenotypes in the presence of RSV infection in vitro and in vivo.Cube and sphere-shaped CNP were synthesized by hydrothermal and ultrasonication methods,respectively.Physico-chemical characterization confirmed the shape of sphere and cube CNP and effect of various parameters on their particle size distribution and zeta potential.In vitro results revealed that sphere and cube CNP differentially modulated ROS and RNS levels in J774 macrophages.Specifically,cube CNP significantly reduced RSV-induced ROS levels without affecting RNS levels while sphere CNP increased RSV-induced RNS levels with minimal effect on ROS levels.Cube CNP drove an M1 phenotype in RSV-infected macrophages in vitro by increasing macrophage surface expression of CD80 and CD86 with a concomitant increase in TNFαand IL-12p70,while simultaneously decreasing M2 CD206 expression.Intranasal administration of sphere and cube-CNP were well-tolerated with no observed toxicity in BALB/c mice.Notably,cube CNP preferentially accumulated in murine alveolar macrophages and induced their activation,avoiding enhanced uptake and activation of other inflammatory cells such as neutrophils,which are associated with RSV-mediated inflammation.In conclusion,we report that sphere and cube CNP modulate macrophage polarization and innate cellular responses during RSV infection.

ROS Balance Autoregulating Core-Shell CeO_(2)@ZIF-8/Au Nanoplatform for Wound Repair

Reactive oxygen species(ROS)plays important roles in living organisms.While ROS is a double-edged sword,which can eliminate drug-resistant bacteria,but excessive levels can cause oxidative damage to cells.A core–shell nanozyme,Ce O_(2)@ZIF-8/Au,has been crafted,spontaneously activating both ROS generating and scavenging functions,achieving the multifaceted functions of eliminating bacteria,reducing inflammation,and promoting wound healing.The Au Nanoparticles(NPs)on the shell exhibit high-efficiency peroxidase-like activity,producing ROS to kill bacteria.Meanwhile,the encapsulation of Ce O_(2) core within ZIF-8 provides a seal for temporarily limiting the superoxide dismutase and catalase-like activities of Ce O_(2) nanoparticles.Subsequently,as the ZIF-8 structure decomposes in the acidic microenvironment,the Ce O_(2) core is gradually released,exerting its ROS scavenging activity to eliminate excess ROS produced by the Au NPs.These two functions automatically and continuously regulate the balance of ROS levels,ultimately achieving the function of killing bacteria,reducing inflammation,and promoting wound healing.Such innovative ROS spontaneous regulators hold immense potential for revolutionizing the field of antibacterial agents and therapies.

Regenerative cerium oxide nanozymes alleviate oxidative stress for efficient dry eye disease treatment

Dry eye disease(DED)is the most common eye disease in ophthalmic consultation except for refractive errors.Therefore,an exploration of valid and alternative therapeutic interventions is essential to feed the urgent medical need.It has been demonstrated that oxidative stress causes multiple adverse effects in the pathogenesis of DED,thence alleviating oxidative stress is an effective therapeutic strategy for the DED treatment.Herein,we developed a cerium oxide nanozyme combined with branched poly(ethylene imine)-graftpoly(ethylene glycol)(bPEI-g-PEG).Owing to its stable hydrophilic chains on the surface reducing the cytotoxicity and loads of amines groups that be combined with cerium ions through coordination bonds,the modified nanozymes(referred to as CNP@bPEI-g-PEG)are water soluble and highly biocompatible.Meanwhile,due to its excellent antioxidant activity,CNP@bPEI-g-PEG nanozymes can mimic the activity of superoxide dismutase and catalase to scavenge intracellular reactive oxygen species(ROS).Experimental studies firmly demonstrated that the modified nanozymes were auto-regenerative and more active in scavenging excessive ROS and alleviating oxidative stress by cerium-element valence state recycling,recovering the morphology of corneal,conjunctival epithelium and the number of goblet cells.The advanced combination may offer a superior therapeutic strategy to deal with oxidative stress for effective treatment of DED.

