Necrostatin-1对雨蛙肽诱导的小鼠急性胰腺炎的保护作用

目的观察Necrostatin-1(Nec-1)对雨蛙肽诱导的小鼠急性胰腺炎(AP)的影响。方法 C57BL/6小鼠予以50μg/kg的雨蛙肽腹腔注射7次,间隔1 h,建立AP模型。于第1次雨蛙肽注射后3 h、6 h、9 h和12 h,取出胰腺组织,HE染色。Western blot检测RIP1和RIP3蛋白的表达;C57BL/6小鼠随机分为:Control组、Vehicle组、Nec-1组和Nec-1i组,予以50μg/kg的雨蛙肽腹腔注射10次,间隔1 h,第1次雨蛙肽注射2 h前,腹腔注射Nec-1(1 mg/kg,每6 h 1次)、Nec-1i或等体积溶剂和空白对照。于第1次雨蛙肽注射后12 h、18 h和24 h,收集血清和胰腺组织。检测血清淀粉酶和脂肪酶。HE染色评估胰腺损伤程度。Real-time RT-PCR检测胰腺组织IL-1β和TNF-αmRNA的表达。结果 RIP1和RIP3蛋白在雨蛙肽诱导的AP中逐渐升高,且与胰腺腺泡细胞的坏死呈正相关;应用Nec-1后,与Vehicle组和Nec-1i组比较,于12 h、18 h和24 h,小鼠血清淀粉酶和脂肪酶水平明显降低,胰腺组织病理评分也明显减少,同时胰腺组织中IL-1β和TNF-αmRNA的水平也明显降低。结论 Nec-1对实验性胰腺炎具有明显的保护作用;程序性坏死可能促进了急性胰腺炎的损伤。     

大麻素受体-1对内毒素诱导的大鼠小肠肌电活动的影响

目的研究不同浓度脂多糖（lipopolysaccharides,LPS）对大鼠小肠肌电活动的影响及大麻素1受体（CB1受体）激动剂HU210和拮抗剂AM251对这些影响的干预作用,以探讨LPS影响肠道运动的可能的机制。方法将48只SD雄性大鼠分为3大组8小组（每小组6只）：LPS处理组（包括LPS低浓度组、LPS高浓度组）,CB1受体激动剂干预组（包括HU210组、LPS低浓度＋HU210组、LPS高浓度＋HU210组）,CB1受体拮抗剂干预组（包括AM251组、LPS低浓度＋AM251组、LPS高浓度＋AM251组）。分别经腹腔注射各种相应药物,用Power Lab八道生理记录仪记录大鼠小肠平滑肌峰电活动的频率及振幅等,观察腹腔注射LPS、大麻素受体激动剂及拮抗剂后这些指标的变化。结果腹腔注射不同浓度LPS后,大鼠小肠平滑肌峰电频率和振幅均有明显降低（P〈0.05）;注射HU210后,大鼠小肠平滑肌峰电频率和幅度也均明显降低（P〈0.05）;而注射AM251后,大鼠小肠平滑肌峰电频率及幅度明显增加（P〈0.05）;腹腔注射不同浓度LPS和HU210,分别与LPS单独注射的比较,小肠平滑肌峰电频率更为降低,注射后30-60 min之间降低最为显著（P〈0.05）;腹腔注射不同浓度LPS和AM251,分别与LPS单独注射比较,肠平滑肌峰电频率升高,AM251逆转LPS的效应主要在注射后的30 min内,尤其对放电频率的逆转作用明显（P〈0.05）。结论腹腔注射LPS有降低大鼠小肠平滑肌电峰电频率和振幅的作用,且有浓度依赖性;CB1受体激动剂和拮抗剂对LPS诱导的大鼠小肠平滑肌峰电活动变化均有不同程度的影响,揭示CB1受体存在于大鼠体内,并参与内毒素血症时肠道运动紊乱的调节。     

