淫羊藿苷缓解腹部皮瓣缺血再灌注损伤模型大鼠的作用及机制研究

摘要 目的：研究淫羊藿苷缓解腹部皮瓣缺血再灌注损伤（IRI）模型大鼠的作用及机制。方法：取30只SD级大鼠作为研究对象,将其按照随机数字表法分作假手术组、模型组以及淫羊藿苷组,每组各10只。其中模型组和淫羊藿苷组大鼠均制作大鼠腹部皮瓣IRI模型,假手术组以及模型组大鼠予以生理盐水腹腔注射,淫羊藿苷组大鼠则予以淫羊藿苷腹腔注射。对比各组大鼠皮瓣存活面积及存活率、血清炎症因子以及氧化应激指标水平、皮瓣组织中p38丝裂原活化蛋白激酶（p38 MAPK）信号通路相关蛋白表达情况。结果：模型组、淫羊藿苷组大鼠的皮瓣存活面积及存活率均低于假手术组,但淫羊藿苷组大鼠的皮瓣存活面积及存活率均高于模型组（P＜0.05）。模型组、淫羊藿苷组大鼠血清白细胞介素-10（IL-10）均低于假手术组,但淫羊藿苷组高于模型组;模型组、淫羊藿苷组大鼠血清肿瘤坏死因子-?琢（TNF-?琢）均高于假手术组,但淫羊藿苷组低于模型组（P＜0.05）。模型组、淫羊藿苷组大鼠血清超氧化物歧化酶（SOD）、谷胱甘肽（GSH）水平均低于假手术组,但淫羊藿苷组大鼠血清SOD、GSH水平均高于模型组;模型组、淫羊藿苷组大鼠血清丙二醛（MDA）水平均高于假手术组,但淫羊藿苷组大鼠血清MDA水平低于模型组（P＜0.05）。模型组、淫羊藿苷组大鼠皮瓣组织p38 MAPK、丝裂原活化蛋白激酶磷酸酶-2（MKP-2）相对表达量均高于假手术组,但淫羊藿苷组皮瓣组织p38 MAPK相对表达量低于模型组,而MKP-2相对表达量高于模型组（P＜0.05）。结论：淫羊藿苷可通过调控p38 MAPK信号通路缓解炎症反应及氧化应激,发挥减轻腹部皮瓣IRI的作用。     

姜黄素预处理对沙漠干热环境猪腹部枪弹伤模型生存时间的影响

目的:探讨姜黄素预处理对沙漠干热环境腹部枪弹伤动物模型生存时间的影响。方法:将24头长白仔猪随机分为2组(n=12):姜黄素预处理组和对照组。姜黄素预处理组给予长白仔猪姜黄素100 mg/kg拌料饲养,每天1次,连续7天,对照组给予常规饲料喂养。第8天,将两组猪放入西北特殊环境人工实验舱内,设置环境温度(40.5±0.5)℃,相对湿度(10±2)%,禁食水,放置3小时后建立腹部枪弹伤模型,模型成功后继续放在沙漠干热环境中,每10分钟检测体温变化,并计算长白仔猪的存活时间。结果:姜黄素预处理组平均存活时间为(85.27±2.39)min,对照组的动物模型平均生存时间为(60.10±3.25)min,姜黄素预处理组的生存时间平均比对照组延长约25 min,两组的Kaplan-Meier生存曲线经Log Rank检验具有显著性差异(P0.01)。建立腹部枪弹伤模型后,在相应时间点,姜黄素预处理组的体温明显低于未处理组(P0.01),姜黄素预处理组70 min时的体温与对照组50 min体温比较差异无统计学意义(P0.05)。结论:姜黄素预处理可明显提高干热环境下猪腹部枪弹伤模型的生存时间,体温升高可能是反映干热环境腹部枪弹伤后病程进展的重要指标。     

Enhanced Phosphodiestric Breakdown of Phosphatidylinositol Bisphosphate After Experimental Brain Injury

Abstract: Regional levels of lactate and inositol 1,4,5-trisphosphate (IP₃), a cellular second messenger of the excitatory neurotransmitter system, were measured after lateral fluid percussion (FP) brain injury in rats. At 5 min postinjury, tissue lactate concentrations were significantly elevated in the cortices and hippocampi of both the ipsilateral and contralateral hemispheres. By 20 min postinjury, lactate concentrations were elevated only in the cortices and hippocampus of the ipsilateral hemisphere. Whereas the IP₃ concentrations were elevated in the hippocampi of the ipsilateral and contralateral hemisphere and in the cortex of ipsilateral hemisphere at 5 min postinjury, no elevation in these sites was found at 20 min postinjury. Histologic analysis revealed neuronal damage in the cortex and CA3 regions of hippocampus ipsilateral to the injury at 24 h postinjury. The present results suggest activation of the phosphoinositide signal transduction pathway at the onset of injury and of a possible requirement of early persistent metabolic dysfunction (>20 min) such as the lactate accumulation in the delayed neuronal damage.     

