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1.
健康雄性新西兰家兔28只,随机分为四组:正常对照组,缺氧组、氧反常组、DS-201氧反常组。离体心脏灌流造成心肌缺氧、氧反常模型。分离心肌线粒体,分光光度法测定线粒体内膜呼吸酶——琥珀酸脱氢酶(SDH)和细胞色素氧化酶(CCO)活力;氧电极法测定线粒体呼吸耗氧量,呼吸底物分别采用谷氨酸加苹果酸或琥珀酸。  相似文献   

2.
本实验分别以ESR自旋标记法、TBA比色法测定大鼠离体心脏缺血,再灌注时线粒体膜流动性及脂质过氧化物含量。发现心肌线粒体膜深层的流动性在缺血40分钟后有氧再灌注20分钟时(S=0.112±0.006、τ_e=7.13±0.09×10~(-10)sec)明显低于富氧灌注组(S=0.103±0.007、τ_e=6.86±0.20×10~(-10)sec),P<0.05;而脂质过氧化物含量再灌注组(3.02±0.68nmol/mgpr.)则极明显高于富氧灌注组(1.94±0.35nmol/mgpr.),P<0.01。预先给予丹参素,对以上变化有明显的改善作用,上述两项指标与富氧灌注组相比,无明显差别,P>0.05。另外,采用ESR自旋捕集技术发现丹参素对外源性O_2~-·有清除作用。因而推测,丹参素可能作为一种O_2~-·的清除剂保护心肌线粒体免受氧自由基引发的脂质过氧化损害。  相似文献   

3.
目的:探讨缺血预适应(ischemic preconditioning,IPC)对青年与老年大鼠缺血/再灌注(ischemia/reperfusion,IR)心肌损伤的影响。方法:雄性3月龄(青年)与20月龄(老年)Wistar大鼠,应用离体心脏灌流方法复制心肌IR与IPC模型。实验分为青年缺血/再灌注(YIR)组、青年缺血预适应(YPC)组、老年缺血再灌注(OIR)组与老年缺血预适应(OPC)组。透射电镜观察心肌及心肌线粒体超微结构变化;TTC染色测定心肌梗死面积;比色法测定冠脉流出液中乳酸脱氢酶(LDH)活性、心肌组织中超氧化物歧化酶(SOD)活性及丙二醛(MDA)含量;酶联免疫吸附法测定心肌组织硝基化与羰基化蛋白质含量,TUNEL方法检测心肌细胞凋亡;氧电极法测定线粒体呼吸功能及钙诱导的线粒体渗透性转运孔开放情况。结果:与YIR组比较,YPC组心肌梗死面积明显减少,冠脉流出液中LDH活性降低,心肌组织的SOD活性增加,MDA含量降低,心肌硝基化与羰基化蛋白含量降低。电镜下可见YPC组心肌及分离的心肌线粒体膜结构完整、基质致密。YIR组心肌线粒体呼吸控制率与Ⅲ态耗氧量及P/O比值均明显增加,质子漏出减少,钙诱导的线粒体肿胀明显减轻,心肌细胞凋亡率下降。而与OIR组比较,OPC组上述指标均无显著统计学差异。与YPC组比较,OPC组心肌超微结构损伤明显增加,心肌氧化应激水平增加,线粒体呼吸功能下降,心肌细胞凋亡与坏死增多。结论:缺血预适应能够保护青年大鼠心肌缺血/再灌注损伤;而老年大鼠心脏对预适应刺激减敏,导致缺血预适应心肌保护作用钝化,这可能与老龄IPC心脏氧化应激水平增加导致线粒体损伤、细胞凋亡有关。  相似文献   

