乌司他丁保护百草枯中毒大鼠肺免受损伤的作用

目的:探讨乌司他丁保护百草枯中毒大鼠肺免受损伤的作用及其机制。方法:Wistar大鼠108只,随机分为对照组、百草枯组和乌司他丁组。百草枯组和乌司他丁组给予百草枯灌胃染毒,对照组给予无菌生理盐水灌胃,乌司他丁组同时给予乌司他丁治疗。1、3、7、14、21、28 d测血清中的MDA、SOD、IL-6、IL-10和TNF-α水平,以及肺组织中的p38 MAPK、MMP-2和TIMP-1表达水平。结果:1、3、7 d百草枯组和乌司他丁组的SOD均较对照组下降(P0.01),乌司他丁组SOD明显高于百草枯组(P0.05)。1、3、7 d百草枯组和乌司他丁组的MDA、IL-6、IL-10及TNF-α均较对照组增高(P0.01),乌司他丁组各指标明显低于百草枯组(P0.05)。1、3、7、14、21、28d百草枯组和乌司他丁组肺组织中的p38 MAPK及TIMP-1均较对照组增高(P0.01),乌司他丁组各指标明显低于百草枯组(P0.05)。1、3、7、14、21 d百草枯组和乌司他丁组肺组织中的MMP-2均较对照组增高(P0.01),乌司他丁组MMP-2明显低于百草枯组(P0.05)。结论:乌司他丁通过抑制p38 MAPK信号通路及抗炎、抗氧化作用保护百草枯中毒大鼠肺免受损伤的作用。     

亚硒酸钠对UVB损伤人角质形成细胞的保护作用

目的:研究亚硒酸钠(Na2Se O3)对中波紫外线(UVB)损伤人角质形成细胞的保护作用。方法:培养永生化人角质形成细胞(Ha Ca T细胞),实验分为4组处理:(1)正常对照组;(2)Na2Se O3组:分别加入1 nmol/L、10 nmol/L、50 nmol/L、100 nmol/L、200 nmol/L和1μmol/L的Na2Se O3预孵育24 h;(3)UVB组:300、600和900 J/m2UVB照射;(4)Na2Se O3+UVB组:Na2Se O3预孵育24 h后进行UVB照射。采用MTT法检测细胞增殖活性,采用流式细胞仪检测300 J/m2UVB照射后细胞的凋亡率。结果:(1)UVB组与正常对照组比较,细胞增殖活性显著降低(P0.05),细胞活性与UVB照射剂量呈负相关;(2)Na2Se O3组与正常对照组比较,细胞增殖活性无明显差异;(3)不同浓度Na2Se O3+UVB组与UVB组比较,细胞增殖活性增加,差异显著(P0.05),其中100 nmol/L组促进细胞增殖作用最强;(4)300 J/m2UVB照射后,不同浓度Na2Se O3+UVB组与UVB组比较,凋亡率下降,差异显著(P0.05),其中100 nmol/L组抑制凋亡作用最强。结论:UVB对角质形成细胞有损伤作用,且与照射剂量呈正相关;Na2Se O3具有光保护性能,可减轻UVB辐射损伤人角质形成细胞。     

miR-21反义寡核苷酸增强地西他滨体外抗白血病效应

目的:研究miR-21反义寡核苷酸(anti-miR-21 oligonucleotide,AMO)对地西他滨(decitabine,DCA)抗白血病效应的影响及可能机制。方法:将AMO和无义寡核苷酸(scramble oligonucleotide,SCR)通过脂质体转染导入HL-60细胞,实时荧光定量PCR(real-time PCR)验证转染效率,再分别与DCA 0.5、2.0和4.0μmol/L作用48 h。Real-time PCR分别检测人周期节律蛋白3(h Per3)mRNA表达,Annexin V/PI法检测凋亡,流式细胞术检测CD117和CD11b平均荧光强度(MFI)。结果:AMO转染组miR-21表达(0.35±0.07)低于空白组(0.71±0.07)和SCR转染组(0.66±0.05),差异有统计学意义(P0.05)。AMO转染组的HL-60细胞DCA的IC50低于空白组和SCR转染组(P0.01)。同一浓度下,AMO组的早期凋亡率、CD11b的MFI和h Per3 mRNA均高于同一浓度药物作用的空白组和SCR组,CD117 MFI均低于同一浓度药物作用的空白组和SCR组,差异均具有统计学意义(P0.01)。结论:AMO能显著促进DCA体外抗白血病效应,其机制可能与其协助激活h Per3的表达有关。     

