GRP94、EIF2α在原发型闭角性青光眼小梁中的作用研究

目的 通过检测内质网应激的相关因子 GRP94、EIF2α在原发性慢性闭角型青光眼( PCACG)患者小梁组织中的表达,研究内质网应激在PCACG小梁组织氧化损伤中的作用,探讨PCACG的发病机制。 方法 分别用HE染色法观察实验组及对照组小梁组织镜下显微形态的变化、免疫组化法测定实验组及对照组小梁组织中内质网应激相关因子 GRP94、 EIF2α的表达水平。 结果 HE染色显示,PCACG 患者小梁组织排列不规则,小梁网眼窄小,Schlemm 管腔变窄且不规则。免疫组化结果显示,对照组的小梁网组织GRP94、EIF2α少量表达,实验组小梁组织中GRP94、EIF2α的表达明显增加,差异均具有统计学意义( P<0.05)。 结论 PCACG 患者小梁组织中存在内质网应激,内质网应激EIF2α通道参与了小梁组织的氧化损伤,促进了眼内压的升高。     

趋化因子CCL-19在慢性鼻-鼻窦炎患者鼻黏膜中的表达及意义

目的观察趋化因子CCL-19在慢性鼻-鼻窦炎患者鼻黏膜中的表达及其病理意义。方法不伴鼻息肉的慢性鼻-鼻窦炎患者36例,伴有鼻息肉的慢性鼻-鼻窦炎患者5例,健康对照者12例,分别取鼻腔黏膜或息肉组织标本,Western blot法检测CCL-19蛋白表达活性,比较其在病变鼻黏膜、息肉组织和正常鼻黏膜中的表达差异,探讨其病理意义。结果鼻息肉组织和不伴鼻息肉的慢性鼻-鼻窦炎鼻黏膜组织CCL-19蛋白表达水平均较正常鼻黏膜明显上调,差异有统计学意义(P0.05),水肿型病变黏膜组织尤为显著(P0.05);嗜酸性粒细胞性慢性鼻窦炎CCL-19蛋白表达水平又明显高于非嗜酸性粒细胞性者(P0.05)。结论水肿型慢性鼻窦炎和嗜酸性粒细胞性慢性鼻窦炎病变黏膜CCL-19表达明显上调,提示CCL-19表达活性可能与慢性鼻-鼻窦炎病变组织的嗜酸性粒细胞浸润和组织水肿密切相关。     

miR-204通过内质网应激抑制视网膜母细胞瘤生长作用及机制的研究

目的 探讨miR-204在视网膜母细胞瘤中的表达、对其生长的作用及其分子机制。 方法 通过RT-PCR检测miR204 在视网膜母细胞瘤(Y79)及正常视网膜细胞(ARPE-19)中的表达,并用miR-204 模拟物及抑制物转染Y79 细胞,CCK-8 及流式细胞仪检测Y79 细胞的生存率及凋亡情况, Western blot 法检测GRP78蛋白的表达。 结果 miR-204在视网膜母细胞瘤Y79细胞中呈现低表达,可显著抑制视网膜母细胞瘤的增殖,促进其凋亡,可上调 GRP78蛋白的表达,激活内质网应激途径。 结论 miR-204在视网膜母细胞瘤细胞中表达下调,miR-204可能通过激活内质网应激介导的调亡途径诱导视网膜母细胞瘤细胞发生凋亡。     

唾液酸Lewis-X在慢性鼻-鼻窦炎鼻黏膜组织中的表达

目的:探讨唾液酸Lewis-X(SleX)在慢性鼻-鼻窦炎鼻黏膜组织中的表达.方法:利用SleX单克隆抗体,通过免疫组织化学技术对9例慢性鼻-鼻窦炎患者鼻黏膜组织及7例正常对照鼻黏膜组织进行染色,分析SleX在鼻黏膜组织中的表达.结果:SleX在鼻黏膜上皮细胞及中性粒细胞均有表达.SleX在慢性鼻-鼻窦炎鼻黏膜上皮细胞中的表达阳性率为88.9%,在正常鼻黏膜上皮细胞中的表达阳性率为14.3%,差异有统计学意义(P<0.05).结论:SleX在慢性鼻-鼻窦炎黏膜组织高表达,可能参与慢性鼻-鼻窦炎的发生.     

