基于中西医临床病症特点血栓闭塞性脉管炎动物模型分析

基于血栓闭塞性脉管炎的临床病症特点,通过查阅相关文献,整理分析并建立血栓闭塞性脉管炎的西医诊断标准与中医辨证标准,总结血栓闭塞性脉管炎动物模型的造模方法、造模对象、模型优缺点。分析其与中西医临床病症特点的吻合度,总结发现血栓闭塞性脉管炎动物模型与西医临床病症吻合度较高,与中医寒湿阻络证和热毒伤阴证吻合度较高,与湿热毒盛证和气血两虚证吻合度较低,没有与血脉淤阻证相吻合的动物模型。患肢病变程度、病理、血液流变学指标(血液黏度、红细胞沉降率)为最常检测指标。现阶段相对于大量临床治疗血栓闭塞性脉管炎的病例报道,实验研究相对薄弱,建立合理的模型判断量化标准,复制与中医证候吻合度更高的动物模型是日后的研究重点。     

基于临床病症特点的慢性脑缺血动物模型分析

慢性脑缺血是临床常见病、多发病,也是血管性痴呆、阿尔茨海默病等多种神经系统疾病共同的病理基础。本文基于慢性脑缺血的中西医临床病症特点,对现有的慢性脑缺血动物模型进行归纳与总结,并对动物模型与临床病症特点的吻合度具体评价,分析其优缺点及应用前景。目前关于慢性脑缺血模型建模方法主要有血管闭塞法、动静脉瘘及控制血管直径法,其中属血管闭塞法中的双侧颈总动脉结扎模型是慢性脑缺血最常用的模型。由于每一种模型均存在一定的优势和局限性,因此构建一种理想的慢性脑缺血动物模型,对于本病的病理机制研究和临床治疗及其并发症的防治均具有重大意义。     

人正常子宫颈移行上皮重症联合免疫缺陷小鼠模型的建立

目的探讨人正常子宫颈移行上皮重症联合免疫缺陷小鼠(SCID鼠)模型建立的可行性及其生物学特性。方法获取正常子宫颈组织的移行带标本,接种于12只SCID鼠皮下,随机分成3组,分别在2、4、6周取出其皮下移植物行HE染色、免疫组化及人乳头瘤病毒(HPV)DNA的检测。结果所有小鼠的移植物均存活,病理证实存在宫颈鳞柱状上皮并具有基底膜结构,上皮细胞免疫组织化学染色ki-67阳性,HPV DNA检测为阴性。结论初步建立了人正常子宫颈移行上皮SCID鼠模型,为进一步研究子宫颈上皮HPV感染致癌变过程提供了理想的动物模型。     

导泻排毒液清除化道毒物治疗急性中毒的实验研究

目的：探讨导泻排毒液通过清除消化道残留毒物而治疗急性中毒的机制。方法：观察导泻排毒液对小白鼠胃排空的影响;对小鼠白鼠肠功能的;对家兔离体肠平滑肌的影响。对大白鼠口服苯巴比妥血药浓度的影响。结果：导泻降低小白鼠胃中甲基残留率,有促进胃排空作用,能提高小白鼠肠道炎末推进率,有增强肠道推进功能作用。能使家兔离体肠客收缩幅度增大,蠕皮明显加深,肠管肌张力明显增加,能降低大白鼠口服苯巴比妥血药浓度。与对照组     

The Effect of Insulin on the Intracellular Distribution of 14(R,S)-[18F]Fluoro-6-thia-heptadecanoic Acid in Rats

