慢性阻塞性肺疾病大鼠主要脏器γ-GCS活性及其mRNA表达变化

目的:研究慢性阻塞性肺疾病(COPD)大鼠血浆、肺、心、肝、和肾组织中氧化/抗氧化水平,及γ谷氨酰半胱氨酸合成酶(γ-GCS)活性及其表达在各器官组织中的差异和变化。方法:健康雄性Wistar大鼠14只,随机分COPD模型组和对照组,每组7只。采用每日熏香烟和两次气管内滴入脂多糖(LPS)法制作COPD大鼠模型。检测大鼠血浆、肺、心、肝和肾组织中还原型谷胱甘肽(GSH)、活性氧(ROS)、总抗氧化力(T-AOC)和γ-GCS活性。用逆转录-聚合酶链反应(RT-PCR)法检测肺、心、肝和肾组织中γ-GCS mRNA的表达。结果:COPD组大鼠心、肝中GSH、ROS、T-AOC和γ-GCS活性均显著增高(P均<0.05),但未显示出明显氧化/抗氧化失衡。肺中GSH和ROS提高,而T-AOC下降明显(P均<0.05),表明提高的GSH不足以抵御氧化作用,明显存在氧化/抗氧化失衡。血清中ROS增高,GSH和T-AOC下降明显,显示系统性氧化/抗氧化失衡。COPD大鼠肺组织γ-GCS mRNA表达较对照组显著增高(P<0.05),而心、肝、肾组织中γ-GCS mRNA表达与对照组无明显差异(P>0.05)。结论:COPD大鼠肺内存在氧化/抗氧化失衡,肺组织是γ-GCS表达的主要部位,在抗氧化损伤中可能发挥重要作用。     

硫化氢体系在大鼠低氧性肺动脉平滑肌细胞增殖中的意义

目的　探讨低氧对肺动脉平滑肌细胞中胱硫醚 γ 裂解酶 (CSE)基因表达的影响和硫化氢对肺动脉平滑肌细胞增殖的调节作用。方法　人工培养大鼠的肺动脉平滑肌细胞 ,实验分为 1.对照组 ;2 .硫氢化钠 (NaHS)组 :10 - 4mol/LNaHS处理 2 4h ;3 .低氧组 :氧浓度 1%以下 2 4h ;4.低氧 NaHS组 :低氧 2 4h ,10 - 4mol/LNaHS。每组各 6孔细胞。用3H TdR掺入估计细胞增殖 ,用定量竞争性RT PCR方法测定CSEmRNA含量 ,评价CSE基因表达。结果　低氧组平滑肌细胞中的CSEmRNA含量较对照组减少 67% (P <0 .0 1)。低氧组细胞的3H TdR掺入较对照组增加 66% (P <0 .0 1) ;NaHS组细胞的3H TdR掺入较对照组减少 3 7%(P <0 .0 1) ;低氧 NaHS组的3H TdR掺入较低氧组减少 2 9% (P <0 .0 1)。结论　低氧使人工培养的大鼠肺动脉平滑肌细胞中CSE基因表达下调 ,硫化氢对大鼠肺动脉平滑肌细胞增殖有抑制作用。     

Skin fragility in the wild-derived,inbred mouse strain Mus pahari/EiJ

Mus pahari is a wild-derived, inbred mouse strain. M. pahari colony managers observed fragility of this strain's skin resulting in separation of tail skin from the mouse if handled incorrectly. Tail skin tension testing of M. pahari resulted in significantly lowered force threshold for caudal skin rupture and loss in comparison to closely related inbred mouse species and subspecies and even more than a model for junctional epidermolysis bullosa. Histologically, the tail skin separated at the subdermal level with the dermis firmly attached to the epidermis, excluding the epidermolysis bullosa complex of diseases. The dermal collagen bundles were abnormally thickened and branched. Elastin fiber deposition was focally altered in the dermis adjacent to the hair follicle. Collagens present in the skin could not be differentiated between the species in protein gels following digestion with pepsin. Together these data suggest that M. pahari have altered extracellular matrix development resulting in separation of the skin below the level of the dermis with moderate force similar to the African spiny mouse (Acomys spp.).     