4.
本研究用成年雄性Wistar大鼠,作肾缺血和再灌注实验;发现:(1)缺血60分钟组的肾皮质脂质过氧化物含量(MDA76.05±18.14nmol/g)显著降低(P<0.001),钠浓度(97.43±10.20mEq/L)显著增高(P<0.01)而钾浓度(74.68±6.36mEq/L)显著降低(P<0.002)。(2)缺血60分钟再灌注30分钟组的肾皮质,脂质过氧化物含量(147.25±17.18nmol/g)显著增加(P<0.01),钠、钾浓度接近正常值(79.61±18.44和90.33±6.13mEq/L)。缺血与缺血再灌注肾皮质其脂质过氧化物含量同钠钾浓度之间无显著相关。实验提示:(一)缺血再灌注肾氧自由基“爆发性”生成所引发的脂质过氧化可能是肾缺血后损伤的重要机制之一。(二)缺血肾内钠、钾浓度变化似能反映缺血引起的细胞膜钠泵失灵及细胞内外离子分布异常。这种变化同氧自由基生成和脂质过氧化强度之间,似无直接因果关系。  相似文献   

5.
缺氧预处理对自发性高血压大鼠心肌细胞内钙的影响   总被引:2,自引:2,他引:0  
目的:探讨缺氧预处理对后继缺氧再给氧所致心肌细胞内钙超载的影响及蛋白激酶C(PKC)和百日咳毒素(PTX)敏感的G-蛋白在缺氧预处理的作用.方法:循环灌流法分离自发性高血压大鼠(SHR)肥大心肌细胞,用Fu ra-2AM测定钙浓度.结果:[Ca2+].为1.0 mmol/L时,预处理组缺氧再给氧后其心肌细胞内游离钙浓度[Ca2+]i为(194.0±24.8) nmol/L,未预处理组为(297.5 ±24.5) nmol/L;无外钙预处理组缺氧再给氧后其心肌细胞[Ca2+]i为(162.0 ±30.7) nmol/L,未预处理组为(236.5±28.3) nmol/L,提示缺氧预处理可减少缺氧再给氧所致心肌细胞内钙释放及外钙内流.在[Ca2+].为1.0 mmol/L组,于预处理前分别预先给予PKC拮抗剂Staurosporine(10 nmol/L)及Gi-蛋白失活剂百日咳毒素(PTX,200 ng /L),可见经后继缺氧再给氧后其心肌细胞[Ca2+]i分别为(264.8±19.3)及(25 8.0±27.7) nmol/L,高于缺氧预处理组但低于未预处理组.结论:SH R肥大心肌细胞,缺氧预处理可减轻后继缺氧再给氧所致心肌细胞内钙超载;PKC及PTX敏感的G- 蛋白可能部分参与缺氧预处理的保护作用.  相似文献   

6.
高浓度氧对沙土鼠脑缺血再灌流后脂质过氧化作用的影响   总被引:1,自引:0,他引:1  
沙土鼠双侧颈总动脉结扎1小时后,于高氧环境中再灌流2小时,脑MDA含量(4.39±0.26nmol/mg蛋白)与空气对照组(2.63±0.50nmol/mg蛋白)、高氧对照组(3.07±0.52nmol/mg蛋白)、缺血组(2.96±0.41nmol/mg蛋白)及空气中再灌流组(2.79±0.59nmol/mg蛋白)相比较,差异均具有高度显著性(P<0.01)。大脑皮层TXB_2含量增加,6-Keto-PGF_(1α)含量减少,水、钠含量明显增加。但上述各指标与缺血后在大气环境中再灌流组相比,差异均无显著性。作者推测,高浓度氧导致脂质过氧化作用增强的机理可能源于异常的线粒体电子传递链功能。  相似文献   

7.
目的 探讨增加不饱和脂肪酸摄入比例对心脏ω-6/ω-3多不饱和脂肪酸(PUFAs)比值及心肌缺血-再灌注时缺血区炎症状态及线粒体功能的影响.方法 C57BL/6小鼠80只,随机分为普通饮食组及植物油脂组(n=40).喂养1个月后,建立心脏缺血再灌注模型.气相色谱法检测心脏ω-3及ω-6 PUFAs含量.TTC染色检测心肌梗死面积.差速离心法分离心肌线粒体,氧电极法测定线粒体呼吸控制率.实时定量PCR检测缺血区心肌肿瘤坏死因子-α(TNF-α) mRNA表达,ELISA法检测心肌TNF-α及白细胞介素-1(IL-1)蛋白含量.结果 与普通饮食组相比,植物油脂组小鼠心脏ω-6/ω-3 PUFAs比值显著减低(P<0.05),心肌梗死面积显著减小(P<0.01),缺血区心肌线粒体呼吸控制率显著改善(P<0.05),TNF-αmRNA表达、TNF-α及IL-1蛋白含量均显著降低(P<0.05).结论 不饱和脂肪酸改善小鼠心肌脂质成分及缺血再灌注后线粒体功能.  相似文献   

