地塞米松预处理对氧糖剥夺大鼠血脑屏障通透性的影响

目的探讨地塞米松(dexamethasone,DEX)对氧糖剥夺(oxygen glucose deprivation,OGD)条件下大鼠血脑屏障通透性的影响。方法提取纯化大鼠脑微血管内皮细胞,建立血脑屏障OGD模型。在OGD不同时间点(0、30、60 min),以及DEX预处理OGD 60min时,应用辣根过氧化物酶渗漏实验分析血脑屏障的通透性;应用RT-PCR和western blot法分析大鼠脑微血管内皮细胞的紧密连接相关蛋白claudin-5的mRNA和蛋白的表达变化;同时应用免疫荧光方法观察细胞膜上claudin-5的变化。结果与对照组相比,OGD 30、60min,辣根过氧化物酶流量均显著升高;与OGD 60min相比,DEX预处理显著降低了辣根过氧化物酶流量。与对照组相比,OGD30、60min,claudin-5的mRNA和蛋白表达水平均显著降低;与OGD 60min相比,DEX预处理显著增加了claudin-5的mRNA和蛋白表达。免疫荧光观察claudin-5在细胞膜上的表达,与对照组相比,OGD 60min时claudin-5的表达明显减少,DEX预处理后显著增加了claudin-5的表达。结论 DEX预处理降低了OGD条件下的血脑屏障通透性,其机制之一是DEX增加紧密连接相关蛋白claudin-5的表达。     

Organs/Systems Potentially Involved In One Model Of Programmed Hypertension In Sheep

1. When pregnant ewes and their fetuses are exposed to the synthetic glucocorticoid dexamethasone for 2 days early in pregnancy (days 26-28; term 145-150 days), female offspring have increased blood pressure relative to a control group. In one series, this was shown to be due to increased cardiac output, concomitant with a reset mean arterial pressure/heart rate reflex. The first group of such animals had, by the age of 7 years, left ventricular hypertrophy and reduced cardiac functional capacity. 2. The elevation in blood pressure is not maintained by any change in the peripheral renin-angiotensin system (RAS). 3. There is, however, preliminary evidence that some aspects of local RAS (particularly in the kidney and brain) could have participated in the 'programming' event. The levels of mRNA for angiotensin II receptors (AT1, AT2) and angiotensinogen are increased in the kidney of such dexamethasone-treated fetuses in late gestation (130 days), some 100 days after steroid treatment. Similar increases in AT1 mRNA in the medulla oblongata of the fetal brain and large increases of mRNA for angiotensinogen occur in the hypothalamus. 4. These findings, together with evidence from the literature, suggest that both the kidney and parts of the brain are affected by events that also 'program' high blood pressure in the offspring of animals in which the intra-uterine environment has been perturbed at some stage.     

淀粉样变治疗学研究的最新进展

既往10—15年中系统性淀粉样变新治疗的发展取得了实质性进展。这些进展改善了患者的转归，但亦带来新的临床问题。例如，由于淀粉样轻链（K或入）（AL）淀粉样变对自体造血干细胞移植的作用不太肯定，为此正在开发广泛途径的治疗研究和提供最佳支持治疗。现认为淀粉样前体和成熟原纤维促使淀粉样变相关的器官病变，显示完全清除AL淀粉样变患者促淀粉样（amyloidogenic）轻链生成的重要性，同时治疗前后需作淀粉样前体蛋白和器官病变标记的监测。     

Dickkopf‐1 is involved in dexamethasone‐mediated hair follicle regression

The stress‐related neurohormones including glucocorticoids (GCs) are secreted by hair follicles (HFs), and GCs suppress murine hair growth in vivo. In this study, we found that dexamethasone (Dex), a synthetic GC, increased the expression of dickkopf‐1 (DKK1), a known catagen inducer, in dermal papilla (DP) cells, but not in follicular keratinocytes. The neutralizing DKK1 antibody significantly attenuated the Dex‐induced inhibition of human hair shaft elongation. In addition, the neutralizing Dkk1 antibody delayed Dex‐induced catagen in mice. Collectively, our data strongly suggest that stress‐related neurohormones cause DP cells to secrete DKK1, thereby leading to stress‐associated disturbances in hair growth.     

