不同剂量葡萄籽原花青素对砷致雄性小鼠肝脏毒性拮抗作用研究

目的观察不同剂量葡萄籽提取物原花青素对三氧化二砷(As2O3)所致雄性小鼠肝脏毒性干预效果,研究其抗氧化损伤作用机制及其干预效果的差异。方法按体重分层将50只雄性昆明种小鼠随机分为5组:对照组(生理盐水0.9%)、As2O3组(4 mg/kg·bw)、和As2O3(4 mg/kg·bw)+GSPE低(100 mg/kg·bw)、中(200 mg/kg·bw)、高(400 mg/kg·bw)剂量组,每组10只,连续灌胃5周;称量小鼠体重、肝重,并计算其肝脏系数;测定肝脏组织的天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽(GSH)、T-AOC等指标,采用单因素方差分析对比组间差异。结果 As2O3组体重、GSH含量、T-AOC水平均低于对照组,肝重、肝脏系数、ALT、AST活力、MDA含量均高于对照组(P均<0.05);As2O3+GSPE(200、400)mg/(kg·bw)剂量组体重均高于As2O3组(P均<0.05);As2O3+GSPE(100、200、400)mg/(kg·bw)剂量组肝重、肝脏系数、ALT、AST活力、MDA含量均低于As2O3组(P均<0.05);GSH含量、T-AOC水平均高于As2O3组(P均<0.05)。As2O3+GSPE低剂量组小鼠体重比As2O3+GSPE中剂量组低(P<0.05);As2O3+GSPE低、中、高剂量组GSH含量(137.17±34.70)μmol/g prot、(198.02±41.28)μmol/g prot、(272.06±35.85)μmol/g prot、T-AOC水平(5.33±0.76)U/mL、(7.07±0.83)U/mL、(11.54±1.86)U/mL依次增高(P<0.05)。结论 GSPE可能通过抗氧化损伤作用拮抗As2O3致雄性小鼠的肝脏毒性,高剂量GSPE干预效果较好。     

原花青素对氟致雄性小鼠生殖系统氧化损伤的拮抗作用

为研究原花青素(GSP)对氟致雄性小鼠的生殖系统氧化损伤的拮抗效应,将40只健康性成熟SPF级昆明雄性小鼠随机分为对照(生理盐水)组、NaF(20 mg/kg)组、GSP(200 mg/kg)组及NaF(20mg/kg)+GSP(200mg/kg)组,每组10只.采用灌胃方式进行染毒,连续染毒35 d.检测睾丸组织匀浆中超氧化物歧化酶(SOD)活力和丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH)、8-羟基脱氧鸟嘌呤(8-OHdG)含量及总抗氧化能力(T-AOC)水平.结果显示,与对照组相比,NaF组小鼠睾丸组织匀浆中MDA和8-OHdG含量均增高,GSH含量、T-AOC水平和SOD活力均降低,差异有统计学意义(P＜0.05);而GSP组小鼠睾丸组织匀浆中SOD活力和T-AOC水平均增高,差异均有统计学意义(P＜0.05).与NaF组相比,GSP+NaF组小鼠睾丸组织匀浆中MDA和8-OHdG含量均降低,GSH含量、T-AOC水平和SOD活力均升高,差异有统计学意义(P＜0.05).经析因分析,NaF与GSP两种因素同时作用时对小鼠睾丸组织匀浆中MDA和GSH含量存在交互作用(P＜0.05),表现为拮抗作用;而对小鼠睾丸组织中T-AOC水平、SOD活力及8-OHdG含量无交互作用(P＞0.05).提示GSP对氟化钠导致的雄性小鼠生殖系统氧化损伤具有一定的拮抗作用.     