p-ERK2及ERK2在鼻息肉组织的表达及其意义

目的 检测磷酸化细胞外信号调节激酶2(p-ERK2)及细胞外信号调节激酶2(ERK2)在鼻息肉(NP)组织的定位及表达情况;初步探讨p-ERK2/ERK2在NP发病中的临床意义。 方法 应用间接免疫荧光技术(IIF)及蛋白免疫印记技术(WB)检测p-ERK2/ERK2在NP及正常鼻黏膜组织的定位及表达水平,并探讨其临床意义。 结果 NP:p-ERK2主要表达在增生的上皮细胞、炎症细胞以及腺上皮细胞,主要位于胞核;ERK2主要表达在腺上皮细胞、炎症细胞,主要位于胞质。正常鼻黏膜组织:p-ERK2主要表达在炎症细胞、腺上皮细胞,主要位于胞核;ERK2主要位于炎症细胞,主要位于胞质。荧光强度值:p-ERK2在NP和正常鼻黏膜组织的表达有统计学差异(P<0.05);ERK2在NP和正常鼻黏膜组织的表达无统计学差异(P>0.05)。WB灰度值:p-ERK2在NP和正常鼻黏膜组织的表达有统计学差异(P<0.05);ERK2在NP和正常鼻黏膜组织的表达无统计学差异(P>0.05)。 结论 p-ERK2在NP的发病机制中可能具有重要作用,而ERK2与NP的发生可能无关。ERK2在NP组及正常鼻黏膜组织均表达,提示ERK2可能参与鼻黏膜正常生理功能的维持。     

不伴有下气道疾病的慢性鼻-鼻窦炎患者肺功能及相关因素分析

目的 探讨不伴有下气道疾病的慢性鼻-鼻窦炎伴息肉患者的肺功能及其影响因素。 方法 选取161例慢性鼻-鼻窦炎伴鼻息肉患者(CRSwNP组),26例慢性鼻-鼻窦炎不伴鼻息肉患者(CRSsNP组)和34例正常人(对照组)进行肺功能检测,比较三组肺功能的各项指标,并分析CRSwNP组肺功能和临床各参数之间的关系,这些参数包括外周血嗜酸粒细胞数、血清特异性IgE、Lund-Mackay评分、呼出一氧化氮水平和视觉模拟量表评分(VAS)。 结果 CRSwNP组患者的肺功能指标FEV₁%pre低于正常组,差异有统计学意义(P=0.045);血清特异性IgE(sIgE)与VC%、FEV₁%pre、FEV₁/FVC呈负相关(P<0.05)。 结论 不伴下气道疾病的CRSwNP患者存在潜在的阻塞性肺功能改变;sIgE与CRSwNP的肺功能异常有关。     

ERK5蛋白在鼻息肉细胞中的表达和意义

目的 探讨细胞外调节蛋白激酶5(ERK5)在鼻息肉细胞中的表达和意义。 方法 分析2013年1月至2014年12月接受治疗的慢性鼻-鼻窦炎(CRS)患者的临床资料,将其中37例慢性鼻-鼻窦炎伴鼻息肉(CRSwNP)患者列为观察组(CRSwNP组),35例慢性鼻-鼻窦炎不伴鼻息肉(CRSsNP)患者作为对照组(CRSsNP组)。 结果 CRSwNP组患者血清中TNF-α(t=16.7,P<0.001)、IL-5(t=13.81,P<0.001)和IL-8(t=8.642,P<0.001)含量显著高于对照组,差异具有统计学意义(P>0.05);Western Boltting检测结果表明,在CRSwNP组中ERK5蛋白表达水平显著高于对照组中ERK5蛋白表达水平(灰度比1.21±0.16 vs 0.36±0.04,P<0.01,n=37);Pearson相关性检验分析结果表明,CRSwNP组患者ERK5蛋白表达与TNF-α(r=0.521,P=0.001)及IL-8(r=0.479,P=0.003)呈显著正相关。 结论 ERK5蛋白在CRSwNP患者中高水平表达,且与TNF-α及IL-8呈显著正相关关系。     

慢性鼻窦炎鼻息肉中转录因子NKX2-1调控嗜酸性炎症反应的作用

目的 研究新型转录因子NKX2-1在慢性鼻窦炎伴鼻息肉发病中调控嗜酸性免疫炎症反应的作用。 方法 功能性鼻内镜手术获取鼻息肉及非变应性单纯鼻中隔偏曲患者鼻甲标本,通过酶联免疫、免疫组化及蛋白印迹检测细胞因子IL-5、IFN-γ、IL-17A,转录因子NKX2-1及趋化因子CCL17在患者中的表达。 结果 鼻息肉患者中IL-5阳性表达率为24%,并伴有IL-4、IgE等炎症介质及酸性粒细胞浸润升高特征;40%鼻息肉患者关键细胞因子阴性表达并伴有IL-1β、IL-8等非嗜酸性炎症升高特征。单纯IL-5+鼻息肉患者NKX2-1表达低于非变应性单纯鼻中隔偏曲患者,单纯IL-5+鼻息肉患者中趋化因子CCL17高于非变应性单纯鼻中隔偏曲患者,且与趋化嗜酸性粒细胞相关。 结论 新型转录因子NKX2-1在不同内在型鼻息肉患者中具有表达差异,其在单纯IL-5+鼻息肉患者中表达下降且有负性调控嗜酸性炎症反应作用。     