姜辣素对顺铂致大鼠异嗜模型行为的作用

目的研究姜辣素对顺铂所致大鼠异嗜高岭土模型的影响并观察外周和中枢c-fos蛋白的表达。方法大鼠随机分成正常对照组、模型组、昂丹司琼+地塞米松组、阿瑞吡坦+地塞米松组、姜辣素组及姜辣素+地塞米松组,24 h及72 h记录各组摄食量及食高岭土量。免疫组化方法观察脑和回肠中c-fos蛋白的表达。结果 24 h内,姜辣素组、姜辣素+地塞米松组摄食量增加,啃食高岭土量减少,姜辣素组与姜辣素+地塞米松组相比摄食量增加(P<0.05);48～72h内,姜辣素组食高岭土量减少(P<0.05)。姜辣素组、姜辣素+地塞米松组c-fos阳性表达颗粒的灰度值明显高于模型组(P<0.05)。结论姜辣素可促进摄食并可抑制顺铂所致的大鼠异嗜高岭土行为,地塞米松对姜辣素无辅助作用。     

High-dose dexamethasone regulates interleukin-18 and interleukin-18 binding protein in idiopathic thrombocytopenic purpura

To evaluate the effects of high-dose dexamethasone (HD-DXM) on the balance of interleukin-18 (IL-18) and its endogenous antagonist IL-18 binding protein (IL-18BP) in ITP patients, IL-18, IL-18BP as well as IFN-γ, IL-4 plasma levels and platelet counts were determined in 17 ITP patients receiving DXM 40 mg/day for four consecutive days and in 24 healthy subjects. Using RT-PCR, the mRNA expression of IL-18, IL-18BP, IFN-γ, IL-4, T-box (T-bet) and GATA-binding protein 3(GATA-3) were studied in all subjects. The in vitro effects of DXM on IL-18BP and IL-18 of peripheral blood mononuclear cells (PBMCs) were studied by ELISA. HD-DXM administration increased IL-18BP and reduced IL-18 expression significantly (p<0.05), which resulted in a downregulation of IL-18/IL-18BP ratio p<0.05). In vitro, DXM had a significant effect on secretion of IL-18BP while diminishing IL-18 release from cultures of PBMCs. These results suggest that downregulation of IL-18/IL-18BP might account for its clinical efficacy of HD-DXM in active ITP.     

Perineural dexamethasone does not enhance the analgesic efifcacy of ultrasound-guided subcostal transversus abdominis plane block during laparoscopic cholecystectomy

BACKGROUND: Ultrasound-guided transversus abdominis plane (TAP) block is an adjunct therapy to provide effective postoperative analgesia in abdominal surgical procedures. Dexamethasone is a supplement agent that can improve the efifcacy of local anesthesia. However, information about its additive effect is limited. This study aimed to compare the an-algesic efifciency using ultrasound-guided TAP block with and without perineural dexamethasone for patients who under-went laparoscopic cholecystectomy.
METHODS: Sixty patients who underwent laparoscopic cho-lecystectomy were randomly divided into three groups: group I, controls; group II, TAP; and group III, TAP+perineural dexamethasone supplement. The requirement of additional analgesia and the ifrst-time request of rescue-analgesia were recorded after operation and the numerical rating scale was evaluated at speciifc intervals.
RESULTS: Compared to group I, the ifrst-time requirement of rescue-analgesia in groups II and III was signiifcantly delayed (403.0±230.9, 436.0±225.3 vs 152.3±124.7,P<0.01). Compared with those in group I, patients in groups II and III were associ-ated with lower numerical rating scale pain scores (P<0.01) and less postoperative analgesic consumption (P<0.01). There was no signiifcant difference in the variables mentioned above between groups II and III (P>0.05).
CONCLUSION: Perineural dexamethasone has no additive/synergistic effect with subcostal TAP block on analgesic efif-cacy for the patients undergoing laparoscopic cholecystectomy.     