慢性充血性心力衰竭患者QT离散度的临床意义

目的 观察QT离散度（QTd）在慢性充血性心力衰竭（CHF）患者中对猝死的预测。方法 收集近2年诊断明确的CHF病人62例作为观察对象,并选择47例正常人为对照,由专人测定患者入院时的首次常规心电图QT间期,测量导联每份心电图不少于7个。结果 CHF病人的QTd和QTd均明显大于正常人（P＜0．05）。结论 QTd可作CHF病人猝死的简单、实用的预测指标之一。     

非可控性炎症和肿瘤细胞上皮间质转化关系的研究进展

目的:总结国内外关于非可控性炎症和肿瘤细胞上皮间质转化关系的研究进展,探讨非可控性炎症在肿瘤细胞恶性转化中的作用及可能机制。方法:应用PubMed及CNKI期刊全文数据库系统,以"上皮间质转化(Epithelial-mesenchymaltransition,EMT)、非可控性炎症及肿瘤微环境"为关键词,检索2005-01-2010-12的相关文献。纳入标准:1)非可控性炎症与肿瘤的联系;2)EMT与肿瘤的关系;3)非可控性炎症对EMT的调控机制。根据纳入标准分析26篇文献。结果:在非可控性炎症状态下,TGF-β、TNF-α和ILs等细胞因子可通过NF-κB等信号通路,激活EMT相关转录因子,启动并维持肿瘤细胞EMT过程,增强肿瘤细胞的侵袭性和转移性;肿瘤细胞发生EMT后又可进一步促进肿瘤微环境的形成,以维持炎症的非可控性状态。结论:非可控性炎症与EMT之间关系十分密切,通过靶向抑制非可控性炎症-EMT信号网络中的关键节点以阻断EMT过程,有望为肿瘤防治提供新的途径。     

感染性胰腺坏死的治疗进展

急性胰腺炎是一种内科常见急症,胰腺坏死并发感染可导致严重脓毒血症甚至多器官功能衰竭。近年来,随着消化内外科微创手术水平的快速提高,微创升阶梯理念已逐渐代替外科清创,成为胰腺感染性坏死（infected pancreatic necrosis, IPN）的首选治疗策略。本文对超声内镜下穿刺引流-内镜下经腔坏死切除术-LAMS支架置入+鼻胆管引流的消化内镜下升阶梯治疗策略的有效性、安全性以及内镜下操作细节等作一详细综述,对内镜升阶梯治疗与外科微创升阶梯治疗策略的各自优势进行阐述,为IPN临床治疗策略的选择提供理论指导。     

No spatial memory deficit exists in Kunming mice that recently recovered from motor defects following 3-nitropropionic acid intoxication

Objective

Numerous studies have described both motor defects and cognitive impairments in several strains of rodents following 3-nitropropionic acid (3-NP) intoxication. In the present study, we investigated spatial recognition memory in Kunming mice that just recovered from motor defects induced by 3-NP.

Methods

Mouse model was made by systemic subacute 3-NP treatment, and spatial recognition memory was measured through the Y-maze Test, a simple two-trial recognition test.

Results

(1) On day 15 following 3-NP treatment, affected Kunming mice did not show motor defects in the Rotarod test and presented normal gait again. (2) In the following Y-maze test after 1h interval, the percentage (90.0%) of mice showing novel arm preference in 3-NP treatment group was significantly higher than the random chance level (50%), although it was only slightly higher than that (83.3%) in control group. On day 45 after 3-NP treatment, mice failed to choose unfamiliar novel arm as first choice, and the same occured in the control group. (3) For both post-intoxicated (on day 15 and day 45 following 3-NP treatment) and control groups, the duration in the novel arm and the frequency of entering it, were longer and higher compared with familiar start and other arms. For these mice that recently recovered from motor defects following 3-NP intoxication, no spatial memory deficits were observed through Y-maze Test.

Conclusion

Kunming mice used in our assays might possess resistance to cognitive impairment induced by 3-NP, which is consistent with previous findings in Swiss EPM-M1 mice.