川崎病发病机制研究进展

川崎病的发病机制一直没有完全清楚。但最近由于分子生物学的进步和人类基因组项目的完成,使得川崎病的发病机制有了重大的突破。本文就川崎病发病机制的研究进展做一综述。     

锌缺乏对生长期大鼠小肠黏膜形态和消化酶活性的影响

目的 了解锌缺乏对大鼠小肠黏膜形态和消化酶活性的影响.方法 3周龄刚断乳SD雄性大鼠30只,随机分成3组,每组10只:正常组自由食用含锌30μg/g正常饲料;缺锌组自由食用含锌0.4μg/g的缺锌饲料(参照AIN-76配方);配饲组食用正常饲料,但进食量限制为缺锌组大鼠前1天的进食量,各组自由饮用去离子水.每日清晨称大鼠体重并记录前1天的进食量,观察有无厌食、腹泻、皮炎、生长迟缓等缺锌的症状.2周后处死,检测血清锌的浓度;留取空肠黏膜作病理切片和HE染色,测定空肠黏膜绒毛高度和隐窝深度的比例;检测空肠黏膜刷状缘乳糖酶、γ谷氨酰转肽酶(GGT)和氨基寡肽酶(APN)的活性.结果 实验开始时正常组、缺锌组、配饲组大鼠的平均体重分别为(67.4±5.3)g、(64.7±4.8)g和(66.5±4.1)g,平均日进食量分别为(11.2±1.0)g、(11.6±1.6)g和(11.2±1.4)g,差异均无统计学意义.实验第7天缺锌组平均进食量与正常组和配饲组差异不明显,而平均体重则明显低于正常组和配饲组(P＜0.01);而2周实验结束时缺锌组平均体重为(112.0±11.5)g,明显低于正常组和配饲组的(164.0±15.9)g、(137.5±16.2)g;缺锌组平均进食量(13.4±5.1)g明显低于正常组的(18.2±2.4)g,差异有统计学意义(P均＜0.01).缺锌组血清锌的含量(733±231)μg/L明显低于正常组的(1553±159)μg/L和配饲组的(1457±216)μg/L(P＜0.01).三组大鼠空肠黏膜绒毛高度与隐窝深度比例分别为(2.98±0.5)、(2.77±0.5)和(2.81±0.7);乳糖酶活性分别为(26.1±15.0)U/mg、(27.4±12.8)U/mg和(40.8±18.5)U/mg,差异均无统计学意义.缺锌组空肠黏膜GGT为(12.7±6.5)U/g明显低于正常组的(19.1±10.4)U/g和配饲组的(18.5±7.7)U/g,但差异无统计学意义;缺锌组空肠黏膜APN(25.5±7.5)U/g明显低于正常组的(48.7±16.8)U/g和配饲组的(43.9±14.5)U/g,差异有统计学意义(P＜0.01).结论 锌缺乏可致食欲下降、体重减轻,可引起空肠黏膜刷状缘肽酶活性下降,但对绒毛高度与隐窝深度的比例和乳糖酶活性影响不大,表明锌缺乏最先影响的可能是蛋白质的消化与吸收功能.

