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1.
目的:研究“钙激活的氯通道”成员之一gob-5和粘蛋白基因Muc5ac在小鼠哮喘模型肺部的表达。 方法: 22只清洁级BALB/c小鼠随机分成哮喘组和对照组,用逆转录聚合酶链反应法(RT-PCR)和免疫组化法分别测定肺组织gob-5 mRNA和粘蛋白基因Muc5ac蛋白的表达。 结果: 小鼠哮喘组肺组织gob-5 mRNA表达阳性(0.2297±0.0186,A),而对照组未出现gob-5 mRNA的表达(P<0.01);哮喘组Muc5ac蛋白表达(0.6637±0.0127,A)明显高于对照组(0.2060±0.0179,A)(P<0.01);哮喘组肺组织gob-5 mRNA表达与Muc5ac蛋白表达呈直线正相关(r=0.864, P<0.05)。 结论: Gob-5 mRNA表达的上调可能在哮喘小鼠气道粘液过度分泌中起着关键作用;抑制gob-5的表达将为哮喘的治疗提供新的策略。  相似文献   

2.
目的:探讨CCR3在哮喘小鼠气道黏蛋白5ac(Muc5ac)表达中的作用。方法:将50只清洁级BALB/c小鼠随机分为正常对照组、哮喘组、地塞米松干预组、SB328437干预组及溶剂对照组二甲基亚砜组,各10只。测定BALF中细胞总数、分类,ELISA检测IL-4、TNF-α,肺组织HE染色,免疫组化和RT-PCR检测Muc5ac、CCR3的表达。结果:在BALF细胞总数、嗜酸性粒细胞、单核细胞、淋巴细胞、IL-4,TNF-α水平、AB-PAS阳染面积、黏蛋白Muc5ac、CCR3蛋白IOD及Muc5ac mRNA、CCR3 mRNA表达方面,哮喘组与地塞米松干预组、SB328437干预组,具有统计学差异(P0.01或P0.05)。结论:SB328437可抑制肺组织CCR3表达,进而抑制Muc5ac的表达和分泌,从而控制气道炎症。  相似文献   

3.
目的:研究地塞米松对白细胞介素IL-13诱导的大鼠鼻黏膜mCLCA3和黏蛋白Muc5ac表达的影响,探讨其对变应性鼻炎黏液分泌的影响.方法:30只SD大鼠随机分成对照组、IL-13组、地塞米松组,用逆转录聚合酶链反应法(RT-PCR)和免疫组化法分别检测鼻黏膜mCLCA3 mRNA和Muc5ac蛋白的表达.结果:对照组大鼠鼻黏膜中mCLCA3 mRNA表达为0.000±0.000,IL-13组为0.319±0.121,两组比较差异有统计学意义(P<0.05);地塞米松组为0.144±0.105,IL-13组为0.319 ±0.121,两组比较差异有统计学意义(P<0.05);对照组大鼠鼻黏膜中Muc5ac蛋白的表达(0.300±0.145)与IL-13组(1.389±0.499)比较,差异有统计学意义(P<0.05);地塞米松组Muc5ac蛋白的表达(0.901 ±0.390)较IL-13组(1.389±0.499)明显减少(P<0.05).结论:IL-13能够上调mCLCA3 mRNA和Muc5ac在鼻黏膜的表达,地塞米松可下调mCLCA3 mRNA和黏蛋白Muc5ac表达.  相似文献   

4.
目的:研究糖皮质激素对白细胞介素(IL)-13诱导的小鼠肺组织黏蛋白基因Muc5ac表达的影响,探讨其对气道黏液分泌的作用。方法:24只清洁级BALB/c小鼠被随机分为对照组、IL-13组和地塞米松组。IL-13组于d1、d3和d5分别鼻腔滴入重组鼠IL-13 100μg/只;地塞米松组分别于小鼠首次鼻腔滴入IL-13(同上述方法)前24小时、1小时以及随后的连续4天(d0—d5,共6天)腹腔注射0.5mg/kg地塞米松;对照组不进行任何处理。收集支气管肺泡灌洗液(BALF)并计数嗜酸细胞;用RT-PCR和免疫组化法分别检测Muc5ac mRNA和蛋白在小鼠肺组织的表达。结果:IL-13处理后,Muc5ac mRNA和蛋白在肺部的表达以及BALF中的嗜酸细胞计数均显著高于对照组(均P〈0.01);经地塞米松处理后,除BALF中的嗜酸细胞计数外,Muc5ac mRNA和蛋白在肺部的表达较IL-13组无明显降低。结论:IL-13能够上调Muc5ac mRNA和蛋白在肺组织的表达,通过黏液诱导活性在气道黏液分泌中起重要作用;地塞米松可显著抑制IL-13诱导的肺组织嗜酸细胞浸润,但并不抑制黏液分泌。  相似文献   