短期布地奈德混悬液经鼻雾化对慢性鼻窦炎伴鼻息肉手术出血的影响

目的 评价短期应用布地奈德混悬液经鼻雾化对慢性鼻窦炎伴鼻息肉手术出血的影响。 方法 96例慢性鼻窦炎伴鼻息肉患者随机分成A组33例 、B组31例及C 组32例,A组术前7 d给予布地奈德混悬液经鼻雾化吸入及罗红霉素口服,B组给予布地奈德喷鼻剂喷鼻及罗红霉素口服,C组给予生理盐水鼻腔冲洗及罗红霉素口服。三组均在全麻气管插管下按统一方案手术。对比三组术中出血量及A、B组血清皮质醇浓度变化。 结果 A、B、C三组患者术中平均出血量分别为(51.70±18.62)mL、(73.16±19.23)mL、(90.16±15.97)mL,三组间差异有统计学意义(F=37.34, P<0.01)。A组用药后血清皮质醇浓度降低(P<0.01),但在正常值范围内;B组用药前后血清皮质醇浓度无变化(P>0.05)。 结论 短期应用布地奈德混悬液经鼻雾化吸入,可减少慢性鼻窦炎伴鼻息肉患者鼻内镜术中出血,且对肾上腺皮质功能无明显影响。     

Expression, localization, and significance of vascular permeability/vascular endothelial growth factor in nasal polyps

BACKGROUND: The exact etiologic mechanisms leading to the formation of nasal polyps have remained largely obscure. A key phenomenon of this specific type of chronic inflammatory disease in nasal respiratory mucosa is remarkable edema. Vascular permeability/vascular endothelial growth factor (VPF/VEGF) plays an important role in inducing angiogenesis and modulating capillary permeability. OBJECTIVE: To study the expression and localization of VPF/ VEGF as a putative key factor in nasal polyp development. METHODS: Specimens of nasal polyps (n = 12) were harvested during endonasal sinus surgery in patients with polypous chronic rhinosinusitis. Specimens of healthy nasal respiratory mucosa (n = 12) served as controls and were obtained from inferior turbinates of patients undergoing surgery for nasal obstruction without signs and symptoms of inflammatory disease. Frozen sections were immunohistochemically stained for VPF/VEGF and quantitatively analyzed, using computer-based image analysis. RESULTS: The expression of VPF/VEGF in specimens of nasal polyps was significantly stronger than in specimens of healthy nasal mucosa of controls. VPF/VEGF in polypous tissue was mainly localized in vascular endothelial cells, in basal membranes and perivascular spaces, and in epithelial cells. CONCLUSION: The markedly increased expression in nasal polyps as opposed to healthy nasal mucosa suggests that VPF/VEGF may play a significant role in both the formation of nasal polyps and in the induction of heavy tissue edema. This finding is discussed with respect to the differential expression of cyclooxygenase (COX) isoenzymes-1 and -2 (COX-1 and COX-2) in nasal polyps was significantly stronger than in specimens of healthy nasal mucosa of controls. VPF/VEGF in polypous tissue was mainly localized in vascular endothelial cells, in basal membranes and perivascular spaces, and in epithelial cells. Conclusion: The markedly increased expression in nasal polyps as opposed to healthy nasal mucosa suggests that VPF/VEGF may play a significant role in both the formation of nasal polyps and in the induction of heavy tissue edema. This finding is discussed with respect to the differential expression of cyclooxygenase (COX) isoenzymes-1 and -2 (COX-1 and COX-2) in nasal polyps.     