Abstract：

Objective In this study,a growing rat model of zinc deficiency was established to investigate the effect of zinc deficiency on intestinal mucosal morphology and digestive enzyme activity as well as to provide a scientific basis for zinc supplementation therapy in patients with diarrhea.Method Threeweek-old weaned Sprague-Dawley male rats(n =30)were randomly divided into 3 groups with 10 in each:rats in the control group(ZA)were fed with a normal diet containing 30 μg/g zinc; rats in the zinc deficient group(ZD)were fed with a zinc-deficient diet containing 0.4 μg/g zinc(refer to AIN-76 formula); and rats in the paired fed group(PF)were fed with a normal diet,but the food intake was limited to intake of rats in ZD group in the previous day.All rats were provided with deionized water for drinking.Their body weight was measured and the food intake during the previous day was recorded early in the morning of the following day.Symptoms of zinc deficiency,such as anorexia,diarrhea,dermatitis,and growth retardation,were observed. Two weeks later,the rats were sacrificed and serum zinc concentration was measured.Jejunal mucosa was taken for biopsy and was stained with hematoxylin and eosin(HE).The height ratio of the jejunal mucosal villi and crypts was measured.In addition,the activity of lactase in the jejunal mucosal brush border,γ-glutamyl peptidase(GGT),and aminopeptidase N(APN)were measured.Result The average weight of the rats in the ZA,ZD,and PF groups at the beginning of the experiment was(67.4±5.3)g,(64.7±4.8)g,and(66.5±4.1)g,respectively,and the average daily food intake was (11.2±1.0)g,(11.6±1.6)g,and(11.2±1.4)g,respectively.The intergroup differences were not significant.On the 7th day of experiment,no significant differences in average food intake were observed between the ZD group and the ZA and PF groups,but the average body weight in the ZD group was significantly lower than that in the ZA and PF groups(P＜0.01).At the end of the experiment(2 weeks),the average weight in the ZD group(112.0±11.5)g was significantly lower than that in the ZA(164.0±15.9)g and PF groups(137.5±16.2)g.The average food intake in the ZD group(13.4±5.1)g was significantly lower than that in the ZA group(18.2±2.4)g(P＜0.01).Serum zinc level in the ZD group(733±231)μg/L was significantly lower than that in the ZA(1553±159)μg/L and PF groups (1457±216)μg/L(P＜0.01).The height ratio of jejunal mucosa villus and crypt in the ZA,ZD,and PF groups was 2.98±0.5,2.77±0.5,and 2.81±0.7,respectively,and lactase activity was(26.1±15.0)U/mg,(27.4±12.8)U/mg,and(40.8±18.5)U/mg,respectively,without significant intergroup differences.The GGT activity in the jejunal mucosa in the ZD group(12.7±6.5)U/g was significantly lower than that in the ZA(19.1±10.4)U/g and PF groups(18.5±7.7)U/g,but the difference was not significant.The activity of APN in the jejunal mucosa in the ZD group(25.5±7.5)U/g was significantly lower than that in the ZA(48.7±16.8)U/g and PF groups(43.9±14.5)U/g(P＜0.01).Conclusion Zinc deficiency can cause loss of appetite,weight loss,and decreased activity of peptidase in the jejunal mucosal brush border.Zinc deficiency has little effect on the height ratio of the villus and crypt and lactase activity,thereby indicating that zinc deficiency may first affect protein digestion and bsorption.     

建立雄性营养性肥胖幼鼠模型的研究

目的建立一种适合于研究儿童营养性肥胖的幼年大鼠肥胖模型。方法运用过度喂养造成高能量饮食新生大鼠肥胖模型,将出生第3天的雄性SD新生大鼠,随机分为对照组和模型组,模型组3只一笼,对照组10只一笼,分别由母鼠喂养至21 d,断乳后正常食料喂养,60 d后,随机6只一组,观察各组体质量、附睾及肾周脂肪质量,同时测定各组动物血糖、血脂、胰岛素等相关肥胖指标。结果出生21 d时,模型组较对照组体质量、体脂比、Lee′s指数明显增加(P<0.01或P<0.05,t值分别为-13.93,-5.12,-2.73,-4.87),血胰岛素分泌和胰岛素敏感指数均较对照组高(P<0.01,t值分别为-10.22,12.03),血糖和血脂无明显差异(P>0.05),出生后60 d,模型组较对照组体质量、体脂比、Lee′s指数明显增加(P<0.01,t值分别为-10.55,-5.53,-3.93,-5.99),血胰岛素分泌和胰岛素敏感指数、血糖和血脂均明显升高(P<0.01或P<0.05,t值分别为-2.26,-9.03,9.73,-5.47)。结论通过调整新生仔鼠只数,出生后21 d可诱导建立幼年雄性SD大鼠营养性肥胖模型,出生后60...     

嗜酸性粒细胞增多的儿童播散性念珠菌病1例

目的 探讨儿童播散性念珠菌病的临床表现及其与嗜酸性粒细胞增多之间的关系,为临床早期诊断提供有效思路。方法 回顾分析1例以嗜酸性粒细胞增多为特点的儿童播散性念珠菌病的病例资料、诊治过程及预后。结果 通过临床综合分析及真菌相关检测、脑脊液真菌培养最终确诊为播散性念珠菌病,经抗真菌治疗后好转出院。结论 播散性念珠菌病临床表现复杂多样无特异性,且发病隐匿,加之儿童病例许多无明确宿主因素,及易误诊。嗜酸性粒细胞增多与真菌感染存在一定联系。     

