Lipopolysaccharide mouse models for Parkinson’s disease research: a critical appraisal

Parkinson’s disease, the most common movement disorder, has a strong neuroinflammatory aspect. This is evident by increased pro-inflammatory cytokines in the serum, and the presence of activated microglial cells, and inflammatory cytokines in the substantia nigra of post-mortem brains as well as cerebrospinal fluid of Parkinson’s disease patients. The central and peripheral neuroinflammatory aspects of Parkinson’s disease can be investigated in vivo via administration of the inflammagen lipopolysaccharide, a component of the cell wall of gram-negative bacteria. In this mini-review, we will critically evaluate different routes of lipopolysaccharide administration (including intranasal systemic and stereotasic), their relevance to clinical Parkinson’s disease as well as the recent findings in lipopolysaccharide mouse models. We will also share our own experiences with systemic and intrastriatal lipopolysaccharide models in C57BL/6 mice and will discuss the usefulness of lipopolysaccharide mouse models for future research in the field.Key Words: C57BL/6 mice, intranasal models, lipopolysaccharide models, neuroinflammation, Parkinson’s disease, stereotaxic models, substantia nigra, systemic models     

黄芪沙参煎剂对博莱霉素诱导的大鼠肺纤维化模型的干预作用

目的：观察中药黄芪沙参煎剂对肺纤维化大鼠病理、肺泡灌洗液中细胞因子（TGF-β1）表达的影响,探讨黄芪沙参煎剂作用机制,为其临床治疗肺纤维化提供实验依据。方法：取体重190-210g的健康雌性SD大鼠90只,采用随机数字表随机分为6组,每组15只。博莱霉素（B组）、黄芪沙参煎剂高剂量组（H组）、中剂量组（M组）、低剂量组（L组）、强的松组（P组）、生理盐水组（N组）,各组大鼠于造模后第7、14和28天分别随机处死5只。行HE染色、Masson三色染色;右肺支气管肺泡灌洗,收集灌洗液（BALF）,用ELISA法测BALF上清液细胞因子TGF-β1的表达。结果：H组、M组、P组与B组早期肺泡炎和晚期肺纤维化程度比较,差异有统计学意义（P〈0.01）;第7、14、28天P组、H组、M组的BALF中TGF-β1水平与Β组相比差异有显著统计学意义（Ρ〈0.01）。结论：黄芪沙参煎剂具有与强的松相似的疗效,但副反应小、服用方便,可以明显减少肺泡炎症及肺纤维化形成。黄芪沙参煎剂治疗肺纤维化机制可能与早期抑制炎症细胞浸润,减少炎症细胞分泌释放细胞因子TGF-β1,从而抑制成纤维细胞产生胶原和ECM积聚,起到对肺纤维化的治疗作用。     

活血解毒方对缺氧/复氧所致心肌细胞凋亡的影响＊

目的 研究活血解毒方对缺氧/复氧（H/R）所致的心肌细胞凋亡的影响。方法 体外培养H9C2心肌细胞并分成正常对照组（Control组）、缺氧复氧组（H/R组）、H/R + 活血解毒中药组、LY294002组和活血解毒中药 + LY294002组，其中正常对照组给予DMEM培养基培养，缺氧复氧组给予缺氧4 h、复氧6 h处理，缺氧复氧 + 活血解毒中药组、LY294002组和活血解毒中药 + LY294002组分别给予活血解毒中药、LY294002、活血解毒中药配合LY294002预处理24 h，然后均给予缺氧4 h、复氧6 h处理。采用CCK8检测各组心肌细胞的存活率，流式细胞术检测各组细胞凋亡水平，电镜观察各组心肌细胞中线粒体、自噬体的变化，Western Blot检测各组细胞凋亡蛋白半胱氨酸天冬氨酸蛋白酶3（Caspase3）、半胱氨酸天冬氨酸蛋白水解酶3（Cleaved caspase3）、β-连环蛋白（β-Catenin）、p-p65、B淋巴细胞瘤-2（B-cell lymphoma-2，Bcl-2）蛋白的表达。结果 活血解毒方预处理显著增加H/R诱导的H9C2心肌细胞凋亡，降低凋亡相关蛋白Cleaved caspase3、β-Catenin、p-p65表达，增加Bcl-2表达。结论 活血解毒方可通过抑制细胞凋亡，降低缺氧/复氧所致的心肌细胞损伤，其作用机制可能与PI3K信号通路相关。     