Ginsenosides from Stems and Leaves of Ginseng Prevent Ethanol-Induced Lipid Accumulation in Human L02 Hepatocytes

Objective： To investigate the effect of ginsenosides from stems and leaves of ginseng on ethanolinduced lipid deposition in human LO2 hepatocytes. Methods： LO2 cells were exposed to ethanol for 36 h and treated with or without ginsenosides. The viability of LO2 cells was evaluated by methylthiazolyldiphenyl- tetrazolium bromide assay and the triglyceride （TG） content was detected. Lipid droplets were determined by oil red O staining. Intracellular reactive oxygen species （ROS） production and the mitochondrial membrane potential were tested by flow cytometry. The ATP level was measured by reverse phase high performance liquid chromatography. The expression of cytochrome p450 2E1 （CYP2E1） and peroxisome proliferator- activated receptor （PPAR α） was detected by reverse transcriptase-polymerase chain reaction and Western blotting, respectively. Results： Ethanol exposure resulted in the increase of TG level, lipid accumulation and ROS generation, and the decrease of mitochondrial membrane potential and ATP production in the cells. However, ginsenosides significantly reduced TG content （9.69 ± 0.22 μg/mg protein vs. 4.93 ± 0.49 μg/mg protein, P〈0.01）, and ROS formation （7254.8± 385.7 vs. 5825.2± 375.9, P〈0.01）. Meanwhile, improvements in mitochondrial membrane potential （10655.33± 331.34 vs. 11129.52 ± 262.35, P〈0.05） and ATP level （1.20±0.18 nmol/mg protein vs. 2.53±0.25 nmol/mg protein, P〈0.01） were observed by treatment with ginsenosides. Furthermore, ginsenosides could down-regulate CYP2E1 expression （P〈0.01） and upregulate PPAR α expression （P〈0.01） in ethanol-treated cells. Conclusions： Ginsenosides could prevent ethanol-induced hepatocyte steatosis in vitro related to the inhibition of oxidative stress and the improvement of mitochondrial function. In addition, the modulation of CYP2E1 and PPAR α expression may also play an important role in the protective effect of ginsenosides against lipid accumulation.

纳米氧化铈抗氧化保护心肌细胞的研究进展

纳米氧化铈(CeNPs)是一种很强的自由基清除剂。研究表明,CeNPs可预防炎症导致的氧化应激,也可调节免疫反应缓解炎症。炎症期间,不同的免疫反应具有明显不同的能量需求。过量的活性氧会造成氧化应激,而线粒体或其他细胞内来源产生的活性氧在心肌细胞缺血再灌注损伤的发病机制中起关键作用,CeNPs因其具有极好的氧缓冲能力及生物可降解性,目前在抗氧化研究中受到极大关注。现综述国内外CeNPs抵抗氧化应激、保护心肌细胞的具体机制,可能为CeNPs在临床心血管疾病的治疗中提供新的理论依据。

竹叶花椒提取物抑制大鼠肝细胞BRL 3A自噬而诱导ROS累积

目的研究竹叶花椒甲醇提取物(ZADCM)对BRL 3A细胞自噬水平与活性氧(ROS)生成量的影响。方法体外培养BRL 3A细胞,将其与ZADCM(70μg·mL^(-1))处理3、6、12、24 h或不同浓度的ZADCM(30、50、70μg·mL^(-1))孵育24 h,干预给药用3-甲基腺嘌呤(10 mmol·L^(-1))、二甲双胍(2.5 mmol·L^(-1))处理;采用CCK-8法检测BRL 3A细胞存活率,流式细胞术检测BRL 3A细胞内ROS生成量,免疫荧光法观察自噬标志性蛋白LC3B的荧光强度,Western blotting检测p-mTOR、mTOR、p-ULK1、ULK1、Beclin-1和LC3B蛋白的表达。结果不同浓度ZADCM处理24 h后,与正常对照组比较,免疫荧光结果显示LC3B荧光强度降低;ZADCM(70μg·mL^(-1))处理12或24 h后,Western blotting结果显示,LC3B和Beclin-1蛋白表达水平均降低(P<0.05或P<0.01),p-mTOR^(2448)/mTOR、p-ULK1^(757)/ULK1均显著升高(P<0.05)。激光共聚焦结果显示ROS灶点增加,且流式细胞术结果显示,药物处理组的ROS水平均明显升高(P<0.05或P<0.01);采用3-甲基腺嘌呤或二甲双胍干预后,与药物处理组比较,细胞内ROS升高或降低,自噬相关蛋白表达降低或升高,ZADCM组BRL 3A细胞存活率降低或升高。结论ZADCM可能通过激活BRL 3A细胞内mTOR/ULK1信号通路,抑制细胞自噬,并伴随ROS累积,引起细胞活力下降。

