【摘要翻译】 一 氧化氮合酶( NOS) -2( NOS-2) 的诱导和一氧化氮产物增加是过敏性气道疾病的共同特征。严重哮喘与气道S-亚硝基硫醇减少相关。S-亚硝基硫醇是NO的生化产物, 可通过促炎症转录因子NF-κB 的S-亚硝基化抑制炎症反应。因此, 重建气道S-亚硝基硫醇对治疗可能有益。我们对此假设在以卵清蛋白诱导的过敏性炎症大鼠模型中进行验证。未使用或使用卵清蛋白致敏的动物均在卵清蛋白激发前于气管内灌注S-亚硝基谷胱甘肽( GSNO;50 μl, 10 mM) , 并在48 h 以后进行分析。GSNO 给药增加了肺组织S-亚硝基硫醇水平。与对照组比, GSNO 降低了卵清蛋白致敏动物NF-κB 的活性, 但对支气管肺泡灌洗细胞总数、分类计数及杯状细胞化生标记物均无显著影响。GSNO给药也改变了HIF-1 的活性, 导致未致敏大鼠HIF-1 活化,但抑制卵清蛋白致敏大鼠的HIF-1 活性。我们使用NOS-2基因敲除小鼠来评价内源性一氧化氮合成酶-2 在调节NF-κB和( 或) HIF-1 活性及气道过敏性炎症的作用。尽管在NOS-2 基因敲除小鼠中卵清蛋白诱导的NF-κB 活力轻度增高, 这与支气管肺泡灌洗中性粒细胞轻度增加有关, 其他的过敏性炎症指标和HIF-1 活性在NOS-2 基因敲除及野生型小鼠之间却无明显相差。总体来说, 我们的研究表明GSNO灌注能抑制气道过敏性炎症中NF-κB 活性, 但是并不能显著地影响大部分炎症及杯状细胞化生指标, 这样可能因为对其他信号通道( 比如HIF-1) 的影响而限制了它的治疗价值。【述评】 GSNO 是近年哮喘治疗研究的热点。既往的研究发现GSNO 在哮喘治疗中有一定前景。本研究却发现GSNO 气管内滴注虽能抑制过敏性气道炎症中NF-κB 活性,但并不能显著抑制气道炎症反应及杯状细胞化生这两个哮喘关键病理改变, 可能与GSNO 同时影响了HIF-1 等其他信号通路有关。该研究表明GSNO 对哮喘气道炎症治疗效果有限, 同时表明哮喘气道炎症调控机制较为复杂, 治疗药物的设计需考虑多种信号通路对哮喘气道炎症的影响。
ObjectivesTo detect expressions of trefoil factor 1 (TFF1) and TFF3 in the mice with acute allergic airway disease (AAD) after different interventions, and explore primitively the effect of recombinant TFF3 on airway inflammation and mucous secretion.MethodsForty BALB/c mice were randomly divided into 5 groups, each group with 8 mice, ie. a normal saline control group (group A), an AAD group (group B), a budesonide intervention group (group C), a recombinant TFF3 intervention group (group D), and a budesonide+recombinant TFF3 intervention group (group D). The BALB/c mice were sensitized and challenged with ovalbumin to induce AAD. Lung tissue sections were stained with hematoxylin-eosin staining for assessment of airway inflammation, and immunohistochemistry was used for detecting TFF1/TFF3 expression in the airway. Alcian blue stain was applied to determine mucous secretion.ResultsAirway inflammation score and airway mucous secretion: Group B was significantly more than group A (P<0.01); Group C was less than group B (P<0.05), and there was no significant difference between group D and group B (P>0.05); There was no significant difference between group C and group E (P>0.05). Expression of TFFs: TFF1 and TFF3 were expressed in epithelial cells, goblet cells and submucosal gland cells of bronchi and bronchioles in all groups; The expressions of TFF1 and TFF3 in group B were significantly higher than those in group A (P<0.01), while the expressions of TFF1 and TFF3 in group C were lower than those in group B (P<0.05). TFF1 expression in airway epithelium was positively correlated with inflammatory score (r=0.876, P=0.000) and mucin expression (r=0.807, P=0.000). TFF3 level was positively correlated with inflammatory score (r=0.654, P=0.006) and mucin expression (r=0.666, P=0.005).ConclusionsOvalbumin-induced acute allergic airway inflammation significantly increases TFF1/TFF3 expression. Intranasal TFF3 treatment may not influence airway inflammation and mucus secretion. Inhaled corticosteroids to some extent inhibit expressions of TFF1 and TFF3, simultaneously suppress airway inflammation and mucus secretion in the mouse model of acute AAD .
摘要:目的:探讨复方丹参加西咪替丁治疗过敏性紫癜(HSP)临床疗效。方法:60例患儿随机分为对照组和治疗组各30例。对照组常规治疗,治疗组加用复方丹参和西咪替丁治疗。结果:治疗组总有效率为90.0%,明显高于对照组53.3%,且治疗组紫癜性肾炎(HSPN)发生率(10.0%)明显低于对照组(36.7%),Plt;0.01。结论:复方丹参加西咪替丁能提高HSP患儿疗效,减少肾损害,促进患儿病情康复。
ObjectiveTo systematically review the efficacy and safety of mycophenolate mofetil (MMF) for Henoch-Schonlein purpura nephritis (HSPN). MethodsDatabases such as PubMed, EMbase, CENTRAL, VIP, CNKI, CBM and WanFang Data were electronically searched for comprehensively collecting the randomized controlled trials (RCTs) on the efficacy and safety of MMF for HSPN from inception to December, 2013. Two reviewers independently screened studies according to the inclusion and exclusion criteria, extracted data and evaluated the methodological quality of the included studies. Then meta-analysis was performed using RevMan 5.1 software. ResultsA total of 10 RCTs involving 426 patients (231 in the trial group and 195 in the control group) were included. The trial group was treated with MMF and corticosteroids, and the control group was treated with corticosteroids monotherapy or combined with cyclophosphamide (CTX), leflunomide (LEF), or azathioprine (AZA). The results of meta-analysis showed that, as for efficacy, no significant difference was found between the two groups after six-mouth treatment (OR=1.36, 95%CI 0.67 to 2.73, P=0.85), while after twelve-mouth treatment, MMF was superior to CTX with a significant difference (OR=6.58, 95%CI 2.45 to 17.33, P=0.002). In addition, the efficacy of MMF was still superior to the azathioprine group, but not better than either LEF or prednisone monotherapy. Lower incidence of side effects were found in the MMF group, compared with the CTX group (OR=0.25, 95%CI 0.13 to 0.45, P < 0.000 01) and the prednisone monotherapy group (OR=0.26, 95%CI, 0.09 to 0.79, P=0.02), while there was no significant difference between the MMF group and the LEF group in side effects. ConclusionBased on the current evidence, the efficacy of MMF for HSPN is better than CTX, and its side effects are less than those of CTX and prednisone.