Ac-SDKP经HSP27调节锌指蛋白而抑制肺上皮细胞-间质转化

目的:探讨N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸(Ac-SDKP)是否通过抑制热休克蛋白27(heat-shock protein 27,HSP 27)的表达,进而抑制锌指蛋白SNAI1、SNAI2的表达,而发挥阻抑转化生长因子(TGF)-β1诱导的人肺泡Ⅱ型上皮细胞向间质细胞(肌成纤维细胞)的转化以及Ⅰ型、Ⅲ型胶原蛋白的表达。方法:激光共聚焦检测TGF-β1诱导的人肺泡Ⅱ型上皮细胞向肌成纤维细胞转化中HSP27及SNAI1、SNAI2蛋白的共定位表达;real-time PCR法检测HSP27、SNAI1和SNAI2 mRNA的表达;Western blotting法检测HSP27、SNAI1、SNAI2和Ⅰ型、Ⅲ型胶原蛋白的表达,以及转染HSP27干扰质粒后SNAI1、SNAI2蛋白及Ⅰ型、Ⅲ型胶原蛋白表达的变化。结果:与对照组相比,TGF-β1刺激组HSP27、SNAI1、SNAI2及Ⅰ型、Ⅲ型胶原蛋白表达增强;给予Ac-SDKP干预后,HSP27、SNAI1、SNAI2及Ⅰ型、Ⅲ型胶原蛋白表达明显降低,差异有统计学意义。用HSP27的干扰质粒转扰细胞后,SNAI1、SNAI2及Ⅰ型、Ⅲ型胶原蛋白表达降低,其中SNAI1和Ⅰ型、Ⅲ型胶原蛋白的表达与TGF-β1刺激组比较差异有统计学意义。这与Ac-SDKP干预的结果相似。结论:Ac-SDKP能够通过对HSP27表达的调节,降低锌指蛋白SNAI1和SNAI2的表达,进而抑制肺泡Ⅱ型上皮细胞向肌成纤维细胞的转化及胶原蛋白的合成。     

临产后子宫体部平滑肌高表达HSP27和αB-crystallin

 ［摘要］目的:研究临产前后子宫体部平滑肌热休克蛋白27（HSP27）和α-晶体蛋白B链（αB-crystallin）的表达变化,探讨其在临产后子宫平滑肌收缩中的可能作用。方法:采用比较蛋白质组学技术鉴定出足月未临产和自然临产人子宫体部平滑肌中HSP27和αB-crystallin蛋白存在差异性表达,应用RT-PCR、免疫组化和免疫印迹方法对临产前后子宫体部平滑肌中HSP27蛋白的表达进行验证。结果:临产后子宫体部平滑肌高表达HSP27和αB-crystallin（P<0.05）。足月未临产和临产人子宫体部平滑肌双向凝胶电泳图谱均存在4个分子量相等、等电点不同的HSP27蛋白斑点,ImageMaster 2D Platinum 软件分析仅有1个HSP27蛋白斑点具有显著差异（P<0.05）,余3个HSP27蛋白斑点无显著差异（P>0.05）。RT-PCR、免疫组化和免疫印迹对HSP27蛋白验证结果与蛋白质组学一致。结论: HSP27和αB-crystallin蛋白在临产后人子宫体部平滑肌高表达,提示这2个小分子热休克蛋白可能参与了临产后子宫体部平滑肌细胞的收缩事件。     

PULMONARY FUNCTION STUDIES IN LONG-TERM SURVIVORS WITH ARTIFICIAL VENTILATION IN THE NEONATAL PERIOD

Abstract. Borkenstein, J., Borkenstein, M. and Rosegger, H. (Department of Medicine and Department of Paediatrics, University of Graz, Landeskrankenhaus, Graz, Austria). Pulmonary function studies in long-term survivors with artificial ventilation in the neonatal period. Acta Paediatr Scand, 69: 159, 1980.—Lung function tests in 11 children aged 2.5–5.5 years who required intermittent positive pressure ventilation (1–624 hrs) in infancy were obtained. The conditions necessitating artificial ventilation were hyaline membrane disease, neonatal apneic spells, aspiration of milk, and birth asphyxia. On examination the probands were in a good healthy state and without any subjective signs of dyspnea. Lung volumes could be measured in all of the probands. They did not show any statistically significant deviation from standards for height and correlated with the age of the probands. Time related flow rates were sufficiently measurable in 7 probands only, who cooperated adequately. In 6 of them the expiratory flow showed a decrease of the effort independent portion with a slight increase in the total airway resistance. There was no correlation between the condition requiring artificial ventilation, the former therapeutic characteristics and the degree of the pathological lung function tests. The results of this investigation suggest damage of the smallest airways which could be the reason for the obstructively impaired expiratory patterns seen in 6 of the probands.     