5.
目的:研究温阳益气平喘方对支气管哮喘大鼠肺组织嗜酸粒细胞凋亡及相关基因蛋白Bcl-2和Bax表达的影响.方法:60只SD大鼠随机分为6组,即正常组、模型组、温阳益气平喘高剂量组、温阳益气平喘低剂量组、桂龙咳喘宁组,氨茶碱组,每组10只.除正常组外以卵蛋白致敏并吸入激发法制备大鼠支气管哮喘模型,各治疗组均从第1次哮喘激发开始(造模第3周)至处死前每天灌胃给药,激发并给药4周后处死大鼠.应用TUNEL法检测肺组织嗜酸粒细胞凋亡,免疫组织化学检测肺组织Bcl-2和Bax蛋白的表达.结果:温阳益气平喘方高低剂量组大鼠肺组织嗜酸粒细胞凋亡指数显著高于哮喘模型组(P<0.01和P<0.05),高低剂量组优于桂龙咳喘宁组(P<0.01),高剂昔组优于氨茶碱组(P<0.01);肺组织及气道壁中Bcl-2蛋白阳性细胞的比例显著低于哮喘模型组(P<0.01和P<0.05),高剂量组优于桂龙咳喘宁和氨茶碱组(P<0.01);Bax蛋白阳性细胞的比例显著高于哮喘模型组(P<0.01),高低剂量组优于桂龙咳喘宁组(P<0.01),高低剂量组优于氨茶碱组(P<0.01和P<0.05).结论:温阳益气平喘方可通过调节抑制凋亡基因bcl-2和促进凋亡基因bax蛋白的表达,促进肺内EOS凋亡,减少炎细胞浸润,减轻哮喘气道炎症.  相似文献   

6.
目的:探讨鱼腥草总黄酮对肺炎支原体感染小鼠肺组织Bcl-2、Bax蛋白与mRNA表达水平及血清炎症因子的影响及作用机制。方法:50只BALB/c小鼠随机分为对照组、模型组、鱼腥草总黄酮低、中和高剂量组(0.5、1.0、2.0 g/kg),滴鼻给予肺炎支原体。HE染色观察肺组织病理变化,Western blot法与RT-PCR法分别检测各组小鼠肺组织Bcl-2、Bax蛋白与mRNA表达水平,ELISA法检测各组小鼠血清炎症因子TNF-α、IFN-γ和IL-6水平。结果:与对照组相比,模型组小鼠肺湿重指数明显升高(P0.05),肺组织出现炎症病变,肺泡璧增厚、肺泡间隔变宽、可见炎症细胞浸润,肺组织Bcl-2蛋白与mRNA表达水平明显降低(P0.05),Bax蛋白与mRNA表达水平明显升高(P0.05),Bcl-2/Bax值明显降低(P0.05),血清TNF-α、IFN-γ和IL-6水平明显升高(P0.05)。与模型组相比,鱼腥草总黄酮低、中和高剂量组小鼠肺湿重指数明显降低(P0.05),炎症细胞浸润情况改善,肺组织Bcl-2蛋白与mRNA表达水平明显升高(P0.05),Bax蛋白与mRNA表达水平明显降低(P0.05),Bcl-2/Bax值明显升高(P0.05),血清TNF-α、IFN-γ和IL-6水平明显降低(P0.05)。结论:鱼腥草总黄酮可上调Bcl-2蛋白与mRNA表达,下调Bax蛋白与mRNA表达,降低炎症因子水平,减少细胞凋亡,对肺炎支原体感染小鼠起抗感染作用。  相似文献   