叶黄素对砷致小鼠肝脏毒性的预防保护作用

目的观察提前给予小鼠叶黄素干预对砷肝脏毒性的预防效果。方法将84只SPF级昆明种小鼠,雌雄各半,随机分为35 d空白组、70 d空白组、35 d单纯叶黄素组、70 d单纯叶黄素组、砷染毒组、35 d叶黄素拮抗组和70 d叶黄素预防组,按叶黄素40 mg/kg,As2O35 mg/kg剂量灌胃给药。测定血清中谷氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)活性,肝脏匀浆丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性、还原型谷胱甘肽(GSH)含量、总抗氧化能力(T-AOC)及一氧化氮(NO)含量,采用单因素方差分析对比组间差异。结果砷染毒组AST和ALT活性、MDA含量显著高于70 d空白组,SOD活性、GSH及NO含量、T-AOC水平显著低于70 d空白组(P<0.05);70 d叶黄素预防组AST及ALT活性、MDA含量低于35 d叶黄素拮抗组(P<0.05),SOD活性、NO及GSH含量、T-AOC水平均高于35 d叶黄素拮抗组(P<0.05)。结论提前给予叶黄素干预可以提高小鼠肝脏组织抗氧化损伤能力,从而拮抗砷的肝脏毒性作用。     

六价铬污染地下水和重铬酸钾染毒对小鼠肝脏和血糖的影响及维生素C的干预作用

目的了解六价铬[C(rⅥ)]污染地区地下水对小鼠肝脏、血糖的影响和维生素C(VitC)的干预作用。方法将80只健康6～8周龄清洁级雄性昆明小鼠随机分为8组,分别为对照(蒸馏水)组、铬污染的井水[采自某被污染的地下水,Cr(Ⅵ)含量为12.35 mg/L]组和34.91[C(rⅥ)含量为12.35 mg/L]、349.1、698.2、1 396.4 mg/L重铬酸钾单独染毒组以及VitC(100 mg/ml)+698.2、1396.4 mg/L重铬酸钾联合作用组,每组10只。采用经口灌胃方式进行染毒,重铬酸钾和井水组的染毒容量为25 ml/kg;VitC的染毒容量为5 ml/kg,0.5 h后再进行重铬酸钾染毒。连续染毒30 d。染毒结束后,测定血清天门冬氨酸氨基转移酶(AST)、谷丙氨酸氨基转移酶(ALT)活力和血糖(Glu)含量及肝脏超氧化物歧化酶(SOD)活力和谷胱甘肽(GSH)、丙二醛(MDA)含量。结果与对照组比较,井水组和不同浓度重铬酸钾单独染毒组小鼠血清AST、ALT活力和肝脏MDA含量均较高,肝脏SOD活力、GSH含量和血清Glu含量较低,差异有统计学意义(P<0.05);而经Vit C预处理各组小鼠血清AST、ALT活力和Glu含量及肝脏SOD活力和GSH、MDA含量无显著变化;且随着重铬酸钾染毒浓度的升高,小鼠血清AST、ALT活力及肝脏MDA含量呈上升趋势,肝脏SOD活力和GSH含量呈下降趋势。与相同浓度重铬酸钾单独染毒组比较,经VitC预处理各组小鼠血清AST、ALT活力和肝脏MDA含量均较低,血清Glu含量及肝脏SOD活力和GSH含量均较高,差异有统计学意义(P<0.05)。与34.91 mg/L重铬酸钾单独染毒组比较,井水组小鼠血清AST、ALT活力和肝脏MDA含量均较高,血清Glu含量及肝脏SOD活力和GSH含量均较低,差异有统计学意义(P<0.05)。结论 C(rⅥ)污染地区地下水可引起小鼠肝脏的损伤,且可能存在其他重金属污染;而Vit C对于重铬酸钾所致肝损伤有一定的拮抗作用。     