IRON RELEASE FROM THE STORES: A MECHANISM IN MAINTENANCE OF CONCENTRATION OF HEMOGLOBIN IN LOW-BIRTH-WEIGHT INFANTS

Abstract. Lundström, U. (Pediatric Hematology, Children's Hospital, University of Helsinki, Findland). Iron release from the stores: A mechanism in maintenance of concentration of hemoglobin in low-birth-weight infants. Acta Paediatr Scand, 69: 249, 1980.—After the resuming of the postnatal red cell production at two months of age infants are dependant on storage iron due to the great need for iron at a time when the iron content of the diet is low. This is even further accentuated in low-birth-weight infants. In this study the release of storage iron in the hemoglobin pool. During the two month period from two to four months of age at least 20 mg of iron per month was transferred from the storage sites for hemoglobin production. This amount represents 5 mg per kg of body weight and exceeds the rate iron was mobilized from storage sites in an adult male under experimental conditions. Rapid weight gain was associated with early depletion of iron stores. However, residual iron stores in infants with the slowest growth rate could not maintain the level of hemoglobin achieved in iron-supplemented low-birth-weight infants. These findings suggest that in rapidly growing low-birth-weight infants the need of iron for erythropoiesis is so great that iron deficient erythropoiesis may develop in the presence of iron stores if the diet is not supplemented with iron.     

B-lymphoproliferative disorders: a proposed unified pathogenetic pathway

The clinical features of lymphoproliferative diseases associated with paraproteinemia are briefly reviewed and correlated with current immunologic concepts in an effort to clarify the pathophysiology of B-lymphocyte disorders. B-lymphocyte maturation proceeds in a predictable manner from the Pre-B cell to the formation of idiotype specific plasma cells and memory B-lymphocytes. The immunoglobulin isotype produced by the mature plasma cell is determined by a site specific process of gene switching which proceeds from mu to alpha production. Lymphoproliferative diseases are the result of disordered B cell maturation and their clinical features can be explained by identifying the locus of the maturational defect.     

EVALUATION OF MECHANICAL VENTILATION IN NEWBORN INFANTS: I. Techniques and survival rates

Abstract. Lindroth, M., Svenningsen, N. W., Ahlström, H. and Jonson, B. (Neonatal Unit, Department of Paediatrics, University Hospital, Lund, Sweden). Evaluation of mechanical ventilation in newborn infants. 1. Techniques and survival rates. Acta Paediatr Scand, 69: 143, 1980.—The short-term outcome with survival rate, causes of death and neonatal complications in a 6-year material comprising 253 infants treated with intermittent positive pressure ventilation (IPPV) in the neonatal period has been analyzed in relation to different primary disorders necessitating IPPV treatment. The total survival rate was 53%. For the different diagnoses the survival rates were: hyaline membrane disease (HMD) 41%, apnoea repetens of immaturity 85%, severe birth asphyxia 46% and septicemia 59%. The total rate of pneumothorax during IPPV was 15% but occurred more often in the HMD group (28%). Trends in survival rates over the study period are discussed as are measurements for improvements.     

PLASMA SECRETIN IN NEONATES

Abstract. Lucas, A., Adrian, T. E., Bloom, S. R. and Aynsley-Green, A. (University Department of Paediatrics, John Radcliffe Hospital, Oxford and Hammersmith Hospital, London). Plasma secretin in neonates. Acta Paediatr Scand, 69: 205, 1980.—Plasma secretin has been measured in 96 normal 6-day-old term infants and in 158 healthy preterm infants whose mean post-partum ages were 2½, 6, 13 or 24-days. At birth, plasma secretin levels in both term and preterm infants were high compared with those seen in healthy fasting adults ( p > 0.001), but subsequently declined towards adult values. In contrast, preterm infants who had not been fed for the first 6 days of life, had presistently high basal plasma secretin values. In term infants at 6 days of age and in preterm infants up to 13 days, there was no se-cretin response to a feed. However, by 24 days, preterm infants showed a marked post-prandial secretin elevation ( p > 0.02). No correlations were found between plasma secretin concentrations and either blood glucose or plasma insulin concentrations following a feed. Significant adjustments in plasma secretin levels occur in the early weeks of life which may be influenced by enteral feeding.