7.
目的探讨银杏叶制剂对在哮喘免疫学发病机制中起关键作用的T淋巴细胞部分生物学功能的影响.方法 14只SD大鼠随机分成哮喘和正常两组,每组7只.从每只大鼠外周血分离出T淋巴细胞进行分组培养,72 h后用RT-PCR检测各组IL-2、IL-4、IL-5 mRNA的表达量,Westernblot检测各组细胞膜与细胞浆蛋白激酶Cα(protein kinase C α,PKCα)的表达比率.结果 IL-2、IL-4、IL-5mRNA表达量在哮喘组分别为0.58±0.086、1.03±0.12、0.48±0.08,正常组分别为0.45±0.03、0.35±0.08、0.15±0.05,各因子两组间比较差异有统计学意义(P<0.01);哮喘组T淋巴细胞给予BN-52021干预后IL-2、IL-4、IL-5 mRNA的表达量明显下降(分别为0.49±0.05、0.55±0.09、0.27±0.05,P<0.05);正常组IL-2/IL-4 mRNA的比值为1.27±0.20,哮喘组为0.60±0.18,两组比较差异有统计学意义(P<0.01),其中哮喘组给予BN-52021干预后比值有所增大0.92±0.15,与未干预组比较有明显变化(P<0.01).哮喘PMA+BN-52021干预组IL-2、IL-4、IL-5 mRNA表达量分别为1.52±0.25、1.99±0.36、0.68±0.21,明显低于哮喘PMA干预组(P<0.05),而PMA+Ro31-8220组与PMA+Ro31-8220+BN-52021干预组比较差异无统计学意义(P>0.05).哮喘空白组PKCα在T淋巴细胞胞膜与胞浆的表达量比率为0.629±0.093,显著高于正常对照组(0.056±0.012,P<0.01),BN-52021干预后哮喘组比率较未干预组明显下降0.395±0.098(P<0.05),PMA+BN-52021干预组PKCα比率为0.719±0.163,较PMA干预组(1.28±0.28)低(P<0.05);哮喘各组T淋巴细胞胞膜与胞浆PKCα表达量的比率与IL-4 mRNA表达量的相关性分析(n=42,r=0.845,P<0.01)显示呈明显正相关.结论银杏叶制剂对体外培养的哮喘大鼠T淋巴细胞因子IL-2、IL-4、IL-5的分泌均具有抑制作用,而对IL-2分泌的抑制作用相对较弱;银杏叶制剂对哮喘大鼠T淋巴细胞胞膜与胞浆PKCα的表达量比率具有明显的下调作用.  相似文献   

8.
目的:探讨细胞凋亡与肺缺血再灌注损伤的关系以及人硫氧还蛋白对凋亡及其相关基因的影响。方法:健康清洁级Wistar大鼠84只,随机分为对照组、肺缺血再灌注1h、3h、5h组和人硫氧还蛋白干预1h、3h和5h组。复制肺缺血再灌注损伤模型。采用电子显微镜和原位缺口末端标记法观测肺组织细胞凋亡的变化和凋亡指数,免疫组化技术检测肺组织细胞Bcl-2、Bax及凋亡信号调节激酶1(ASK1)蛋白表达的变化。结果:肺缺血再灌注组肺组织细胞凋亡指数、ASK1、Bcl-2和Bax蛋白表达均显著高于对照组(均P0.01),超微结构呈严重损伤性改变。人硫氧还蛋白干预组ASK1、Bax的表达显著下降(均P0.01),Bcl-2的表达及Bcl-2/Bax比值显著上调(P0.05或P0.01),肺组织细胞凋亡指数也显著低于缺血再灌注组(P0.01)。肺组织细胞凋亡指数分别与ASK1、Bax蛋白之间均呈显著正相关(分别r=0.775、r=0.814;均P0.01);与Bcl-2/Bax蛋白呈显著负相关关系(r=-0.275,P0.05)。结论:Bcl-2/Bax比值下调启动的肺组织细胞凋亡可能参与了肺缺血再灌注损伤的发生。人硫氧还蛋白可能通过下调ASK1的表达,提高Bcl-2/Bax的比值减少肺组织细胞凋亡,从而减轻肺缺血再灌注损伤。  相似文献   