金属硫蛋白对镍铬联合染毒小鼠肝脏损伤的拮抗作用

目的研究硫酸镍+重铬酸钾联合染毒对小鼠肝脏损伤的影响及金属硫蛋白(MT)的拮抗作用。方法将50只健康SPF级昆明小鼠按体重随机分为5组,分别为溶剂对照组(生理盐水)、镍铬(1.0 mg/kg硫酸镍+0.5 mg/kg重铬酸钾)联合染毒组和低、中、高剂量MT保护(1.0 mg/kg硫酸镍+0.5 mg/kg重铬酸+5.0、10.0、20.0 mg/kg MT)组,每组10只,雌雄各半。采取灌胃方式进行染毒,染毒容量为10 ml/kg,每天1次,连续染毒21 d。检测小鼠丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、γ-谷氨酰转肽酶(GGT)活力及肝组织超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活力和丙二醛(MDA)、谷胱甘肽(GSH)含量。结果与溶剂对照组比较,镍铬联合染毒组小鼠血清AST、ALT、GGT的活力均增高,差异均有统计学意义(P0.05)。各剂量MT保护组小鼠血清AST、ALT、GGT的活力均低于镍铬联合染毒组,差异均有统计学意义(P0.05);且随着MT染毒剂量的升高,MT保护组小鼠血清AST、ALT、GGT的活性均呈下降趋势。与溶剂对照组比较,镍铬联合染毒组小鼠肝组织SOD、GSH-Px活力和GSH含量均下降,而MDA含量升高,差异均有统计学意义(P0.05)。与镍铬联合染毒组比较,各剂量MT保护组小鼠肝组织SOD、GSH-Px活力和GSH含量均升高,而MDA含量均降低,差异均有统计学意义(P0.05),且随着MT染毒剂量的升高,MT保护组小鼠肝组织SOD、GSH-Px活力和GSH含量均呈上升趋势,而MDA含量呈下降趋势。结论 MT对镍铬联合染毒所致小鼠肝脏损伤有较好的拮抗作用,其作用机制可能与MT抗氧化作用有关。     

二氯甲烷对小鼠肝功能影响的研究

目的探讨二氯甲烷(DCM)染毒对小鼠血清中肝功能及肝组织病理的影响。方法将昆明种雄性小鼠随机分为高、中、低剂量染毒组(染毒剂量分别为12 900、6 400、1 300mg/m3)和对照组(0mg/m3),每组6只。将小鼠成笼放入动式染毒室内,每天染毒2h,连续染毒30d后,检测血清中丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、碱性磷酸酶(ALP)、丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽(GSH)、总抗氧化能力(T-AOC)水平;取小鼠肝脏作石蜡切片,HE染色观察肝脏组织病理学变化。结果与对照组比较,各染毒组ALT、AST、ALP水平均有升高,差异均有统计学意义(P0.05);与对照组比较,各染毒组SOD、MDA含量均有升高(P0.05),GSH含量、T-AOC水平随染毒剂量的增加呈下降趋势(P0.05);组织病理切片显示小鼠肝脏出现炎症反应。结论 DCM吸入染毒对小鼠的肝脏功能有一定的影响,并出现炎症性病理变化。     

纳米二氧化钛经口暴露对小鼠肝脏的影响

目的 探讨纳米二氧化钛(TiO2 NPs)经口暴露后对小鼠肝脏的影响。方法 60只健康雄性ICR小鼠随机分为对照组、TiO2 NPs (10、50、100) mg/kg·BW染毒组,连续灌胃30 d后,颈椎脱臼处死小鼠,计算小鼠肝脏系数,观察小鼠肝脏组织病理学切片,测定肝组织匀浆中丙氨酸氨基转移酶(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)、总抗氧化能力(T - AOC)活力以及丙二醛(MDA)含量。结果 与对照组相比,各染毒组小鼠肝脏系数差异无统计学意义(P＞0.05);病理学切片观察各染毒组肝脏组织均可见不同程度肝组织损伤;随着TiO2 NPs染毒剂量的增加,ALT、AST活力以及MDA含量在50、100 mg/kg·BW组升高,SOD活性在100 mg/kg·BW组降低,GSH - PX活性在50、100 mg/kg·BW组降低,T - AOC水平在10、50、100 mg/kg·BW组均降低,差异均具有统计学意义(P＜0.05)。结论 经口暴露TiO2 NPs,可使小鼠肝脏发生氧化应激反应,造成肝脏氧化损伤,并最终导致小鼠肝脏组织结构及功能破坏,具有一定的肝脏毒性作用。     

