地塞米松通过线粒体途径诱导成骨细胞凋亡的研究

目的观察地塞米松对离体成骨细胞凋亡的影响,探讨地塞米松对成骨细胞凋亡的分子作用机制。方法采用不同浓度地塞米松(10~(-8)、10~(-6)、10~(-4)mol/L)干预SD大鼠离体成骨细胞,DAPI染色观察细胞核形态,透射电镜观察细胞核及线粒体形态,流式细胞术检测细胞凋亡率,JC-1荧光探针检测线粒体跨膜电位。结果 10~(-8)、10~(-6)、10~(-4)mol/L地塞米松干预24 h后,DAPI染色发现,10~(-8)mol/L地塞米松组的成骨细胞很少发生凋亡,10~(-6)mol/L和10~(-4)mol/L地塞米松组的成骨细胞凋亡明显,地塞米松的浓度越高,核固缩、核裂解等凋亡现象越明显;透射电镜观察发现,随着地塞米松浓度增加,细胞核固缩明显,线粒体肿胀、空泡样变化现象增多;成骨细胞的凋亡率随着地塞米松浓度的增加而逐渐增高,与空白对照组相比,10~(-8)mol/L地塞米松组细胞凋亡率无明显升高(P0.05),10~(-6) mol/L和10~(-4)mol/L地塞米松组的成骨细胞凋亡率分别较空白对照组增加7.240%和31.173%(P0.05);随着地塞米松浓度的增加,线粒体膜电位逐渐减低,与空白对照组相比较,10~(-8)mol/L地塞米松组细胞膜电位下降不明显(P0.05),10~(-6) mol/L和10~(-4)mol/L地塞米松组膜电位下降分别较空白对照组降低6.814%和17.846%(P0.05)。结论地塞米松通过激活线粒体途径诱导成骨细胞凋亡,存在浓度依赖性。     

Long-Term Intravitreal Dexamethasone Implant Outcomes in Uveitis

ABSTRACT

Purpose: To describe the long-term clinical outcomes in a cohort of uveitic eyes treated with the intravitreal dexamethasone implant (Ozurdex; Allergan, Inc).

Methods: Seventy-nine (63 patients) receiving 134 implant injections over 82 months were included. Indication, visual acuity (VA), intraocular pressure (IOP), vitreous haze score (VHS), central retinal thickness (CRT), time to reinjection, systemic treatments, and complications data were recorded.

Results: The cumulative probability of VA improvement was 80% at 1 month and 90% at 12 months, and it was maintained until 60 months. Eyes with baseline vitritis (VHS >0.5; 68%) had a probability of VHS improvement of 33% at 1 month, 75% at 12 months, and 85% at 60 months. The probability of CRT improvement was 33% at 1 month, 75% at 12 months, and 85% at 60 months. The most frequent adverse event was moderate IOP elevation (≥25 mmHg) in 30.3%, no cases of retinal detachment or endophthalmitis were observed.

Conclusions: The dexamethasone implant provides favorable VA, CRT, and VHS long-term outcomes in uveitis with a reduced rate of severe adverse events.     

Intranasal Dexamethasone Reduces Mortality and Brain Damage in a Mouse Experimental Ischemic Stroke Model

Neuroinflammation triggered by the expression of damaged-associated molecular patterns released from dying cells plays a critical role in the pathogenesis of ischemic stroke. However, the benefits from the control of neuroinflammation in the clinical outcome have not been established. In this study, the effectiveness of intranasal, a highly efficient route to reach the central nervous system, and intraperitoneal dexamethasone administration in the treatment of neuroinflammation was evaluated in a 60-min middle cerebral artery occlusion (MCAO) model in C57BL/6 male mice. We performed a side-by-side comparison using intranasal versus intraperitoneal dexamethasone, a timecourse including immediate (0 h) or 4 or 12 h poststroke intranasal administration, as well as 4 intranasal doses of dexamethasone beginning 12 h after the MCAO versus a single dose at 12 h to identify the most effective conditions to treat neuroinflammation in MCAO mice. The best results were obtained 12 h after MCAO and when mice received a single dose of dexamethasone (0.25 mg/kg) intranasally. This treatment significantly reduced mortality, neurological deficits, infarct volume size, blood–brain barrier permeability in the somatosensory cortex, inflammatory cell infiltration, and glial activation. Our results demonstrate that a single low dose of intranasal dexamethasone has neuroprotective therapeutic effects in the MCAO model, showing a better clinical outcome than the intraperitoneal administration. Based on these results, we propose a new therapeutic approach for the treatment of the damage process that accompanies ischemic stroke.Electronic supplementary materialThe online version of this article (10.1007/s13311-020-00884-9) contains supplementary material, which is available to authorized users.     