Increased expression of pendrin in eosinophilic chronic rhinosinusitis with nasal polyps

IntroductionChronic rhinosinusitis with nasal polyps is a heterogeneous disease and appropriate diagnostic algorithms in individual cases are necessary for effective medical treatment.ObjectiveThe purpose of this study was to clarify the relationship between the pendrin expression of nasal polyps and clinical and pathological characteristic features of eosinophilic chronic rhinosinusitis.MethodsA total of 68 patients were classified into eosinophilic chronic rhinosinusitis or non-eosinophilic chronic rhinosinusitis groups according to the degree of eosinophilic infiltration into the nasal polyps. Clinical, hematological, and immunohistochemical analyses were performed and statistically compared between both groups.ResultsThirty-eight were classified into eosinophilic chronic rhinosinusitis and 30 into non-eosinophilic chronic rhinosinusitis groups. There were no significant differences in age distribution, sex ratio, prevalence of asthma, or any other complications between the groups. The mean Lund–Mackay score and the number of serum eosinophils was significantly higher in the eosinophilic chronic rhinosinusitis than in the non-eosinophilic chronic rhinosinusitis groups. The pendrin expression was more frequently detected in the epithelial surface layer of nasal polyps in the eosinophilic chronic rhinosinusitis than in the non-eosinophilic chronic rhinosinusitis groups. In addition, mucin 5AC was more widely expressed in the eosinophilic chronic rhinosinusitis than in the non-eosinophilic chronic rhinosinusitis.ConclusionIncreased expression of pendrin and mucin 5AC in the nasal polyps would be associated with development of eosinophilic chronic rhinosinusitis. This finding could allow the development of a novel therapeutic agent targeted specifically to patients with eosinophilic chronic rhinosinusitis.     

转化生长因子β受体Ⅰ型及Ⅱ型在慢性鼻-鼻窦炎和鼻息肉组织中的表达

目的:探讨转化生长因子β受体(TGFβR)Ⅰ型及Ⅱ型在慢性鼻-鼻窦炎、鼻息肉及正常下鼻甲组织中表达的差异性,以及Ⅰ、Ⅱ型受体在慢性鼻窦炎、鼻息肉发病机制中可能的作用。方法:采用免疫组织化学方法检测TGFβRⅠ、TGFβRⅡ在25例慢性鼻-鼻窦炎、21例鼻息肉、17例下鼻甲组织中的表达,并比较TGFβRⅠ、TGFβRⅡ在慢性鼻-鼻窦炎、鼻息肉、正常下鼻甲组织中表达的差异。结果:TGFβRⅠ、TGFβRⅡ表达的平均灰度值在正常下鼻甲黏膜分别为175.78±7.06、165.00±1.79;在慢性鼻-鼻窦炎组织中分别为147.33±8.15、147.77±4.62;而在鼻息肉组织中分别为125.91±11.26、129.82±1.46。慢性鼻-鼻窦炎及鼻息肉组织中TGFβRⅠ、TGFβRⅡ的表达均比正常下鼻甲黏膜中的表达高,均差异有统计学意义(均P<0.01);且TGFβRⅠ、TGFβRⅡ在鼻息肉组织中的表达比在慢性鼻-鼻窦炎病变黏膜中的表达高,均差异有统计学意义(均P<0.01)。结论:TGFβRⅠ、TGFβRⅡ在慢性鼻-鼻窦炎、鼻息肉组织中具有不同的表达水平及分布特点,提示其可能在慢性鼻-鼻窦炎、鼻息肉的发生发展过程中发挥不同的作用。     

Macrolide treatment decreased the size of nasal polyps and IL-8 levels in nasal lavage

Recently, epidemiologic and experimental studies have been reported that long-term macrolides are effective for the treatment of chronic airway inflammatory diseases including diffuse panbronchiolitis, chronic rhinosinusitis, and cystic fibrosis (Jaffe A, Francis J, Rosenthal M, et al. Long-term azithromycin may improve lung function in children with cystic fibrosis. Lancet 351:420, 1998), and that macrolides can directly reduce the production of IL-8 by nasal epithelial cells (Suzuki H, Shimomura A, Ikeda K, et al. Inhibitory effect of macrolides on interleukin-8 secretion from cultured human nasal epithelial cells. Laryngoscope 107:1661-1666, 1997). In this study we administered macrolides with 14-membered rings to patients with nasal polyps due to chronic rhinosinusitis for at least 3 months and measured the IL-8 level in nasal lavage from those patients. The IL-8 levels in nasal lavage from patients with nasal polyps were reduced during macrolide treatment. There was significant correlation between decreased IL-8 levels in nasal lavage and the clinical effect of macrolides on the size of the nasal polyps. In the group whose polyps were reduced in size, the IL-8 levels dramatically decreased from 231.2 pg/mL to 44.0 pg/mL (p < 0.05), and were significantly higher before macrolide treatment than those in the group whose polyps showed no change (p < 0.005). This reduction in IL-8 may be an important aspect of the effect of macrolide treatment on nasal polyps in chronic rhinosinusitis.