维生素E对二甲基甲酰胺致小鼠急性肝损伤的拮抗作用

目的 探讨维生素E( Vitamin E,VE)对二甲基甲酰胺(N,N-dimethylformamide,DMF)致急性肝损伤的拮抗作用.方法 将50只健康SPF级雄性昆明小鼠随机分为5组,分别为正常对照组、VE( 10 mg/kg)对照组、DMF中毒模型组及低(5 mg/kg)、高(10 mg/kg)剂量VE保护组,每组10只.VE对照组和低、高剂量VE保护组采用灌胃方式染毒VE溶液,正常对照组和DMF中毒模型组分别染毒等体积玉米油,每天1次,连续5d;最后1次染毒VE后0.5 h,DMF中毒模型组及各剂量VE保护组一次性灌胃染毒2g/kg的DMF溶液,同时,正常对照组和VE对照组给等体积蒸馏水.检测小鼠血清丙氨酸氨基转氨酶(ALT)、天冬氨酸氨基转氨酶(AST)和黄嘌呤氧化酶(XOD)活力,肝脏匀浆中谷胱甘肽(GSH)和脂质过氧化产物丙二醛(MDA)的含量.结果 与DMF中毒模型组比较,VE保护组小鼠血清ALT、AST 、XOD活力显著降低(P＜0.05),肝脏GSH含量明显升高(P＜0.05),MDA含量显著下降(P＜0.05).结论 VE对DMF引起的小鼠肝损伤具有拮抗作用.     

三氧化二砷染毒小鼠肝脏中砷甲基化水平与肝脏氧化应激的关系

目的探讨三氧化二砷(As2O3)染毒小鼠肝脏组织中砷甲基化水平的变化及其与肝脏氧化应激关系,为揭示砷甲基化水平在砷毒性机制中的作用提供依据。方法将40只昆明种小鼠随机分为对照组(0.9%生理盐水)、As2O3低中高剂量组(1.0、2.0和4.0 mg/kg)组,连续灌胃5周;采用高效液相色谱与原子荧光联用技术(HPLC-HGAFS)测定肝脏组织中三价无机砷(As3+)、五价无机砷(As5+)、一甲基胂(MMA)、二甲基胂(DMA)含量及构成比(%),计算砷一甲基化指数(PMI)、二甲基化指数(SMI);利用试剂盒测定丙二醛(MDA)、谷胱甘肽(GSH)、超氧化物歧化酶(SOD)、总抗氧化能力(T-AOC)。结果随着As2O3剂量增加,小鼠肝脏组织中各形态砷代谢产物含量增加(P0.001),砷甲基化水平(i As%、MMA%、DMA%、PMI、SMI)提高(P0.001);小鼠肝脏MDA显著高于对照组(P0.001),GSH、SOD、T-AOC显著低于对照组(P0.001);1 mg/kg染毒剂量时,PMI与T-AOC呈负相关(P0.05),SMI与GSH、SOD呈负相关(P0.05);在2 mg/kg染毒剂量时,PMI、SMI与MDA呈正相关(P0.05)而与GSH、SOD呈负相关(P0.05);在4 mg/kg染毒剂量时,PMI与MDA呈正相关(P0.05),PMI、SMI与GSH、SOD呈负相关(P0.05)。结论随着砷染毒剂量的增加,小鼠肝脏组织中各种形态砷含量增多,砷甲基化水平提高,进而导致小鼠肝脏氧化损伤严重。     