8.
目的:探讨urocortin-I预处理对离体大鼠缺血再灌注心肌线粒体呼吸功能及酶活性的影响,观察心肌细胞ATP含量的变化。方法:(1)健康雄性SD大鼠随机分为4组:正常组(Nor组)、缺血再灌注组(IR组)、urocortin-I预处理组(Ucn I组)、5-羟葵酸(5-HD)拮抗urocortin-I组(5-HD+Ucn I组)。采用Langendorff装置建立大鼠离体心脏缺血再灌注模型。分别于平衡末(T_1)、缺血前(T_2)及再灌注末(T_3)分离、提取心肌线粒体,测定各组线粒体呼吸功能及呼吸酶活性。(2)利用MPA离体心脏灌注装置分离成年大鼠心肌细胞,将分离培养24 h后同批次的心肌细胞随机分为正常组(Nor组)、缺氧复氧组(I/R组)、urocortin-I预处理组(Ucn I组)、5-HD拮抗urocortin-I组(5-HD+Ucn I组)。建立缺氧复氧模型,于复氧末用高效液相色谱法检测各组心肌细胞ATP含量。结果:T_3时点除Nor组外,其余各组与T_1、T_2时点相比呼吸功能(3态呼吸速率、呼吸控制率)及琥珀酸氧化酶、NADH氧化酶、细胞色素C氧化酶活性均明显下降(P0.05);T_3时Ucn I组心肌线粒体的呼吸功能及呼吸酶活性明显优于5-HD+Ucn I组及IR组(P0.05),但次于Nor组(P0.05);T_3时5-HD+Ucn I组心肌线粒体的呼吸功能及呼吸酶活性(琥珀酸氧化酶、NADH氧化酶)较IR组好(P0.05),但2组间细胞色素C氧化酶活性差异无统计学显著性;T_1、T_2时点各组组内及组间呼吸功能及3种呼吸酶活性的差异无统计学显著性。心肌细胞实验结果显示,复氧末Nor组ATP含量较其余各组均高(P0.01);I/R组和5-HD+Ucn I组心肌细胞的ATP含量较Ucn I组低(P0.05);此外,5-HD+Ucn I组心肌细胞的ATP含量较I/R组高(P0.05)。结论:Ucn I预处理可减轻缺血再灌注对心肌线粒体呼吸功能及呼吸酶活性的干预,保证了缺氧/复氧后心肌ATP的含量。  相似文献   

9.
目的 研究3种不同预处理对在体大鼠缺血再灌注心肌的保护作用及αB晶状体蛋白在不同预处理心肌细胞缺血再灌注损伤中的变化.方法 24只SD大鼠按完全随机法分成4组,每组6只,分别为缺血再灌注组、缺血预处理组、腺苷预处理组、远程预处理组.建立大鼠在体缺血再灌注损伤模型,观察各组缺血再灌注前后心功能变化,并检测冉灌注末血清肌钙蛋白T(cTnT)、丙二醛(MDA)、超氧化物歧化酶(SOD)的变化以及心肌组织αB品状体蛋白的表达.结果 心肌缺血再灌注120 min后,与缺血再灌注组比较,其余3组左心室室内压最大上升和下降速率(±dp/dt_(max))均明显升高(均P<0.05).缺血预处理组、腺苷预处理组、远程预处理组血清cTnT含量均低于缺血再灌注组[(12.898±2.887)、(5.049±4.387)、(7.049±4.387)μg/L比(22.902±3.146)μg/L,均P<0.05];MDA含量也均低于缺血再灌注组[(10.648±3.635)、(11.736±8.903)、(9.834±6.128)μmol/L比(16.083±10.423)μmol/L,均P<0.05];SOD含量均高于缺血再灌注组[(82.808±22.407)、(162.266±54.128)、(102.266±34.134)U/ml比(76.757±39.446)U/ml,均P<0.05].腺苷预处理组SOD含量高于缺血预处理组和远程预处理组;cTnT含量则低于缺血预处理组(均P<0.05).与缺血再灌注组比较,其余3组αB晶状体蛋白表达均显著增高(均P<0.05).结论 腺苷预处理、远程预处理均可以模拟缺血预处理的心肌保护作用.3种预处理可能通过上调αB晶状体蛋白表达从而减轻在体大鼠心肌缺血再灌注损伤.  相似文献   

