南沙参多糖对四氯化碳损伤原代培养大鼠肝细胞保护作用的研究

目的:探讨南沙参多糖(RAPS)对四氯化碳(CCl4)损伤原代培养大鼠肝细胞的保护作用及其机制。方法:通过原位灌流法分离大鼠肝细胞,培养36h后加入RAPS,同时造成CCl4损伤,分别于损伤24h和48h时检测培养液中丙二醛(MDA)的含量、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)的活性,48h后用MTT法测定肝细胞存活率。结果:RAPS对CCl4引起的ALT、AST活力的升高有抑制作用,同时抑制MDA的产生及肝细胞损伤造成的SOD活性及GSH-PX活性的降低。而且能明显改善肝细胞存活率。结论:RAPS能有效抑制CCl4造成的原代培养大鼠肝细胞损伤,机制可能与其抗氧化作用有关。     

玉郎伞多糖对过氧化氢诱导大鼠原代肝细胞损伤的保护作用

目的研究玉郎伞多糖(YLS)对H2O2诱导大鼠原代肝细胞损伤的保护作用及其机理。方法采用IV型胶原酶灌流法分离大鼠肝细胞进行原代培养,用H2O2体外诱导肝细胞损伤,检测培养上清液中AST和ALT水平,测定肝细胞中MDA和GSH含量,MTT法检测细胞存活和增殖活性。结果YLS(0.125~1 mg/ml)可明显降低或恢复由H2O2升高的培养上清液中AST和ALT水平及肝细胞中MDA含量,还可提高H2O2降低的肝细胞存活率和GSH含量。结论提示YLS对大鼠原代培养肝细胞损伤有直接保护作用,该作用可能与其抗氧化作用有关。     

PM_(2.5)对大鼠肝、脾、肾组织的氧化损伤效应

目的探讨PM2.5对大鼠肝、脾、肾组织抗氧化酶活力和脂质过氧化(LPO)水平的影响。方法选取32只雄性Wistar大鼠,随机分为4组,分别用0、1.5、7.5、37.5mg/kg的PM2.5经气管注入染毒后24h处死大鼠,测定肝、脾、肾组织超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)活力,谷胱甘肽(GSH)和硫代巴比妥酸反应物(TBARS)含量。结果PM2.5染毒组大鼠肝、肾组织内SOD、CAT、GSH-Px活力和SOD/TBARS比值均较对照组降低(P<0.05,P<0.01),具有剂量-效应关系。各染毒组TBARS/GSH-Px比值较对照组显著升高(P<0.01,P<0.001)。染毒组脾、肾组织GSH含量较对照组显著下降(P<0.05,P<0.01),而染毒组肝组织GSH含量则出现先升高后降低的非线性变化特征(P<0.01,P<0.05)。染毒组肝组织LPO水平出现剂量-效应性升高(P<0.05),染毒组脾组织各种抗氧化酶活力、LPO水平和TBARS/GSH-Px比值均未见显著变化。结论PM2.5可引起大鼠肝、肾组织的氧化损伤。     

麦粒灸对阿霉素所致心肌病大鼠抗氧化应激作用的影响

目的:探讨麦粒灸对阿霉素(DOX)所致心肌病大鼠抗氧化应激作用的影响。方法:SD大鼠随机分为空白组、模型组和麦粒灸组,每组20只。模型组及麦粒灸组腹腔注射DOX复制心肌病模型。麦粒灸组在给药的同时取“关元”“巨阙”穴进行麦粒灸治疗,每日1次,共治疗4周。检测大鼠心率(HR)、左心室收缩压(LVSP)、左心室舒张压(LVDP)、等容收缩期左心室内压最大上升速率(+dp/dtmax)、等容舒张期左心室内压最大下降速率(-dp/dtmax)、左室内压变化时间(t-dp/dtmax)评价心功能;光镜下观察心肌病理组织形态学改变;酶联免疫法测定大鼠血清乳酸脱氢酶(LDH)、磷酸肌酸激酶(CK)及心肌组织中超氧化物歧化酶(SOD)活性及心肌组织中丙二醛(MDA)、血清心肌肌钙蛋白Ⅰ(cTnⅠ)的含量。结果:与空白组比较,模型组HR、LVSP、+dp/dtmax、-dp/dtmax降低,LVDP和t-dp/dtmax升高,差异有统计学意义(P0.05);与模型组比较,麦粒灸组HR、LVSP、+dp/dtmax、-dp/dtmax升高,LVDP和t-dp/dtmax降低,差异有统计学意义(P0.05)。与空白组比较,模型组光镜下呈心肌病样改变,细胞肿胀充血、排列紊乱,白细胞浸润明显;模型组、麦粒灸组大鼠血清LDH、CK活性与cTnⅠ表达水平及心肌MDA含量显著升高(P0.01),心肌SOD活性显著下降(P0.01);与模型组比较,光镜下麦粒灸组心肌细胞轻微肿胀、出血,大鼠血清LDH、CK活性与cTnⅠ表达水平及心肌MDA含量显著降低(P0.01),心肌SOD活性显著升高(P0.01)。结论:麦粒灸可显著减轻DOX引起的心肌细胞损伤,其机制可能与麦粒灸提高SOD活性、降低MDA含量来抑制心肌细胞氧化应激损伤,从而实现对DOX心肌病大鼠的心肌保护作用有关。     