糖尿病小鼠模型的组织氧化应激研究

[目的]探讨糖尿病小鼠模型组织氧化应激. [方法]给雄性昆明种小鼠喂养常规饮食一周后随机分成两组,其中一组经小剂量链脲佐菌素(STZ)注射后诱导成糖尿病小鼠,糖尿病组饲喂高脂饮食,4周后测量两组小鼠末期肝、肾、心、肺组织中脂质过氧化物丙二醛(MDA),谷胱甘肽(GSH),抗氧化酶(SOD,GPx,CAT)以及一氧化氮(NO),一氧化氮合酶(NOS)、脏器系数. [结果]试验结束时,糖尿病组小鼠一般情况较差,与正常组比较,体重显著降低(P＜0.01),肝、肾、肺脏器指数显著升高(P＜0.01);糖尿病组肝脏组织中MDA含量、GPx活性(P＜0.01)显著高子正常组.SOD、CAT、 NOS活性、GSH含量显著低于正常组(P＜0.01).糖尿病组小鼠肾脏组织中,GPx、SOD活性、MDA、NO含量显著高于正常组(P＜0.01);NOS、CAT活性、GSH含量显著低于正常组(P＜0.01).糖尿病组小鼠心脏组织中GPx活性、MDA含量显著高于正常组(P＜0.01);SOD活性、GSH含量显著低于正常组(P＜0.01).糖尿病组小鼠肺组织中SOD、GPx活性显著高于正常组(P＜0.01);CAT活性、NO、GSH含量显著低于正常组(P＜0.05).[结论]本研究表明糖尿病小鼠组织存在氧化应激.     

Calcium intake in the elderly: validation of a dietary questionnaire

Epidemiological studies of calcium and osteoporosis have been hampered by the lack of a suitable tool for assessing calcium intake. This report describes a new frequency and amount questionnaire for measuring present and past calcium intake in the elderly. The validity of the questionnaire was tested against two commonly used standards of dietary assessment, five-day duplicate diets and seven-day weighed dietary inventories. The resulting correlation coefficients were, respectively, r = 0.76 and r = 0.69, while that for repeatability was r = 0.84. Furthermore, the questionnaire categorized subjects into thirds of the distribution of intake with almost no gross misclassification. It is suggested that the present findings may be extended to the majority of normal, healthy elderly subjects, implying wide application for the questionnaire in the assessment of calcium intake in the elderly.     

Self-reported health problems among Swedish miners one year after unemployment

Unemployment is considered to be a public health concern sincedeterioration in the health of the unemployed is often anticipated.However, for some groups, such as miners, unemployment mightimprove health due to a cessation of potentially harmful occupationalexposures. This study evaluates the health of 79 miners in oneSwedish iron-ore mine, and 226 age-matched controls from thegeneral population, during one year after the closure of themine. The participants received a questionnaire regarding medicalhistory and subjective symptoms at the beginning of the studyperiod, and after one year. Statistically significant negativeeffects on self-reported health attributable to unemploymentwere not found, although neuropsychiatric symptoms were morecommon among the unemployed miners. The miners reported a statisticallysignificant improvement in grip force (p=0.031). They had asignificantly higher prevalence of symptoms associated withmining related exposures when compared with the population controls;pain in the upper extremities [relative risk (RR)=2.27, 95%confidence interval (Cl)=1.44–3.59), back pain (RR=1.84;Cl=1.237–2.75), vasospastic disease of the fingers (RR=2.05;Cl=1.18–3.57) and obstructive respiratory symptoms (attacksof dyspnea and wheezing: RR=3.67; Cl=1.167–11.6).     

Excès de cas humains et animaux de tularémie en France au cours de l’hiver 2007–2008 : émergence ou phénomène isolé ?

Context

Tularemia is a zoonosis affecting humans and hares in France. We describe the results of surveillance in both species, in 2007 and 2008.

Methods

Human tularemia cases are mandatorily notifiable in France since 2003. In hares, surveillance relies on volunteer hunter associations in all districts of the country. Data from mandatory reports and volunteer surveillance in 2007/2008 were analyzed and compared with previous results.

Results

In 2007/2008, 144 cases were reported in humans and 117 cases in hares. This was a 100% increase compared to previous years. Human cases differed from those of previous years only by the frequency of contact with breeding animals. Human cases without any documented risk exposure were also more frequent.

Conclusion

An increase of tularemia cases occurred in 2007/2008 in both species. Complementary studies are needed to identify the species reservoir in France to understand the causes of this peak of cases.     