吡喹酮对体外培养的斯氏肺吸虫的作用

斯氏肺吸虫童虫和成虫接触含吡喹酮10μg/ml和100μg/ml的培养基后强烈收缩,虫体活动减弱以致消失。成虫受药物作用后1h,扫描电镜下可见吸盘收缩,外皮肿胀,皮泡形成;透射电镜观察发现外皮胞质突起肿大,空泡形成及破溃,基质中分泌体减少。吡喹酮杀死斯氏肺吸虫的机制可能与挛缩虫体和损伤外皮超微结构,使其生理功能和物质代谢紊乱有关。     

The effect of opioids on inspiratory muscle fatigue during inspiratory resistive loading

Summary. The effect of opioids on inspiratory muscle function under high mechanical load is still unknown. Even less clear is the extent to which opioids influence the shift of the electromyographic power spectrum of the inspiratory muscles to lower frequencies during ventilatory stress. We studied seven healthy subjects breathing against high inspiratory threshold loads until exhaustion while keeping the minute ventilation constantly high. We compared runs with and without administration of 0.2 mg kg^-1 of morphine sulphate intramuscularly; two subjects were given 30 mg morphine sulphate so that we could study the effect of higher opioid concentration. The endurance time (T_lim), the diagraphragmatic electromyogram (EMG), the transdiaphragmatic pressures (Pdi) and the ventilatory effort sensation were analysed. Morphine did not have any effect on T_lim or on the effort sensation elicited by the inspiratory resistance in both concentrations. Analysing the spectral shifts of the diaphragmatic EMG, we did not find any significant difference in the decrease of the centroid frequency between drug and control runs. Furthermore, the activation pattern of the diaphragm and the intercostal muscles, evaluated from the percentage contribution of oesophageal and gastric pressures on the transdiaphragmatic pressure swings, did not change following the administration of morphine. Our study shows that morphine does not change the function of the inspiratory muscles during high-resistive breathing. Morphine does not affect the electromyographic power spectrum of the diaphragm during those resistive breathing runs, either. This points out that during stressful ventilatory situations, the shift of the electromyographic power spectrum is attributed to a peripheral (muscular) event consequent to muscle fatigue and not to the elaboration of endogenous opioids.     

Parry-Romberg综合征19例报道

目的 回顾分析Parry-Romberg综合征的临床特征、诊断要点，并探讨5种血管化游离组织瓣(腹股沟真皮脂肪瓣、大网膜瓣、背阔肌瓣、前锯肌瓣、背阔肌-前锯肌-蒂双瓣)行颜面萎缩畸形整复的临床价值。方法 对19例Parry—Romberg综合征患者进行回顾性研究．分析病程、发病部位，临床表现、游离组织瓣的选择、术后随访功能恢复情况．探讨不同组织瓣行颜面萎缩畸形充填整复的适应证和优缺点。本组病例中男性9例，女性l0例。年龄12-48岁，中位年龄23岁。右侧11例，左侧8例。病程4-16a，中位病程9a。病损涉及半侧颜面组织，如皮肤、皮下组织、肌、软骨及骨．造成部分或全部萎缩。结果 19例患者全部用游离组织瓣修复，其中腹股沟真皮脂肪瓣ll例，大网膜瓣4例，背阔肌瓣2例．前锯肌瓣1例，前锯肌瓣 背阔肌-蒂双瓣l例。所有组织瓣均经血管吻合，除l例腹股沟真皮脂肪瓣因术后感染发生部分坏死液化外，其余均全部成活(94．7％)，术后随访6个月-5a，除3例因局部臃肿等原因需行二期修复外．颜面凹陷畸形得到满意修复。结论 应用吻合血管的游离组织移植技术矫正Parry-Romberg综合征颜面萎缩畸形，恢复和重建颜面形态和丰满度，有着良好的效果。腹股沟真皮脂肪瓣具有供区隐蔽，组织供应量大，且其吸收有一定自限性等特点。最多用于这种畸形的填塞修复。前锯肌或联合背阔肌瓣，由于可以同期进行神经吻合的动力性修复，且血管蒂解剖恒定．值得推荐应用。而大网膜瓣由于需剖腹．患者易产生恐惧心理而拒绝,宜作二线选择。     