甘露醇在腰椎间盘突出症术后“反跳痛”治疗中的应用

目的：探讨甘露醇注射液在腰椎间盘突出症术后"反跳痛"治疗中的临床疗效。方法：收集2014年3月到2017年3月在我院行椎间盘镜下髓核摘除术的患者共82例，将所有患者随机分为3组，其中对照组27例，甘露醇组30例，地塞米松组25例。术前记录患者下肢痛的视觉模拟评分（VAS评分），腰椎日本骨科协会评估治疗分数（JOA评分）。术后甘露醇组使用20%甘露醇注射液125 mL静脉滴注，每8小时一次，连用一周。地塞米松组使用20 mg地塞米松磷酸钠注射液加入葡萄糖注射液，3 d后地塞米松减量为10 mg，连用一周。记录术后下肢痛的VAS评分和腰椎JOA评分，以及是否有下肢"反跳痛"及其VAS评分和持续时间。结果：3组患者手术前后VAS评分和JOA评分没有显著性差异（P>0.05）。3组患者术后下肢"反跳痛"的发生率没有显著性差异（P>0.05）。地塞米松可减少术后下肢痛的VAS评分，甘露醇无此效果，差异有显著性差异（P<0.05）。结论：甘露醇不能减少术后下肢"反跳痛"的发生率，疼痛程度和持续时间。     

SMILE术中角膜帽下地塞米松平衡液冲洗与否的早期临床观察

目的观察飞秒激光小切口角膜基质透镜取出术(SMILE)中角膜帽下地塞米松平衡液冲洗与否对术后视觉质量及角膜组织结构形态的影响。方法选择拟进行双眼SMILE手术的24例(48眼)纳入研究,每例患者随机选取一眼透镜取出后,行地塞米松平衡液冲洗角膜帽下基质腔隙(实验组),对侧眼不冲洗(对照组)。分别于术后第1天、第7天及1个月对比观察两组的裸眼视力、屈光状态、角膜中央厚度(CCT)、眼压(NCT);同时利用共焦显微镜及前段光学相干断层扫描(OCT)检查对比观察两组角膜上皮细胞、神经纤维、基质细胞、内皮细胞形态结构。采用配对t检验比较两组的裸眼视力、屈光状态等各指标有无差异。结果术后第1天、第7天及1个月两组间裸眼视力比较:实验组为4.99±0.07、5.06±0.08、5.05±0.06;对照组为5.01±0.07、5.05±0.08、5.06±0.09;3个时间点两组间裸眼视力均无统计学差异(P均>0.05);术后第1天、第7天及1个月的屈光度(SE,D):实验组为0.03±0.49、0.1±0.37、0.02±0.4;对照组为0.09±0.54、0.19±0.48、0±0.52,3个时间点两组间SE比较均无统计学差异(P均>0.05)。共焦镜检查不同时间点比较:角膜上皮层细胞密度[术前(4578.73±268.40,4539.57±329.25)个/mm^2,术后第1天(4565.21±247.31,4627.23±271.03)个/mm^2,术后第7天(4640.01±246.79,4517.71±281.43)个/mm^2];角膜内皮细胞密度[术前(2541.50±259.59,2443.52±305.58)个/mm^2,术后第1天(2387.01±248.55,2495.27±238.52)个/mm^2,术后第7天(2484.49±223.71,2482.53±323.82)个/mm^2],术前术后两组间均无统计学差异(P>0.05);角膜上皮下神经纤维丛术前术后两组间比较无明显变化;切削界面高反光物两组间比较没有明显差异;角膜前基质细胞密度[术前(789.51±67.17,802.03±67.94)个/mm^2,术后第1天(889.37±60.62,912.27±95.87)个/mm^2,术后第7天(796.67±75.03,818.39±59.65)个/mm^2]在术后第1天、第7天较术前均有增加,但两组之间没有统计学差异(P>0.05),术后1 d两组前基质细胞较术前增加,有统计学差异(P<0.05);角膜后基质细胞术后各时间点两组间比较无统计学差异(P>0.05)。角膜OCT在术后1 d、7 d两组在角膜帽下均未出现明显层间间隙和积液,两组间角膜中央厚度无统计学差异(P>0.05)。结论SMILE术中地塞米松平衡液角膜帽下冲洗对术后裸眼视力、屈光度及角膜组织结构形态无明显影响。     