CeO_(2)纳米颗粒调控活性氧稳态和一氧化氮水平提高水稻耐旱能力

干旱是影响水稻产量和品质的常见限制因素之一。氧化铈纳米颗粒在提高作物抗逆中已有广泛报道。然而,氧化铈纳米颗粒是否能提高水稻耐旱能力以及相应的机制目前仍不清除。本研究旨在分析氧化铈纳米颗粒是否可以通过影响活性氧稳态和一氧化氮水平提高水稻抗旱。结果表明,与无纳米材料对照相比,氧化铈纳米颗粒显著增加了干旱胁迫下的水稻幼苗的鲜重(19%,P<0.05)。同时,干旱胁迫下,氧化铈纳米颗粒处理组水稻叶片的活性氧水平显著低于无纳米材料对照组(82%,P<0.05),而其叶片一氧化氮荧光信号则显著高于对照组(46%,P<0.05)。此外,与无纳米材料对照相比,干旱胁迫下,氧化铈纳米颗粒处理组水稻叶片细胞表现出更好的膜完整性,其死细胞数下降70%(P<0.05)。本研究从活性氧和一氧化氮信号分子的角度初步探索了氧化铈纳米颗粒提高水稻抗旱性的机制,不仅进一步丰富了纳米材料与逆境条件下的作物相互作用的理论基础,而且有利于纳米农业的可持续发展。

利用类器官培养构建小鼠肝脏衰老模型

目的利用类器官培养构建体外快速诱导的小鼠肝脏衰老模型。方法通过两步灌注法获取小鼠肝细胞并对其进行类器官培养。通过形态学、qPCR和免疫荧光对类器官进行初步鉴定,通过检测其对LDL的摄取能力判断肝脏类器官的功能。用油酸(OA)处理肝脏类器官,检测其生长情况、衰老相关分泌表型、LDL的摄取能力和肝细胞活性氧(ROS)水平,分析肝脏衰老模型构建是否成功。进一步使用N-乙酰半胱氨酸(NAC)处理肝细胞,检测以上表型和功能的变化,利用此模型探究ROS对衰老的影响。结果两步灌注法获取到大量有活性的原代小鼠肝细胞,通过在基质胶中3D培养可获得具有自我复制能力的肝脏类器官,qPCR显示其表达肝脏标志基因,免疫荧光结果显示其高表达白蛋白(ALB),并且肝脏类器官具有对LDL正常的摄取功能。用油酸处理后,肝脏类器官生长减慢,衰老相关分泌表型基因表达上调(P<0.001),对LDL的摄取能力降低(P<0.001),ROS明显上升(P<0.001)。以上表型在使用NAC处理后均得以缓解(P<0.01或P<0.001)。结论油酸处理可在体外成功构建小鼠肝脏的衰老模型,加入NAC后可清除ROS,减缓衰老的发生。

稀土元素铈对细胞内活性氧的影响

运用显微荧光术研究了Ce3+ 对肝细胞和V79细胞中活性氧 (ROS)的影响。结果表明 ,低浓度的Ce3 + 能显著降低细胞内ROS浓度 ,而高浓度的Ce3+ 能显著提高细胞内ROS的浓度。结果提示 ,低浓度的Ce3 + 可能减少脂质过氧化损伤或DNA氧化损伤 ,高浓度的Ce3 + 可能增加脂质过氧化损伤或DNA氧化损伤。

辛硫磷对大鼠肝细胞凋亡的影响

通过给大鼠肝细胞培养液中加入辛硫磷（染毒终浓度分别为3、10、30、100和300／zmol／L）染毒，于12、24h后用流式细胞仪分别测定细胞凋亡率、细胞死亡率和细胞内活性氧（ROS）水平，并在扫描电镜和荧光显微镜下观察细胞凋亡情况，研究了辛硫磷对原代培养大鼠肝细胞凋亡的影响。结果显示，辛硫磷具有明显的细胞毒性，在3～100μmol／L范围内随着染毒剂量的增大和染毒时间的延长，细胞死亡率、凋亡率和ROS水平显著升高，且发生了明显的细胞凋亡的形态学变化；但300μmol／L辛硫磷培养24h，肝细胞凋亡率和ROS水平下降，死亡率升高。表明辛硫磷对肝细胞有直接的毒性作用，并通过产生ROS诱导了肝细胞凋亡。