BI1 alleviates cardiac microvascular ischemia-reperfusion injury via modifying mitochondrial fission and inhibiting XO/ROS/F-actin pathways

Pathogenesis of cardiac microvascular ischemia-reperfusion (IR) injury is associated with excessive mitochondrial fission. However, the upstream mediator of mitochondrial fission remains obscure. Bax inhibitor 1 (BI1) is linked to multiple mitochondrial functions, and there have been no studies investigating the contribution of BI1 on mitochondrial fission in the setting of cardiac microvascular IR injury. This study was undertaken to establish the action of BI1 on the cardiac microvascular reperfusion injury and figure out whether BI1 sustained endothelial viability via inhibiting mitochondrial fission. Our observation indicated that BI1 was downregulated in reperfused hearts and overexpression of BI1 attenuated microvascular IR injury. Mechanistically, reperfusion injury elevated the levels of xanthine oxidase (XO), an effect that was followed by increased reactive oxygen species (ROS) production. Subsequently, oxidative stress mediated F-actin depolymerization and the latter promoted mitochondrial fission. Aberrant fission caused mitochondrial dysfunction and ultimately activated mitochondrial apoptosis in cardiac microvascular endothelial cells. By comparison, BI1 overexpression repressed XO expression and thus neutralized ROS, interrupting F-actin-mediated mitochondrial fission. The inhibitory effect of BI1 on mitochondrial fission sustained endothelial viability, reversed endothelial barrier integrity, attenuated the microvascular inflammation response, and maintained microcirculation patency. Altogether, we conclude that BI1 is essential in maintaining mitochondrial homeostasis and alleviating cardiac microvascular IR injury. Deregulated BI1 via the XO/ROS/F-actin pathways plays a causative role in the development of cardiac microvascular reperfusion injury.     

Transcriptional landscape of alternative splicing during peripheral nerve injury

Alternative splicing (AS) regulates a variety of biological activities in numerous tissues and organs, including the nervous system. However, the existence and specific roles of AS events during peripheral nerve repair and regeneration remain largely undetermined. In the current study, by mapping splice-crossing sequence reads, we identified AS events and relevant spliced genes in rat sciatic nerve stumps following sciatic nerve crush. AS-related genes at 1, 4, 7, and 14 days post nerve crush were compared with those at 0 day to discover alternatively spliced genes induced by sciatic nerve crush. These injury-induced alternatively spliced genes were then categorized to diseases and biological functions, genetic networks, and canonical signaling pathways. Bioinformatic analysis indicated that these alternatively spliced genes were mainly correlated to immune response, cellular growth, and cellular function maintenance. Our study elucidated AS events following peripheral nerve injury and might help deepen our understanding of the molecular mechanisms underlying peripheral nerve regeneration.     

带鱼下脚料水解物对大鼠血管内皮损伤的影响

通过检测带鱼下脚料蛋白酶水解物的药理作用,为带鱼下脚料的开发利用提供理论依据。用带鱼下脚料三酶混合水解物喂养盐酸肾上腺素造成血管内皮损伤模型的大鼠,检测大鼠血清中血管内皮生长因子(VEGF)和血管性血友病因子(vWF)的含量变化。结果表明:实验不给药组与空白对照组及实验给药组相比,VEGF和vWF的含量存在显著差异。注射盐酸肾上腺素成功制造了血管内皮损伤模型,带鱼下脚料蛋白酶水解物对内皮损伤没有显著影响,但对损伤后的内皮修复有明显的促进作用。     

外周损伤引起成年大鼠体感皮层的功能重组

为了了解外周神经损伤对体感皮层分域组构的影响,在成年大鼠上观察了切断坐骨神经(SC)前、即刻和切断后数周内后爪皮层代表区的改变。在盐酸氯胺酮麻醉下,用微电极记录后爪皮肤轻触刺激在对侧体感皮层工区诱发的多单位反应,得出后爪的皮层代表区图。在16例中,8例大鼠观察了切断SC的即时效应。结果表明,不但SC代表区丧失皮肤反应性,原隐神经(SA)代表区的皮肤反应性也明显下降或消失,同时神经元自发活动也明显减弱。另8例大鼠在切断后数周内做了1～3次重复测定。在最初几天,原SA代表区范围内多数记录点的皮肤反应性仍未恢复,但在原SC代表区内,一些记录点转而对SA皮肤轻触刺激起反应。在随后数周内SA代表区进行性地扩张,占领了大部分原SC代表区。这一结果说明成年大鼠外周神经损伤可导致体感皮层发生显著的重组改变。     

Seasonal patterns of dehydrins and 70-kDa heat-shock proteins in bark tissues of eight species of woody plants

Although considerable effort has been directed at identifying and understanding the function and regulation of stress-induced proteins in herbaceous plants, reports concerning woody plants are limited. Studies with herbaceous crops have revealed similarities in the types of proteins that accumulate in response to a wide array of abiotic stresses and hormonal cues such as the accumulation of abscisic acid. Many of the identified proteins appear to be related to dehydrins (the D-11 subgroup of late-embryogenesis-abundant proteins). The objective of the present study was to determine if seasonal induction of dehydrins is a common feature in woody plants and to see if seasonal patterns existed for other stress-induced proteins. Bark tissues from eight species of woody plants were collected monthly for a period of 1.5 years. The species included: peach (Prunus persica) cv. Loring; apple (Malus domestica) cv. Golden Delicious; thornless blackberry (Rubus sp.) cv. Chester; hybrid poplar (Populus nigra); weeping willow (Salix babylonica); flowering dogwood (Cornus florida); sassafras (Sassafras albidum); and black locust (Robinia pseudo-acacia). Immunoblots of bark proteins were probed with a polyclonal antibody recognizing a conserved region of dehydrin proteins, and monoclonal antibodies directed against members of the HS70 family of heat-shock proteins. Some proteins, immunologically related to dehydrins, appeared to be constitutive; however, distinct seasonal patterns associated with winter acclimation were also observed in all species. The molecular masses of these proteins varied widely, although similarities were observed in related species (willow and poplar). Identification of proteins using the monoclonal antibodies (HSP70, HSC70, BiP) was more definitive because of their inherent specificity, but seasonal patterns were more variable among the eight species examined. This study represents only a precursory examination of several proteins reported to be stress related in herbaceous plants, but the results indicate that these proteins are also common to woody plants and that further research to characterize their regulation and function in relation to stress adaptation and the perennial life cycle of woody plants is warranted.