Proteomic study of the effects of complex environmental stresses in the livers of goldfish (<Emphasis Type="Italic">Carassius auratus</Emphasis>) that inhabit Gaobeidian Lake in Beijing,China

Recent advances in proteomics have provided an excellent opportunity to understand biological adaptation under complex environmental stress at the protein level. Gaobeidian Lake, located in Beijing, China, is characterized by complex environmental stresses by serving as both the effluent of a wastewater treatment plant and a coolant of a nearby thermal power plant. Liver is the primary organ of energy metabolism and xenobiotic detoxification. To further our understanding of how organisms that live in Gaobeidian Lake acclimatize themselves to these complex environmental stresses, hepatic protein expression patterns were examined in goldfish Carassius auratus that inhabit the lake. Huairou Reservoir, a drinking water source, was used as a reference site. Twenty four protein spots, which were differently expressed in the two sites, were further digested with trypsin and analyzed by matrix-assisted laser desorption/ionization (MALDI) tandem time of flight mass spectrometry (TOF/TOF). The expression of several energy metabolism and oxidative stress proteins, such as glutathione peroxidase (GPx), ferritin H3, and liver basic fatty acid-binding protein (Lb-FABP) were found to be altered in this stressful environment. In addition to the up-regulation of GPx translation, both the mRNA levels and enzymatic activity of GPx protein were elevated in goldfish living in Gaobeidian Lake. The expression of both peroxisome proliferator activated receptor (PPAR), one of the most important metabolism and stress regulation genes as well as cytochrome P450 1A1 (CYP1A1), a detoxification gene, was also detected by real-time PCR at the two sites. Increased expression levels of both PPAR-beta and CYP1A1 (P < 0.1) were observed in Gaobeidian Lake. Our study provides an integrative view of the expression levels of hepatic proteins and genes in goldfish under complex environmental stress that live in Gaobeidian Lake. Our results showed that anthropogenic environmental stresses in Gaobeidian Lake activated the regulation gene of lipid metabolism PPAR, elevated the lipid metabolism levels, and activated the anti-oxidative adaptation mechanism of organisms in the lake.     

血红素加氧酶-1表达对大鼠呼吸机相关性肺损伤的作用及机制研究

目的 观察呼吸机相关性肺损伤(VILI)模型大鼠肺组织中血红素加氧酶-1(HO-1)表达的变化,探讨HO-1诱导剂血晶素拮抗VILI的作用机制.方法 56只雄性SD大鼠按照随机数字表法分成对照组(C组),VILI模型组(M组),诱导剂血晶素1、2、3、4组(H1、 H2、H3、H4组,制模前24 h分别腹腔注射血晶素40、80、120、160 μmol/kg)和抑制剂Z组[制模前24 h腹腔注射锌原卟啉(ZnPP)10 μmol/kg].除C组外各组机械通气4 h后处死大鼠,收集支气管肺泡灌洗液(BALF),测定总蛋白、肿瘤坏死因子-α(TNF-α)和白细胞介素-10(IL-10)含量;取肺组织,测定肺湿/干重(W/D)比值、乳酸脱氢酶(LDH)、超氧化物歧化酶(SOD)和丙二醛(MDA)水平及HO-1蛋白表达;光镜下行肺组织病理观察.结果 与C组相比,M组大鼠肺病理损伤严重,BALF中总蛋白、TNF-α、IL-10,肺组织W/D比值、MDA、LDH及HO-1蛋白表达均明显增加, VILI模型复制成功.与M组比较,随着血晶素剂量的增加,H1、H2、H3组总蛋白(g/L)显著下降(0.74±0.06、0.73±0.07、0.70±0.07比0.84±0.08,均P<0.01);W/D比值下降(4.93±0.27、4.91±0.24、4.87±0.23比5.53±0.48,均P<0.01);SOD活性(U/mg)显著升高(85±9、82±15、93±11比55±12,均P<0.01);MDA含量(nmol/mg)显著降低(15±3、15±3、13±2比18±4,P<0.05或P<0.01);IL-10含量(pg/L)逐渐升高(0.42±0.06、0.46±0.06、0.47±0.05比0.36±0.07),TNF-α含量(pg/L)逐渐降低(0.18±0.07、0.14±0.03、0.10±0.07比0.23±0.06),但只有H2、H3组差异有统计学意义(均P<0.01);LDH活性(U/g)降低(11 353±1 317、11 516±1 613、9 631±1 520比12 361±1 841),但仅H3组差异有统计学意义(P<0.01);HO-1蛋白表达[吸光度(A)值]逐渐增强(0.164±0.010、0.190±0.149、0.205±0.018比0.122±0.016,均P<0.01);肺病理损伤逐渐减轻.而随着剂量进一步增加,H4组肺组织损伤较H1、H2、H3组加重.给予HO-1抑制剂ZnPP后HO-1的保护作用消失.结论 血晶素诱导HO-1适度表达可以减轻VILI,其适度表达的最佳剂量为120 μmol/kg,其机制可能通过抗炎和抗氧化应激发挥对肺组织的保护作用.     