天麻素对乙醇诱导肝细胞株L02细胞损伤的影响

目的:探讨天麻素对乙醇诱导肝细胞株L02损伤的影响。方法:将人肝细胞株L02培养,加入不同浓度的乙醇,采用MTT比色法确定乙醇作用的浓度。用流式细胞仪测定细胞活性氧簇(ROS)及线粒体膜电位的改变;采用反相高效液相色谱(RP-HPLC)分析法检测细胞ATP含量。结果:乙醇(25 mL/L)作用36 h可损伤肝细胞,细胞内ROS的水平明显增加;而细胞线粒体膜电位及肝细胞中ATP的含量则显著降低(P<0.01)。天麻素具有减轻细胞损伤的作用,并可降低损伤的肝细胞内ROS的含量,增加细胞线粒体膜电位和ATP的水平。结论:天麻素可抑制乙醇诱导的肝细胞损伤及脂质过氧化反应,改善线粒体功能,增加能量合成,发挥保护肝细胞的作用。

阿魏酸钠对转化生长因子β_1抑制肝细胞增殖作用的影响

目的 探讨转化生长因子 β1(TGFβ1)抑制肝细胞生长过程中 ,阿魏酸钠 (sodiumferulic,SF)的干预作用。方法 以培养的正常人肝细胞株 (L0 2细胞 )为对照 ,5 μg·L-1TGFβ1处理的细胞为模型组 ,MTT比色法及3 H TdR参入法分别检测TGFβ1及SF对L0 2细胞生长和DNA合成的影响 ;以流式细胞计数仪分析TGFβ1和SF对L0 2细胞周期各时相变化的影响 ;采用化学荧光探针DCFH DA ,经流式细胞计数仪检测TGFβ1致细胞内活性氧自由基 (ROS)生成情况及不同浓度的SF的干预作用。结果 5 μg·L-1TGFβ1处理L0 2细胞 2 4h ,细胞存活率下降为对照组的 6 7 93% (P <0 0 1vs对照组 ) ,细胞DNA合成抑制率为 37 5 6 % ,2 5 0μmol·L-1SF可以使L0 2细胞存活率升高 19 2 8% (P <0 0 1vs模型组 ) ,DNA合成增加 17 71% (P <0 0 5vs模型组 ) ;SF促进L0 2细胞周期由G0 /G1期向S期和G2 /M期过渡 ,12 5 μmol·L-1和 2 5 0 μmol·L-1SF使L0 2细胞周期S期的比例分别增加 11 4 5 %和 17 92 % (P <0 0 1vs模型组 ) ;5 μg·L-1TGFβ1使L0 2细胞内ROS产生量升高为对照组的1 90倍 ,6 2 5 μmol·L-1～ 2 5 0 μmol·L-1SF分别降低TGFβ1的诱导作用 14 5 %～ 2 7 5 %。结论 阿魏酸钠对抗由TGFβ1引起的肝细胞生长抑制作用 。

活性氧及能量代谢障碍在体外培养肝细胞脂肪变性中的作用

目的:探讨细胞活性氧(ROS)及线粒体能量代谢障碍在乙醇和小牛血清诱导的体外培养肝细胞脂肪变性中的作用。方法:将人肝细胞株L02进行细胞培养,加入不同浓度的乙醇,采用MTT法确定乙醇作用的最佳浓度;用2%乙醇和50%小牛血清(A+CS)诱导L02细胞,以油红O染色观察细胞内脂滴形成状况,并检测细胞TG的含量;用流式细胞仪(FCM)测定细胞活性氧及线粒体膜电位的改变;采用反相高效液相色谱分析法测定细胞ATP含量。结果:2%乙醇和50%小牛血清作用36h,肝细胞内有典型的脂滴形成,与对照组相比,细胞内TG含量及ROS水平明显增加;而细胞线粒体膜电位及肝细胞ATP的含量则显著降低(P<0.01)。结论:在乙醇和小牛血清诱导肝细胞脂肪变过程中,细胞ROS的增加及线粒体能量代谢障碍可能发挥了重要的作用。