甲基强的松龙冲击疗法治疗放射性脑水肿的疗效

目的 探讨甲基强的松龙（MP）冲击疗法治疗放射性脑水肿（RCE）的临床疗效。方法 回顾性分析2001~2012年收治46例的RCE的临床资料。26例给予MP冲击疗法（观察组），20例给予地塞米松等传统治疗（对照组）。治疗30 d，评估临床疗效，分为显效、有效、无效、进展；总有效=显效+有效；根据中华医学会第二次全国脑血管病学术会议制定的评分标准评定神经功能缺损程度，分为基本治愈、显著进步、进步、无变化、恶化、死亡；采用修订的Barthel指数评定法评定日常生活活动能力。结果 观察组总有效率（90.91%）与对照组（72.22%）无统计学差异（P>0.05），但是显效率（36.26%）明显高于对照组（5.56%；P<0.05）。治疗后30 d，观察组神经功能评分[（8.15±3.25）分]与对照组[（7.65±3.77）分]较治疗前均明显降低（P<0.05），但两组之间无统计学差异（P>0.05）。治疗后30 d，观察组Barthel指数[（84.04±12.41）分]与对照组[（84.50±7.59）分]较治疗前均明显增高（P<0.05），但是两组之间无统计学差异（P>0.05）。观察组不良反应发生率（42.31%）与对照组（45.00%）无统计学差异（P>0.05）。结论 MP冲击疗法和传统地塞米松疗法对RCE均具有治疗作用，但MP冲击疗法对颅内压增高症状的改善更快、更明显     

Melatonin prevents dexamethasone‐induced testicular oxidative stress and germ cell apoptosis in golden hamster,Mesocricetus auratus

This study investigated the protective effect of melatonin on dexamethasone (Dex), an extensively used anti‐inflammatory and immunosuppressive synthetic glucocorticoid, induced testicular oxidative stress and germ cell apoptosis in golden hamster. Hamsters were randomly divided into four groups (n = 7): group I – control; group II – melatonin treated (10 mg kg^?1 day^?1); group III – Dex treated (7 mg kg^?1 day^?1) and group IV – combination of Dex and melatonin. All the injections were administered intraperitoneally for seven consecutive days. The histopathological changes, specific biochemical markers, including antioxidative enzymes, plasma melatonin level and the markers for germ cell apoptosis were evaluated. Dex administration decreased antioxidant enzyme activities (SOD, CAT, GSH‐P_X), plasma melatonin level and melatonin receptor (MT1) expression with a concomitant increase in lipid peroxidation (TBARS) and altered testicular histopathology which might culminate into increased germ cell apoptosis as evident from increased Bax/Bcl‐2 ratio and caspase‐3 expression. However, melatonin pre‐treatment enhanced enzyme activities for SOD, CAT, GSH‐P_X with a simultaneous decrease in Bax/Bcl‐2 ratio and caspase‐3 expression. Our findings clearly suggest that melatonin improved defence against Dex‐induced testicular oxidative stress and prevented germ cell apoptosis, suggesting a novel combination therapeutic approach for management of male reproductive health.     

骨桥蛋白在哮喘小鼠肺组织中的表达及地塞米松的干预作用

目的 探讨哮喘气道炎症与骨桥蛋白(OPN)表达的相关性,以及地塞米松(DXM)对OPN表达的影响.方法 50只小鼠随机分为正常对照组、不同程度哮喘组(卵清蛋白OVA激发1周和2周组)及DXM治疗1周和2周组,每组10只;OVA致敏、激发建立急性哮喘模型;苏木精-伊红染色观察各组小鼠气道炎症情况;ELISA法检测血清OVA-sIgE水平;免疫组化和Western blot法分别定位和定量分析肺组织OPN表达;Real-time PCR检测肺组织OPN mRNA水平.结果 哮喘组气道病理学改变较对照组和DXM组明显,且OVA激发2周哮喘组改变较激发1周组明显.哮喘组血清OVA-sIgE水平较对照组和DXM组明显升高(PPPP结论 OPN可能是哮喘发病机制中的重要因素,哮喘气道炎症越重,OPN表达水平可能越高;DXM可能通过抑制OPN的表达来减轻哮喘炎症.