卡托普利及合用氯沙坦对大鼠心肌梗死区肌纤维细胞增殖和功能的影响

目的:比较卡托普利组和卡托普利与氯沙坦合用组急性心肌梗死(AMI)大鼠心肌瘢痕组织的肌纤维细胞在离体情况下的增殖率及转化生长因子-1(TGF-β1)水平。方法:雄性wistar大鼠36只,前降支结扎术后存活12h以上者随机分成对照组、卡托普利组和合用组,用药14d后分离培养梗死区肌纤维细胞。流式细胞技术检测血管紧张素Ⅱ(AngⅡ),刺激前后S期细胞比率(SPF)和增殖指数(PI),酶联免疫吸附实验(ELASA)法检测培养液中TGF-β1浓度。结果:AMI后梗死区肌纤维细胞具有极高的增殖活性。合用组SPF/PI低于对照组,而卡托普利组与对照组相比无统计学意义。合用组培养液中TGF-β1浓度低于对照组和卡托普利组。各组肌纤维细胞对AngⅡ刺激的反应性无统计学意义。结论:AMI后早期在有效剂量卡托普利的基础上加用氯沙坦更强抑制梗死区肌纤维细胞的增殖能力和生长因子产生。     

缺氧诱导因子-1α(HIF-1α)在动脉粥样硬化斑块中的表达及血管生成关系

目的:观察缺氧诱导因子-1α(HIF-1α)在动脉粥样硬化(As)斑块中的表达,探讨HIF-1α与斑块血管生成的关系。方法:24只Wistar大鼠随机分为正常组8只(普通饲料)和As模型组16只(高脂饮食+VitD3)。实验3个月后,检测血清总胆固醇(TC)、甘油三脂(TG);取主动脉石蜡包埋切片,HE染色;测量主动脉斑块占内膜总面积比(RAAPIs),内膜中膜面积比(I/M);免疫组化SP法检测HIF-1α蛋白的表达情况,鼠单克隆抗体CD34计数新生血管数目(MVD)。结果:实验后模型组血清TC、TG水平较正常组明显升高[(3.30±0.35)vs(1.51±0.19);(0.85±0.12)vs(0.50±0.14)],差异有统计学意义(P<0.01);模型组中RAAPIs,I/M明显高于正常组(P<0.05);模型组中HIF-1α蛋白表达增高;正常组中HIF-1α未见表达(87.5%vs 0%,P<0.01);模型组中微血管密度(MVD)明显高于正常组[(13.14±2.45)vs 0,P<0.05];不稳定斑块组HIF-1α、MVD均高于稳定斑块组[(100%vs 66.6%),(14.30±1.70)vs(10.25±1.26),P<0.05)],HIF-1α蛋白表达与MVD表达呈正相关(r=0.704,P=0.005)。结论:HIF-1α可通过促进As斑块内血管生成,从而增加斑块的不稳定性;HIF-1α的含量可能是影响斑块稳定性的重要因素。     

L和L/T型钙通道对急性梗死心肌肌腱蛋白的调节

目的:研究L和L/T型钙通道对梗死心肌基质金属蛋白酶(MMP-2、MMP-3、MMP-9)及细胞外间基质肌腱蛋白(tenascin-c,TN-C)的影响。方法:结扎大鼠左冠状动脉建立心肌梗死模型,术前7d分别用安慰剂、L型钙通道阻滞剂阿莫地平(4mg·kg-1.d-1)、L/T型钙通道阻滞剂米贝拉地尔(10mg·kg-1.d-1)。术后1d、3d、7d分别检测左心室游离壁(left ventricular free wall,LVFW)MMP-2、MMP-3及MMP-9蛋白表达;免疫荧光检测LVFW心肌TN-C的分布。结果:术前LVFW心肌排列基本正常,术后7dLVFW心肌有不同程度的坏死、肥厚及纤维化。术后1d、3d、7dLVFWMMP-2、MMP-3、MMP-9及TN-C蛋白表达一直处于高水平,各时相点与基础值相比差异有显著性(P<0.01)。米贝拉地尔更明显地抑制LVFWMMP-2、MMP-3、MMP-9及TN-C上调,缩小心肌梗死病灶,阿莫地平能抑制MMP-2、MMP-3、MMP-9及TN-C上调,但较米贝拉地尔弱。结论:心肌梗死病理过程中,梗死病灶内MMP-2、MMP-3、MMP-9及TN-C上调,L和L/T型钙通道阻滞剂能减轻心肌重构与选择性的抑制心肌组织中的MMP-2、MMP-3、MMP-9及TN-C表达有关。