妊娠期肝内胆汁瘀积症的治疗与围产儿预后关系的探讨

目的 :评估熊去氧胆酸 (UDCA)、地塞米松 (DX)治疗妊娠期肝内胆汁瘀积症 (ICP)的疗效及围产儿预后情况。方法 :12 6例患者随机分为UDCA组 (A组 )、DX组 (B组 )和对照组 (C组 ) ,各 4 2例 ,A、B、C 3组血清胆汁酸TBA(10～ 5 0μmol/L)分别为A1组 30例、B1组 2 7例、C1组 2 9例 ;TBA >5 0 μmol/L分别为A2 组 12例、B2 组 15例、C2 组 13例。A组给予UDCA 10 0mg ,3次 /d ,14d为 1个疗程 ;B组给予DX 3mg ,3次 /d ,10d后逐渐减量而停药 ;C组给予口服维生素C 0 .2 g ,连续服用 14d。结果 :A、B组患者治疗后皮肤瘙痒症状明显减轻 (P <0 .0 5 ) ,C组瘙痒症状无变化 ;A、B 2组治疗后血TBA明显下降 (P <0 .0 5 ) ;A2 组下降程度大于B2 组 (P <0 .0 5 ) ,C组稍上升 (P >0 .0 5 ) ;3组内早产、胎儿窘迫、新生儿窒息的发生率与TBA值呈正相关 ,A、B组的发生率明显低于C组 ,差异有显著性 (P <0 .0 5 ) ,A、B组内TBA值低的组 (A1、B1组 )早产、胎儿窘迫、新生儿窒息发生率差异无显著性 (P >0 .0 5 ) ,TAB值高的组 (A2 、B2 组 )早产、胎儿窘迫、新生儿窒息的发生率差异有显著性 (P <0 .0 5 )。结论 :UDCA、DX均能有效治疗ICP ,减少早产、胎儿窘迫、新生儿窒息的发生率 ,对于TBA值高的患者 ,UDCA疗效优于DX ,仅口服维生     

地塞米松影响下颌骨再生修复的相关分子机制研究

目的 探讨抗炎药地塞米松延缓下颌骨缺损骨再生的相关分子机制。方法 建立SD大鼠双侧下颌骨颊舌向贯穿的骨缺损模型,随机分为用药组与生理盐水对照组,分别给予治疗剂量的地塞米松或者等体积的生理盐水,连续给药5 d后的第1、3、6、10、17天分别处死大鼠并取双侧下颌骨,用免疫组化染色,分别检测骨再生修复不同阶段炎症因子环氧化酶-2(COX2)、成骨分化关键性调控因子runt相关转录因子-2(RUNX2)及骨钙蛋白(BGP)的表达。结果 炎症因子COX2及成骨因子RUNX2、BGP在骨再生修复过程中的表达存在相同的变化趋势,半定量数据表明RUNX2、BGP表达和COX2表达存在正相关关系。结论 抗炎药地塞米松通过抑制炎症阶段COX2表达,从而抑制成骨分化关键性调控因子RUNX2/BGP表达,导致下颌骨缺损再生修复的延迟。     

来氟米特和地塞米松对正常人外周血Th17和Th1细胞的免疫调节作用

目的:探讨来氟米特活性代谢产物A771726和地塞米松对正常人外周血辅助性T细胞Th17和Th1细胞亚群的免疫调节作用.方法:体外分离正常健康人外周血CD4+T淋巴细胞,分别与不同剂量的A771726(15、30、60 μg/ml)和地塞米松(10-6、10-7、10-8mol/L)体外共培养,采用流式细胞技术(FCM...