9.
过量饮酒对凋亡相关基因bcl-2、bax在生精细胞表达的影响   总被引:2,自引:0,他引:2  
目的 研究长期过量饮酒对凋亡相关基因bcl - 2、bax在睾丸及生精细胞中表达的影响。方法 利用人类饮用白酒制备大鼠的酒精毒性模型 ,采用免疫组织化学技术 ,检测酒精对Bcl- 2、Bax蛋白在睾丸及生精细胞表达的影响。结果 高剂量的酒精作用于大鼠 2个生精周期 ,每个生精小管中Bcl- 2蛋白表达的阳性细胞数目在高剂量组为 96± 33.74 ,低剂量组为 15 6 .6± 2 8.5 2 ,均显著低于正常对照组 (2 2 2 .6± 5 6 .86 ) (P <0 .0 1)。每个细胞中Bcl- 2蛋白表达强度 (OD值 )在高剂量组 (0 .14 2± 0 .0 35 )、低剂量组 (0 .15 1± 0 .0 2 6 ) ,都明显低于对照组 (0 .196± 0 .0 32 ) (P <0 .0 1) ;Bax蛋白表达的阳性细胞数在高剂量组为 (4 12 .4± 96 .75 ) ,低剂量组为 (337.5± 94 .39) ,均明显高于对照组 (2 14± 82 .5 7) (P <0 .0 1) ,Bax蛋白的表达强度 (OD值 )在高剂量组 (0 .113± 0 .0 36 )和低剂量组 (0 .0 82± 0 .0 17) ,均明显高于对照组 (0 .0 5± 0 .0 2 4 ) (P <0 .0 1)。结论 长期过量饮酒使睾丸及生精细胞中bcl- 2的表达降低 ,bax的表达增强。  相似文献   

10.
目的 探讨羌活提取物(EN)对哮喘小鼠Thl/Th2细胞平衡的影响,以及p38信号通路在其中的作用。 方法 60只雄性清洁级BABL/c小鼠,随机分为6组,每组10只,分别为正常对照组;卵蛋白(OVA)哮喘组;羌活低剂量组;羌活高剂量组、SB203580组和地塞米松组。在末次激发24 h后小鼠肺组织行HE染色。分别用ELISA检测支气管肺泡灌洗液 (BALF)中白细胞介素(IL)-4、IL-5、IL-13和γ-干扰素(IFN-γ)含量以及Western blotting检测肺组织IL-4、IFN-γ、P38蛋白表达。
结果 哮喘组小鼠与对照组小鼠相比较,BALF中炎症细胞计数、IL-4、IL-5、IL-13水平增高,而IFN-γ的表达明显降低(P<0.05),肺部炎症浸润明显(P<0.05);肺组织IL-4和磷酸化P38蛋白表达水平显著高于对照组(P<0.05),而肺组织IFN-γ的表达明显低于对照组(P<0.05)。羌活低、高剂量组、SB203580组和地塞米松组与哮喘模型组相比较,BALF中炎症细胞计数、IL-4、IL-5、IL-13浓度以及肺组织IL-4和磷酸化P38蛋白表达水平均显著降低(P<0.05);肺部炎症明显减轻(P<0.05);BALF和肺组织中IFN-γ明显升高(P<0.05)。 结论 羌活提取物具有明显的抗哮喘作用,其机制可能是通过抑制P38信号通路,影响Thl/Th2细胞平衡实现的。  相似文献   

11.
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   

12.
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   

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.
There are an estimated over 200 million yearly cases of malaria worldwide. Despite concerted international effort to combat the disease, it still causes approximately half a million deaths every year, the majority of which are young children with Plasmodium falciparum infection in sub-Saharan Africa. Successes are largely attributed to malaria prevention strategies, such as insecticide-treated mosquito nets and indoor spraying, as well as improved access to existing treatments. One important hurdle to new approaches for the treatment and prevention of malaria is our limited understanding of the biology of Plasmodium infection and its complex interaction with the immune system of its human host. Therefore, the elimination of malaria in Africa not only relies on existing tools to reduce malaria burden, but also requires fundamental research to develop innovative approaches. Here, we summarize our discoveries from investigations of ethnic groups of West Africa who have different susceptibility to malaria.  相似文献   

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16.
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   

17.
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   

18.
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   

19.
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   

20.
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   

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