IL-2、IL-2Rα及IFN-γ基因多态性与汉族儿童支气管哮喘的关联

目的探讨IL-2(rs6822844)、IL-2Rα(rs2104286)及IFN-γ(rs2430561)多态性位点与汉族儿童支气管哮喘的关联。方法选取144例汉族支气管哮喘患儿为研究组,并以性别、年龄配对的228例汉族无支气管哮喘儿童作为对照组。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术检测IL-2(rs6822844)、IL-2Rα(rs2104286)及IFN-γ(rs2430561)的等位基因及基因型;采用实时荧光PCR检测对照组IL-2Rα各基因型外周血IL-2RαmRNA相对表达量,采用ELISA检测其各基因型血浆sIL-2Rα水平。结果IL-2Rα(rs2104286)位点等位基因A在研究组分布频率（86.8%）高于对照组（79.4%）（OR=1.708,95%CI：1.113~2.629,P=0.010）;研究组中AA基因型患者分布频率（75.0%）高于对照组（62.3%）（OR=1.745,95%CI：1.058~2.884,P=0.021）;未发现IL-2(rs6822844)位点有多态性分布,IFN-γ(rs2430561)位点等位基因及基因型频率在两组中分布差异均无统计学意义（P=0.182、0.205、0.421）。研究组中IL-2Rα(rs2104286)位点AA基因型个体外周血IL-2RαmRNA相对表达量以及血浆sIL-2Rα水平均显著高于AG基因型（P=0.043、0.018）。结论IL-2Rα(rs2104286)位点可能与汉族儿童支气管哮喘发生相关,而且该位点可能影响其转录表达。     

儿童自发性硬脊膜外血肿一例

患儿,男,6岁.因突发背部疼痛3 d,双下肢无力半天来院就诊,门诊以"格林巴利综合征?急性脊髓炎?"收入儿科治疗.患儿无发热、无排尿异常,病前无明显外伤史、无腹泻史.     

吡拉米司特在大鼠急性肺损伤模型中降低PDE4活性与TNF-α/IL-10平衡有关

目的观察PDE4活性与TNF-α/IL-10平衡在脂多糖(LPS)诱导的大鼠急性肺损伤模型(ALI)中相互关系,探讨选择性磷酸二酯酶4抑制剂吡拉米司特(piclamilast)对ALI的作用及机制。方法脂多糖(LPS)诱导大鼠ALI模型,设对照组、模型组、吡拉米司特组(1、3、10mg.kg-1)和地塞米松组(1mg.kg-1),常规细胞形态学检测肺泡灌洗液(BALF)和肺组织中中性粒细胞的浸润情况,比色法测定BALF中超氧阴离子自由基(O2.)和中性粒细胞髓过氧化酶(MPO),ELISA法检测肺组织中TNF-α和IL-10含量,高效液相(HPLC)法测定肺组织中PDE4活性。结果①吡拉米司特(1、3、10mg.kg-1)灌胃给予能够抑制BAL中MPO、O2.的增加,改善LPS诱导的大鼠ALI模型BALF中的炎症细胞聚集和肺水肿程度,②吡拉米司特可抑制LPS诱导的大鼠ALI肺组织TNF-α上升(P<0.05～0.01),并能明显提高LPS引起的大鼠ALI肺组织IL-10分泌下降,③大鼠ALI模型肺组织中PDE4活性明显上升(P<0.01),吡拉米司特预处理可抑制PDE4活性的上升,而且其对PDE4活性抑制性变化与TNF-α/IL-10比值的变化基本一致。地塞米松1mg.kg-1也能降低TNF-α和升高IL-10水平,调节TNF-α/IL-10平衡关系,但DXM不能抑制PDE4活性的升高。结论TNF-α/IL-10可能是ALI病理生理学的一对重要的平衡性细胞因子。吡拉米司特可能通过抑制PDE4活性,调节TNF-α/IL-10平衡改善LPS诱导的大鼠ALI。     

心脏肌浆网钙转运蛋白基因表达与调节

心肌细胞肌浆网钙转运蛋白通过调节细胞内游离钙浓度对心肌细胞的收缩,舒张功能起着决定性作用。近年来研究表明,心肌ＳＲ钙转运蛋白表达异常是多种心脏病的重要病理生理机制。目前已恨现多种参与ＳＲ钙转运蛋白表达调控的因素。     

阿霉素对兔心肌损伤与心肌ATP酶活性和NOS表达的关系

目的探讨阿霉素对心肌损伤与心肌ATP酶活性和NOS表达变化的关系.方法用治疗剂量阿霉素静脉注射建立兔阿霉素心肌损伤模型作为模型组静脉注射生理盐水作为对照组.取心肌组织进行HE染色及超薄切片染色;采用Padykula及Herman法和NADPH-d酶组织化学染色;进行图象分析数据进行统计学检验;观察和比较两组动物心肌组织中ATP酶和NOS的变化.结果病理学检查和电镜观察表明模型组心肌组织和超微结构受损伤;酶组织化学染色和图象分析显示Ca2+-ATP酶活性下降而NOS表达上调模型组与对照组相比 P＜0.01 具有显著性差异.结论治疗剂量阿霉素能够降低心肌组织中Ca2+-ATP酶的活性和上调NOS的表达并可能是导致心肌损伤的重要原因.