10.
目的: 观察胰高血糖素样肽-1(GLP-1)对大鼠心肌缺血再灌注/细胞缺氧复氧损伤的作用并探讨其机制。方法: 建立大鼠缺血再灌注模型,分别设假手术组(sham)、缺血再灌注组(IR)和IR + GLP-1(0.030 nmol/L、0.16 nmol/L和0.30 nmol/L)组,缺血30 min后再灌注3 h,Evan’s blue-TTC法检测心肌梗死范围;取左心室游离壁心肌组织,TUNEL法检测心肌细胞凋亡,同时测定心肌组织中氧化-抗氧化物质超氧化物歧化酶(SOD)活性及丙二醛(MDA)含量;培养乳鼠心肌细胞,随机分为正常对照组(control)、单纯缺氧复氧组(HR)、HR + GLP-1(1 μmol/L、5 μmol/L和10 μmol/L)组,电镜下观察心肌细胞形态的变化,流式细胞术检测心肌细胞的凋亡,测定乳酸脱氢酶(LDH)释放、SOD活性、MDA含量、活性氧簇(ROS)水平以及线粒体膜电位(MMP)。结果: 与IR组相比,IR+GLP-1(0.03 nmol/L、0.16 nmol/L和0.30 nmol/L)组剂量依赖性地减小心肌梗死面积,减轻线粒体超微结构改变及细胞凋亡,增加SOD活性,减少MDA含量(P<0.05 或P<0.01);与HR组相比,HR+GLP-1(1 μmol/L、5 μmol/L和10 μmol/L)组剂量依赖性地逆转HR诱导的细胞损伤,增加SOD活性,减少MDA含量,降低ROS水平,减轻HR诱导的MMP降低(P<0.05或P<0.01)。结论: GLP-1可以减轻大鼠心肌缺血再灌注/细胞缺氧复氧损伤;其作用机制可能与增强心肌抗氧化能力及保护线粒体结构和功能有关。  相似文献   

11.
Over 200 schizophrenic patients belonging to three major and interrelated pedigree complexes have been investigated over the past 30 years in a North Swedish geographically isolated population, presently numbering about 6,000. An intensive investigation of a number of biochemical correlates and genetic markers in a few selected families belonging to one of the major pedigrees has indicated new strategies for the current research program.
Schizophrenia, as defined operationally, is significantly associated with decreased activities of two enzymes (1) blood platelet monoamine oxidase, (2) plasma dopamine-β-hydroxylase, and (3) with the genetic marker Gc2 (group specific antigen). Both enzymes are subject to genetic variation. A positive score for linkage between schizophrenia and low plasma DBH activity has been calculated, but, so far, available data are insufficient for discrimination between linkage and partial contribution of genetically controlled low plasma DBH to the pathogenesis of the disease. Alternatively, both mechanisms could be involved.
As a model for continued research, schizophrenia is explained as based on a double dominant-recessive genotype (Aabb), representing a vulnerability which in about 50 % of cases develops into clinical schizophrenia. It is suggested that the dominant mutation (A) operates on or affects MAO activity, and that the recessive genotype (bb) is instrumental in low variates of DBH activity and very likely such variates within the normal range of physiological variation. Moreover, it is suggested that the combined effects of MAO- and DBH-reduced efficiency on the metabolism of e.g. dopamine could be an essential pathogenic mechanism for the schizophrenic illness which is segregating in this population.  相似文献   