Occupational health hazards in mining: an overview

This review article outlines the physical, chemical, biological, ergonomic and psychosocial occupational health hazards of mining and associated metallurgical processes. Mining remains an important industrial sector in many parts of the world and although substantial progress has been made in the control of occupational health hazards, there remains room for further risk reduction. This applies particularly to traumatic injury hazards, ergonomic hazards and noise. Vigilance is also required to ensure exposures to coal dust and crystalline silica remain effectively controlled.     

Manufacture and use of nanomaterials: current status in the UK and global trends

This paper provides an overview of the production and use of nanomaterials (NMs), particularly in the UK. Currently, relatively few companies in the UK are identifiable as NM manufacturers, the main emphasis being the bulk markets in metals and metal oxides, and some niche markets such as carbon nanotubes and quantum dots. NM manufacturing in the UK does not reflect the global emphasis on fullerenes, nanotubes and fibres. Some assumptions have been made about the types of NM that are likely to be imported into the UK, which currently include fullerenes, modified fullerenes and other carbon-based NMs including nanotubes. Many university departments, spin-offs and private companies have developed processes for the manufacture of NMs but may only be producing small quantities for research and development (R&D) purposes. However, some have the potential to scale up to produce large quantities. The nanotechnology industry in the UK has strong R&D backup from universities and related institutions. This review has covered R&D trends at such institutions, and appropriate information has been added to a searchable database. While several companies are including NMs in their products, only a few (e.g. manufacturers of paints, coatings, cosmetics, catalysts, polymer composites) are using nanoparticles (NPs) in any significant quantities. However, this situation is likely to change rapidly. There is a need to collect more information about exposure to NPs in both manufacturing and user scenarios. As the market grows, and as manufacturers switch from the micro- to the nanoscale, the potential for exposure will increase. More research is required to quantify any risks to workers and consumers.     

深圳公立医院管理体制改革制度设计

深圳公立医院管理体制改革实行政事分开、管办分开,在理事会架构下按法定机构模式组建市医管中心,落实公立医院运营管理自主权.作者从当前公立医院管理体制的弊端入手,介绍了深圳市进行公立医院管理体制改革的基本思路及改革方案设计的主要举措,深入剖析了的改革方案的特点,并对改革效果进行了预测.     

Effects of nitrogen dioxide on red blood cells of rats: Changes in components of red cell membranes during in vivo exposure to NO2

Red cell membranes, prepared from red blood cells of rats exposed to 4, 10, or 20 ppm nitrogen dioxide (NO₂) for 1 to 10 days, were examined for evidence of changes in membrane components. Appreciable changes were not found in contents of phospholipid and cholesterol during exposure to 10 ppm NO₂. By contrast, protein content altered with the time of exposure. Moreover, changes in protein composition were observed by employing sodium dodecyl sulfate — polyacrylamide gel electrophoresis. Twenty-four-hour exposure to NO₂ at the concentration above 10 ppm resulted in a marked increase in the percentage of lysophosphatidylethanolamine (LysoPE) to the total phospholipids. The prolonged exposure to 10 ppm NO₂ gave rise to a further increase in LysoPE, whereas the percentage of phosphatidylethanolamine (PE) showed a gradual decrease. A 1-day exposure to 4.0 ppm NO₂ also caused an increase in sialic acid content and decreases in those of PE and hexose. In addition to contents of these components the percentage of LysoPE increased 5 days after exposure and the elevated values were maintained up to the end of exposure period. These results demonstrate that red blood cells in circulation exhibit different membrane properties in terms of lipid and carbohydrate composition during 10 days of exposure to 4.0 ppm NO₂.     

Investigating clusters in the workplace and beyond

Clusters of disease are common and occur in the workplace and in the general community. They often arouse considerable concern among the population. Investigations have sometimes lead to exciting new knowledge, but in general the investigation of clusters is difficult and often unrewarding, especially for community clusters. In the workplace, investigations are more likely to find associations and even new causes, but still many clusters remain enigmatic. Despite this, there are many reasons for investigating clusters, including allaying community concern and identifying uncontrolled exposures. A structure for investigating clusters in the workplace is suggested.