Purpose The aim of this study was to determine the effect of hyperinsulinemia on myocardial and hepatic distribution and metabolism of 14(R,S)-[¹⁸F]fluoro-6-thia-heptadecanoic acid ([¹⁸F]FTHA).Procedures Mitochondrial retention and intracellular lipid incorporation of [¹⁸F]FTHA were compared to that of [¹⁴C]-2-bromopalmitate or [¹⁴C]palmitate during hyperinsulinemic clamp vs. saline infusion in male Wistar rats.Results Mitochondrial ¹⁸F activity was increased in the heart (1.7 ± 0.4 vs. 0.5 ± 0.1% ID/g, P < 0.05), whereas it was reduced in the liver (1.1 ± 0.3 vs. 1.8 ± 0.4% ID/g, P < 0.05) during insulin vs. saline infusion, respectively. Mitochondrial [¹⁴C]-2-bromopalmitate activity was affected by insulin in a similar way in both tissues. The fractional esterification of [¹⁸F]FTHA into triglycerides was impaired compared to [¹⁴C]palmitate in both tissues, and [¹⁸F]FTHA was insensitive to the shift of esterification of fatty acids into complex lipids in response to insulin.Conclusions [¹⁸F]FTHA is sensitive to insulin-induced modifications of free fatty acid oxidative metabolism in rats but is insensitive to changes in nonoxidative fatty acid metabolism.     

Neonatal exposure to MK‐801 reduces mRNA expression of mGlu3 receptors in the medial prefrontal cortex of adolescent rats

Schizophrenia is considered as a “neurodegenerative” and “neurodevelopmental” disorder, the pathophysiology of which may include hypofunction of the N‐methyl‐d ‐aspartate receptor (NMDA‐R) or subsequent pathways. Accordingly, administration of NMDA‐R antagonists to rodents during the perinatal period may emulate some core pathophysiological aspects of schizophrenia. The effect of 4‐day (postnatal day; PD 7–10) administration of MK‐801, a selective NMDA‐R antagonist, on gene expression in the medial prefrontal cortex (mPFC), hippocampus, and amygdala was evaluated using quantitative polymerase chain reaction methods. Specifically, we sought to determine whether genes related to Glu transmissions, for example those encoding for NMDA‐Rs, metabotropic Glu receptors (mGluRs), or Glu transporters, were altered by neonatal treatment with MK‐801. Model rats showed downregulation of the mGluR3 subtype in the mPFC around puberty, especially at PD 35 in response to MK‐801 or during ontogenesis without pharmacological manipulations. Genes encoding for other mGluRs subtypes, that is NMDA‐Rs and Glu transporters, were not affected by the neonatal insult. These results suggest that NMDA‐R antagonism in the early course of development modulates the expression of mGluR3 in mPFC around puberty. Thus, mGluR3 may serve as a potential target to prevent the onset and progression of schizophrenia. Synapse 68:202–208, 2014 . © 2014 Wiley Periodicals, Inc.     

Recombinant tissue plasminogen activator enhances microglial cell recruitment after stroke in mice

The effect of recombinant human tissue plasminogen activator (rtPA) on neuroinflammation after stroke remains largely unknown. Here, we tested the effect of rtPA on expression of cellular adhesion molecules, chemokines, and cytokines, and compared those with levels of inflammatory cell recruitment, brain injury, and mortality over 3 days after transient middle cerebral artery occlusion (MCAO) in mice. Mortality was dramatically increased after rtPA treatment compared with saline treatment during the first day of reperfusion. Among the animals that survived, rtPA significantly increased CCL3 expression, microglia recruitment, and cerebral infarction 6 hours after MCAO. In contrast, the extent of neutrophils and macrophages infiltration in the brain was similar in both saline- and rtPA-treated animals. Recombinant human tissue plasminogen activator induced Il1b and Tnf expression, 6 and 72 hours after MCAO, respectively, and dramatically reduced interleukin 6 (IL-6) level 24 hours after reperfusion. A dose response study confirmed the effect of rtPA on CCL3 and Il1b expressions. The effect was similar at the doses of 1 and 10 mg/kg. In conclusion, we report for the first time that rtPA amplified microglia recruitment early after stroke in association with a rapid CCL3 production. This early response may take part in the higher susceptibility of rtPA-treated animals to reperfusion injury.