12.
Renal dysplasia and asplenia in two sibs   总被引:2,自引:0,他引:2  
A family is reported in which two sibs, one male and the other female, both died within 24 hours of birth with enlarged polycystic kidneys. Postmortem histology in the second child showed gross renal dysplasia. In both children the pancreas was enlarged, nodular and cystic but the liver appeared macroscopically normal. In the second child, histological examination confirmed pancreatic fibrosis with cystic dilation of ducts, but showed portal fibrosis with bile duct proliferation in the liver.
This combination of findings is very reminiscent of those in a girl and her brother reported by Ivemark et al. (1959). The children reported here also showed absence or hypoplasia of the spleen, cardiac anomalies and other features of the Ivemark syndrome (Ivemark 1955), a quite different, usually sporadic, congenital disorder. It is suggested that the children described here have a distinct lethal congenital disorder, probably inherited in an autosomal recessive manner.  相似文献   

13.
About 1900, modern food selection and processing caused widespread epidemics of the B vitamin deficiency diseases of beriberi and pellagra which, for genetic reasons, often expressed as different diseases ranging from bowel and heart disease to dermatoses and psychoses. But the B vitamins merely help convert essential fatty acids (EFA) into the prostaglandin (PG) tissue regulators and it now turns out that, through hydrogenation, milling and selection of w3-poor southern foods, we have also been systematically depleting, by as much as 90%, a newly discovered trace Nordic EFA (w3) of special importance to primates and sole precursor of the PG3(4) series, even as a concurrent fiber deficiency increases body demand for EFA. Since substrate EFA is processed by many B vitamin catalysts, an EFA deficiency will mimic a panhypovitaminosis B, i.e., a mixture of substrate beriberi and substrate pellagra resembling vitamin beriberi and pellagra but exhibiting as even more diverse endemic disease. This would consitute a second stage of the Modern Malnutrition and explain why some workers now hold the dominant diseases of modermized societies to be new, nutritionally based, pellagraform yet lipid-related and to range, once again, from heart disease to psychosis. It is an assumption that our dominant diseases are unrelated to each other or are merely revealed by our diagnostic acumen and therapeutic success; and that hydrogenating millions of tons of food oils annually, to destroy the rancidity producing w3-EFA, is safe for primates. Extensive beriberiform disease is reported here in 32 typical cases taken from medical practice which responds strikingly to linseed oil supplements (60% w3-EFA) in confirmation of identical results in Capuchins.  相似文献   

14.
15.
Newton H 《Medical history》2011,55(2):153-182
Sick children were ubiquitous in early modern England, and yet they have received very little attention from historians. Taking the elusive perspective of the child, this article explores the physical, emotional, and spiritual experience of illness in England between approximately 1580 and 1720. What was it like being ill and suffering pain? How did the young respond emotionally to the anticipation of death? It is argued that children’s experiences were characterised by profound ambivalence: illness could be terrifying and distressing, but also a source of emotional and spiritual fulfilment and joy. This interpretation challenges the common assumption amongst medical historians that the experiences of early modern patients were utterly miserable. It also sheds light on children’s emotional feelings for their parents, a subject often overlooked in the historiography of childhood. The primary sources used in this article include diaries, autobiographies, letters, the biographies of pious children, printed possession cases, doctors’ casebooks, and theological treatises concerning the afterlife.  相似文献   

16.
Recent advancements in agricultural biotechnology have created a need for analytical techniques to determine introduced proteins in crops enhanced through modern biotechnology techniques. These proteins are expressed in plant tissues and may be present in food ingredients. Immunoassays are ideally suited for protein detection and may be used as both quantitative and threshold methods. Microplate ELISA and lateral flow devices are two of the most commonly used immunoassay formats for agricultural biotechnology applications. This paper provides general background information and a discussion of criteria for the validation and application of immunochemical methods to the analysis of proteins introduced into plants and food ingredients using biotechnology methods. It is the result of a collaborative effort of members of the Analytical Environmental Immunochemical Consortium. This collaborative effort represents the combined expertise of several organizations to reach consensus on establishing guidelines for the validation and use of immunoassays. Further, the paper offers developers and users a consistent approach to adopting the technology as well as aid in producing accurate and meaningful results.  相似文献   