依非韦伦的肝细胞毒性作用及对蛋白质表达谱的影响

目的探讨依非韦伦对肝细胞的毒性作用及对蛋白质表达谱的影响。方法人肝癌细胞系Huh7中分别加入依非韦伦1.25,2.5,5和10 mg.L-1,培养5 h后采用原位比色法测定细胞内活性氧类(ROS)的含量;依非韦伦2.5 mg.L-1与细胞作用5 h后,用膜联蛋白-Ⅴ/碘化丙啶细胞凋亡检测试剂盒染色。用流式细胞仪测定细胞凋亡;依非韦伦2.5 mg.L-1处理细胞5 h,获得全细胞蛋白质进行二维凝胶电泳,采用ImageMaster软件分析差异蛋白质点,应用纳升级液相色谱串联电喷雾离子阱质谱进行差异蛋白质鉴定。结果随着依非韦伦浓度的增加,细胞内ROS的含量逐步升高(r=0.9740,P<0.05)。依非韦伦2.5 mg.L-1与细胞作用5 h后,与正常对照组比较,细胞凋亡百分率无显著变化,但有7种蛋白质表达量显著降低,其中线粒体热激蛋白75和抗氧化蛋白1的表达量分别降低了76.7%和85.5%;抗胰蛋白酶及其S突变体、细胞角蛋白9、剪接体相关蛋白和磷酸丙糖异构酶的表达被完全抑制。结论依非韦伦对Huh7细胞具有明显的细胞毒性,可能通过调节热激蛋白75和抗氧化蛋白1等的表达影响线粒体的功能,最终导致肝毒性的发生。

西维来司钠对大鼠重症急性胰腺炎后急性肝损伤的保护作用

目的:探讨西维来司钠对大鼠重症急性胰腺炎(SAP)后急性肝损伤的治疗价值。方法:SD大鼠54只随机分为3组,A组为对照组,仅开腹,轻翻动胰腺,B组采用经十二指肠乳头逆行胆胰管注射3.5%牛磺胆酸钠的方法制备大鼠SAP模型,C组为西维来司钠药物治疗组,在制备SAP大鼠模型后微量泵持续静脉滴注西维来司钠;各组又分为3h、6h、12h3个亚组,每时间点6只。检测血浆白介素-6(IL-6)、中性粒细胞弹性蛋白酶(NE)、淀粉酶(AMY)及肝组织匀浆中超氧化物歧化酶(SOD)、丙二醛(MDA)的水平并观察肝、胰病理变化。结果(:1)B组IL-6、NE、AMY、MDA较A组明显升高(P<0.05),SOD明显降低(P<0.05),镜下可见胰腺水肿、炎细胞浸润、坏死,肝脏肝窦充血、细胞浊肿及坏死,且损伤程度随时限延长而加重。(2)C组较B组血浆IL-6、NE、AMY(12h)及肝组织匀浆中MDA水平下降(P<0.05),SOD升高(P<0.05),胰、肝病理损害程度减轻。结论:西维来司钠通过抑制NE的活性及在肝组织中的表达,抑制SAP急性期炎症反应及有效提高机体对氧自由基的清除能力,减轻SAP致肝损伤的程度。

肝细胞生长因子在肾脏缺血-再灌注损伤中的表达改变及意义

目的通过对肾脏缺血再灌注时肾组织内肝细胞生长因子(HGF)mRNA及肾组织内丙二醛(MDA)和超氧化物歧化酶(SOD)活性的检测,揭示肾脏缺血再灌注过程中HGFmRNA表达变化及与SOD、MDA变化的相关性。方法雄性SD大鼠40只,切除右肾,1周后随机分为假手术组及实验组,每组20只,建立缺血再灌注损伤的模型。测定各组大鼠肾功能,对比2组间肾脏HGFmRNA、MDA及SOD的含量。结果实验组大鼠肾功能明显下降,表明肾脏缺血再灌注模型制作成功。与假手术组相比,缺血再灌注组肾组织SOD活性明显降低;MDA含量增高,二者相比差异具有统计学意义(P<0.05);肾脏HGFmRNA表达,再灌注组较假手术组增高,差异有统计学意义(P<0.01)。缺血再灌注过程中,肾脏HGFmRNA变化与SOD变化呈负相关,与MDA呈正相关。结论自由基的损伤性刺激可能是再灌注损伤过程中引起肾脏HGFmRNA表达上调的原因之一。