PM2.5对大鼠肝、脾、肾组织的氧化损伤效应

目的探讨PMU对大鼠肝、脾、肾组织抗氧化酶活力和脂质过氧化（LPO）水平的影响。方法选取32只雄性Wistar大鼠,随机分为4组,分别用0、1．5、7．5、37．5mg／kg的PMu经气管注入染毒后24h处死大鼠,测定肝、脾、肾组织超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GSH—Px）活力,谷胱甘肽（GSH）和硫代巴比妥酸反应物（TBARS）含量。结果PM”染毒组大鼠肝、肾组织内SOD、CAT、GSH—Px活力和SOD／TBARS比值均较对照组降低（P〈0．05,P〈0．01）,具有剂量一效应关系。各染毒组TBARS／GSH—Px比值较对照组显著升高（P〈0．01,P〈0．001）。染毒组脾、肾组织GSH含量较对照组显著下降（P〈0．05,P〈0．01）,而染毒组肝组织GSH含量则出现先升高后降低的非线性变化特征（P〈0．01,P〈0．05）。染毒组肝组织LPO水平出现剂量-效应性升高（P〈0．05）,染毒组脾组织各种抗氧化酶活力、LPO水平和TBARS／GSH—Px比值均未见显著变化。结论PM2.5可引起大鼠肝、肾组织的氧化损伤。     

牛磺酸对哺乳动物大脑发育及抗缺氧缺血性脑损伤的作用

牛磺酸是存在于哺乳动物大脑中类似γ-氨基丁酸的抑制性氨基酸,可与甘氨酸受体结合激活皮质纹状体通路,发挥着平衡大脑兴奋性和抑制性过程的重要作用.它的浓度在哺乳动物大脑发育过程中持续升高至断奶期,到成年后达到稳定水平.牛磺酸具有强大的抗氧化应激、抗炎和抗凋亡作用,并且可以改善缺氧缺血性脑损伤,促进神经细胞增殖分化,影响胎儿脑发育.动物实验表明补充牛磺酸可促进新生儿脑发育,有保护或减轻脑缺氧缺血性和氧化应激脑损伤的作用.但对于人类能否补充牛磺酸来促进脑发育保护脑损伤,以及在何时补充、补充的剂量和途径的研究资料并不充分,有待于进一步深入研究.     

The inhibitory activities of Urtica fissa to BPH

In the present study, the BPH inhibitory activities of Urtica fissa were systematically investigated. Firstly, inhibitory activities of 5α reductase of the alcoholic extracts from different parts (root, stem, leaf, flower and fruit) were evaluated. The results indicated that the root possessed the most significant action. Subsequently, U. fissa root (UFR) was subjected to further pharmacological evaluation using the benign prostate hyperplasia (BPH) model rats induced by testosterone propionate. The results revealed that UFR could significantly decrease the prostate index, alter the hyperplasia tissue morphology, suppress the prostatic growth factors of VEGF, EGF, bFGF and KGF, decrease the inflammation factor levels of TNF-α, IL-1βand IL-6, improve the activities of GSH-Px, CAT and SOD and decrease the MDA level in the prostate of the model rats. Moreover, UFR also significantly suppressed the hormone levels of testosterone and dihydrotestosterone. These results indicated that the possible BPH inhibitory mechanisms of UFR were growth factor suppression, hormone level modulation, anti-inflammation, and anti-oxidative stress.     

碘缺乏与碘过量对小鼠血液氧应激状态的影响

目的 观察昆明小鼠摄入不同剂量碘酸钾(KIO3)对血液抗氧化能力的影响.方法 将200只昆明小鼠随机分为5个剂量组:低碘组(LI)、适碘组(NI)、5倍高碘组(5HI)、10倍高碘组(10HI)、50倍高碘组(50HI),每组再分为雌雄两个组.LI组饲以低碘地区的粮食制成的饲料(平均碘含量为20～40 μg/kg),其它4组饲以正常鼠饲料(平均碘含量为300 μg/kg),LI组、NI组饮用去离子水,各高碘组分别饮用含不同浓度(2 023.6、4 553.2、24 789.6 μg/L)碘酸钾的去离子水,每只小鼠每日的总摄碘量依次为0.1～0.2、1.5、7.5、15、75μg.喂养3和6个月后,检测抗凝全血的谷胱甘肽过氧化酶(GPx)活力、红细胞超氧化物歧化酶(SOD)活力以及血浆丙二醛(MDA)含量.结果 LI组的GPx活力在3和6个月时较NI组降低,LI组的MDA含量在6个月时较NI组升高,50HI组的MDA含量在6个月时较NI组降低,差异有统计学意义(P＜0.05).雌性组GPx活力、SOD活力和MDA含量与同剂量的雄性组比较,差异无统计学意义.结论 碘缺乏会导致大鼠血液抗氧化能力降低,但长期摄入较高剂量的KIO3并未对大鼠血液产生过氧化损伤,而且雌性和雄性间无差异.