全身炎性反应综合征在乙型肝炎肝硬化合并腹水患者住院结局中的临床意义

目的探讨全身炎性反应综合征(SIRS)在乙型肝炎肝硬化合并腹水住院患者中的发生率及其对患者住院结局的影响。方法收集2013年1月至2018年1月东南大学医学院附属南京市第二医院住院的乙型肝炎肝硬化腹水患者的临床资料,分析SIRS的发生率及其与患者临床指标、住院期间出现死亡及门静脉高压并发症(包括食管胃底静脉曲张破裂出血、肝性脑病、肝肾综合征)的关系,分析乙型肝炎肝硬化合并腹水患者住院期间发生死亡和门静脉高压并发症的预测因素。结果乙型肝炎肝硬化合并腹水住院患者共461例,其中出现SIRS的有185例,发生率为40.1%;合并SIRS组患者与未合并SIRS组相比,存在较高的黄疸发生率、细菌感染率、血清胆红素(TBil)、国际标准化比值(INR)、Child-Pugh评分、MELD评分以及较长的住院时间,存在较低的血红蛋白浓度(Hb)、血小板(PLT)计数、钠离子浓度,差异均有统计学意义(P<0.05)。住院期间,共计22例患者死亡(5.8%),8例发生消化道出血(1.7%),4例发生1型肝肾综合征(0.9%),20例发生肝性脑病(4.3%)。SIRS的发生与患者的死亡(P<0.001)及门静脉高压并发症的出现(P<0.001)均有关。MELD评分可同时预测死亡和门静脉高压相关并发症的发生(P<0.001),而SIRS和血红蛋白可预测门静脉高压并发症的发生(P<0.05)。结论SIRS在乙型肝炎肝硬化合并腹水住院患者中较为常见,可加重患者肝损害,导致其住院期间的病死率和门静脉高压并发症的发生率增高,SIRS的存在可预测患者门静脉高压并发症的发生。     

爬梯运动提高Presenilin1/Presenilin2双敲鼠的学习记忆能力

目的 Presenilin1/Presenilin2双基因敲除(PS1/PS2DKO)可导致小鼠学习记忆能力受损,该文主要研究跑台运动和爬梯运动对PS1/PS2 DKO小鼠认知能力的影响,并通过检测运动前后各组小鼠体内神经胶质酸性蛋白(GFAP)、丙二醛(MDA)、超氧化物歧化酶(SOD)等含量的变化,探讨2种运动方式对DKO小鼠认知能力受损的干预效果及其可能的分子机制.方法 将6个月龄雄性DKO小鼠及其同窝对照小鼠(CON小鼠)分为4组,分别为CON不运动组、DKO不运动组、DKO跑台组和DKO爬梯组.对DKO跑台组小鼠进行10周的跑台训练,对DKO爬梯组小鼠进行10周的爬梯训练.运动结束后以开场实验、新异物体识别实验和恐惧条件反射实验测试各组小鼠的运动能力和学习记忆能力;用Western blotting、硫代巴比妥酸法、黄嘌呤氧化酶法检测各组小鼠GFAP、MDA、SOD含量的变化.结果 爬梯运动可明显改善DKO小鼠的恐惧学习记忆能力;跑台运动和爬梯运动均可降低DKO小鼠前脑中GFAP的含量,但前者也会增加前脑中脂质过氧化程度;而跑台运动和爬梯运动对DKO小鼠前脑中的超氧化物歧化酶活性无明显影响.结论 爬梯运动可以改善DKO小鼠的恐惧学习记忆能力,前脑中星型胶质细胞活化程度的降低可能是其分子机制之一.跑台运动对DKO小鼠的学习记忆能力无影响,究其原因可能是跑台运动后DKO小鼠前脑产生大量的氧自由基,其导致的脂质过氧化引起神经细胞损伤,从而抵消了跑台运动对DKO小鼠学习记忆能力的改善作用.     

Presenilin1/Presenilin2双基因敲除小鼠中氧化损伤增加

目的观察3,6,9,12月龄presenilin1和presenilin2双敲除小鼠（dKO）脑组织氧化损伤情况,探讨氧化损伤与presenilins功能丧失所引起的阿尔茨海默病样症状之间的关系。方法酶联免疫反应（ELISA）检测dKO小鼠大脑皮层中Aβ42水平和尿液中8-羟基脱氧鸟苷（8-hydroxy-2-deoxyguanosine,8-OHdG）水平;硫代巴比妥酸法检测脂质过氧化水平,分光光度计测定DNPH法检测蛋白质损伤水平;试剂盒法检测超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-PX）活性。结果与对照组相比,dKO小鼠大脑皮层中Aβ42水平显著降低。同时,除了在3月龄dKO小鼠大脑皮层中发现脂质过氧化水平有显著增加外,蛋白质损伤在各年龄段dKO小鼠中均没有明显变化。ELISA检测结果显示尿液中游离的8-OHdG水平在各年龄段的dKO小鼠中均显著降低。SOD和GSH-PX活性均无明显变化,只有9月龄dKO小鼠中的GSH-PX活性有显著增高。结论氧化损伤特别是DNA损伤参与dKO小鼠神经退行性症状的发生过程;由于dKO小鼠大脑皮层中没有Aβ42的沉积,推测造成氧化损伤的原因可能是由活化的小胶质细胞和星形胶质细胞所释放的免疫因子介导的。     

Oxidative damage increased in presenilin1/presenilin2 conditional double knockout mice

Objective

This report aims to describe the oxidative damage profile in brain of presenilin1 and presenilin2 conditional double knockout mice (dKO) at both early and late age stages, and to discuss the correlation between oxidative stress and the Alzheimer-like phenotypes of dKO mice.

Methods

The protein level of Aβ₄₂ in dKO cortex and free 8-OHdG level in urine were measured by ELISA. Thiobarbituric acid method and spectrophotometric DNPH assay were used to determine the lipid peroxidation and protein oxidation in cortex, respectively. SOD and GSH-PX activities were assessed by SOD Assay Kit-WST and GSH-PX assay kit, separately.

Results

Significant decrease of Aβ₄₂ was verified in dKO cortex at 6 months as compared to control mice. Although lipid peroxidation (assessed by MDA) was increased only in dKO cortex at 3 months and protein oxidation (assessed by carbonyl groups) was basically unchanged in dKO cortex, ELISA analysis revealed that free 8-OHdG, which was an indicator of DNA lesion, was significantly decreased in urine of dKO mice from 3 months to 12 months. Activities of SOD and GSH-PX in dKO and control cortices showed no statistical difference except a significant increase of GSH-PX activity in dKO mice at 9 months.

Conclusion

Oxidative damage, especially DNA lesion, was correlated with the neurodegenerative symptoms that appeared in dKO mice without the deposition of Aβ₄₂. Triggers of oxidative damage could be the inflammatory mediators released by activated microglia and astrocytes.