17.
HLA-A,-B,-C,-DRB1 and -DQB1 alleles have been studied in Chimila Amerindians from Sabana de San Angel (North Colombian Coast) by using high resolution molecular typing. A frequent extended haplotype was found:HLA-A*24:02-B*51:10-C*15:02-BRB1*04:07-DQB1*03:02 (28.7%) which has also been described in Amerinndian Mayos Mexican population (Mexico, California Gulf, Pacific Ocean). Other haplotypes had already been found in Amerindians from Mexico (Pacific and Atlantic Coast), Peru (highlands and Amazon Basin), Bolivia and North USA. A geographic pattern according to HLA allele or haplotype frequencies is lacking in Amerindians, as already known. Also, five new extended haplotypes were found in Chimila Amerindians. Their HLA-A*24:02 high frequencies characteristic is shared with aboriginal populations of Taiwan; also, HLA-C*01:02 high frequencies are found in New Zealand Maoris, New Caledonians and Kimberly Aborigines from Australia. Finally, this study may show a model of evolutionary factors acting and rising one HLA allele frequency (-A*24:02), but not in others that belong to the same or different HLA loci.  相似文献   

18.
The preparation steps usually necessary for obtaining ultrathin frozen sections of biological material (chemical prefixation, enclosing, cryoprotective treatment, freezing, sectioning, and post-staining the sections for transmission electron microscopy) are submitted to a critical analysis. The application of cryo-ultramicrotomy, in particularly for cytochemical purposes, is reviewed. Fundamental considerations of chemical prefixation and poststaining are supported by examples from yeast cytology. Furthermore, the efficiency of the cryo-ultramicrotomy (electron optical resolution of ultrastructural details) is demonstrated on yeast cells and protoplasts.  相似文献   

19.
Starting with the integument, we see many organs are contractile sacs or multiples thereof, which tubes or bags constitute the major part of the entire body. Recognition of this basic unit and its characteristics sheds new light, individually and collectively, on many disorders previously considered unrelated. Muscular tears and perforations develop in the walls of these chambers, being no way peculiar to those organs, wherein, hydrochloric acid occurs. So, it is not necessary to explain the absence of excessive acid from patients who exhibit holes in the gastric, uterine, aortic, duodenal, rectal, pulmonary, retina, and other walls. Muscle, not acid is the great common factor relating idiopathic disorders in the gastrointestinal tract to each other and to similar diseases in other systems. When the units are linked together, the lesions tend to appear as arthropathies, i.e. at the joints. Rephrasing common-place observations, frees us from conventional, conceptual cul-de-sacs. An observation is only as good as its interpretation, so all possibilities must be considered, otherwise, we will remain blinded by our misconceptions.  相似文献   

20.
Zusammenfassung Der Einfluß von verschiedenen Nahrungsmitteln auf Methoden zur Bestimmung von Adrenalin (AD), Noradrenalin (NA), Vanillinmandelsäure (VMS), Metanephrinen (MN), Homovanillinsäure (HVS) und 5-Hydroxyindolessigsäure (5-HIE) im 24 h-Harn zur Diagnose des Phäochromozytoms bzw. Karzinoid-Syndroms wurde untersucht. Die in die Untersuchung einbezogenen Nahrungsmittel waren: Tee, Kaffee, Mandeln, Ananas, Käse, Walnüsse, Vanillepudding, Bananen, Tomaten und Milchschokolade. Außerdem wurde der Einfluß des Zigarettenrauchens auf die Bestimmung von AD, NA, VMS und MN untersucht.Walnüsse führten zu einer starken Erhöhung der 5-HIE-Ausscheidung. Bananen erhöhten die Ausscheidung von AD, NA, VMS, MN und 5-HIE. Kaffee und Ananas bewirkten eine geringe Zunahme der MN-Werte. Rauchen von 20–30 Zigaretten/Tag beeinflußte keine der vier Variablen.Wenn die beschriebenen Methoden benutzt werden, sollte lediglich auf den Verzehr von Bananen und Walnüssen vor und während der Harnsammelperioden verzichtet werden, da die oberen Normgrenzen im Harn überschritten werden könnten. Ein Verzicht auf Kaffee und Ananas in normalen Mengen ist nicht erforderlich. Es besteht kein Anlaß, weiterhin die bisherigen umfangreichen Restriktionen der übrigen Nahrungsmittel beizubehalten.  相似文献   

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