驻景丸加减方对形觉剥夺性近视小鼠视网膜自噬的影响

目的:探讨驻景丸加减方对形觉剥夺性近视小鼠视网膜自噬的影响。方法:C57BL/6小鼠30只随机分为阴性对照组、近视模型组以及中药干预组,每组10只。除了阴性对照组外,近视模型组、中药干预组小鼠均使用半透明EP管遮盖右眼制成形觉剥夺性近视(FDM)模型;中药干预组灌胃驻景丸加减方混悬液0.546g/(kg·d)(0.15mL/d),阴性对照组、近视模型组灌胃等量生理盐水(0.15mL/d),共4wk。分别于实验开始、实验结束,使用带状检影镜测量小鼠右眼屈光度,A超测量小鼠右眼眼轴长度。实验结束时,取所有小鼠右眼进行检测,免疫荧光法定位和检测视网膜小胶质细胞标志物(Iba1)活性与迁移;透射电镜观察视网膜色素上皮细胞中自噬小体形成情况;Western Blot、实时荧光定量PCR(q-PCR)检测视网膜组织自噬标志物LC3Ⅱ和p62蛋白定量及基因表达情况。结果:实验结束时小鼠右眼屈光度示,近视模型组、中药干预组形成相对近视,近视模型组、中药干预组较阴性对照组显著降低(均P<0.01)。实验结束时,近视模型组、中药干预组眼轴长度较阴性对照组眼轴长度显著增加(P<0.01)。免疫荧...     

Numerical Simulation and Process Optimization on Hot Twist-Stretch Straightening of Ti-6Al-4V Alloy Profile

Ti-6Al-4V profiles prepared by hot extrusion are usually accompanied by bending and twisting. The hot twist-stretch straightening is an effective strategy such that the bending deflection and twisting angle can be simultaneously decreased by a single straightening process. In addition, utilizing stress relaxation effect, the residual stress and springback can be greatly reduced by holding the straightening temperature and strain constant for a period after twist-stretch straightening. In this study, the hot deformation behaviors of the Ti-6Al-4V profile were revealed by experiments. The tensile model was obtained by uniaxial tensile tests within ranges of temperatures (500–700 °C) and strain rates (5 × 10⁻⁵–1 × 10⁻³ s⁻¹). The creep constitutive model was acquired with stress relaxation experiments in ranges of temperatures (500–700 °C) and pre-strain of 1.5%. Then, the coupled thermo-mechanical model of hot twist-stretch straightening was established. Based on orthogonal experiment strategy, the effects of straightening temperature, stretch strain, and holding time on the bending deflection and torsion angle of profile were investigated systematically and the process was optimized. The straightening accuracy is significantly affected by straightening temperature and holding time. By using optimized process parameters in practical straightening experiments, the deflection/length and angle/length after straightening does not exceed 2‰ and 2.5‰°/mm, respectively, which is basically consistent with the numerical simulation result.     

Effect of H2S Corrosion on the Fracture Toughness of the X80 Pipeline Steel Welded Joint

To analyze the causes and mechanisms affecting the fracture toughness of X80 pipeline steel welded joints against H₂S, the fracture toughness of different zones of X80 pipeline steel welded joints in both air and saturated H₂S solution was investigated. The fracture toughness of welded joints degraded significantly in the saturated H₂S solution, where the crack tip opening displacement (CTOD) characteristic value in the coarse grain heat-affected zone (CGHAZ) and weld metal (WM) was only 8% and 12% of that in air, respectively. However, the sub-critical grain heat-affected zone (SCHAZ) showed better resistance to H₂S corrosion, with the CTOD characteristic value reaching 42% of that in air. The resistance of the welded joint to H₂S corrosion was sensitive to microstructures. The grain boundary ferrite (GBF) presented in WM, and the angle of grain boundary orientation in CGHAZ was not conducive to hindering crack propagation. Moreover, the formation of the resultant hydrogen cracks owing to the H₂S corrosion also reduced the fracture toughness of the welded joint.