IL-23/IL-17轴在脓毒症中的表达及意义

目的:探讨IL-23/IL-17轴在脓毒症患者中的表达及意义.方法:符合诊断标准的脓毒症患者40例,以28天预后为终点,将患者分为存活组(n=21)和病死组(n=19),分析各组病人的急性生理和慢性健康评分(APACHE)Ⅱ和序贯器官衰竭估计(SOFA)评分,同时在入ICU第1天采取外周静脉血做IL-23和IL-17检测,并对病死率和IL-23、IL-17、APACHEⅡ、SOFA做相关性分析.结果:与存活组比较,病死组患者拥有较高的APACHEⅡ和SOFA评分(P<0.01),且外周血的IL-23和IL-17蛋白含量均明显升高(P<0.05).APACHEⅡ和SOFA评分、IL-17和IL-23含量与28天预后有明显的相关性(P<0.05).结论:脓毒症Th17细胞分泌的IL-23/IL-17增加,加重患者病情,在脓毒症发病机制中可能扮演重要角色.     

致病性Th17细胞在神经炎症中的作用及调控机制的研究进展

神经炎症是中枢神经系统在损伤、感染、毒素等各种影响内稳态因素的刺激下产生的复杂免疫反应,涉及驻留在中枢神经系统中的多种免疫细胞.持续存在的神经炎症是所有神经系统疾病(包括神经发育、神经退行性和精神性疾病)病因和病程的共同特性.Th17细胞是CD4+T细胞的一个重要亚型,在稳态条件下介导对细胞外细菌和真菌的免疫反应,维持...     

退变腰椎间盘组织细胞凋亡相关蛋白酶Caspase-10 的表达研究

目的:探讨凋亡相关蛋白酶Caspase-10在腰椎间盘退变中的表达。方法:45例腰椎间盘突出症病人按年龄分为青年、中年和老年患者组,5例青少年型特发性脊柱侧弯病人作为对照组。患者组标本均为术中所取出L4/5新鲜椎间盘髓核组织,对照组标本均为术中所取出L2/3新鲜椎间盘髓核组织。采用TUNEL法和免疫组织化学S-P法,分别检测腰椎间盘髓核中的凋亡阳性细胞率及Caspase-10的表达情况。结果:对照组髓核内TUNEL阳性细胞率为(17.80±0.62)%。青年、中年、老年患者组髓核内TUNEL阳性细胞率分别为(45.71±2.05)%、(53.65±2.93)%和(68.39±4.33)%。四个组两两之间差异均有统计学意义(P<0.05)。对照组髓核内Caspase-10染色阳性细胞率为(32.60士1.64)%。青年、中年、老年患者组髓核内Caspase-10染色阳性细胞率分别为(50.67士2.89)%、(63.12士4.61)%和(75.28士4.26)%。四个组两两之间差异均有统计学意义(P<0.05)。髓核内Caspase-10染色阳性细胞率与TUNEL阳性细胞率和年龄之间均呈正相关(P<0.01)。结论:退行性变腰椎间盘组织中凋亡细胞率以及Caspase-10的表达均高于正常椎间盘组织,年龄是细胞凋亡的重要影响因素,细胞凋亡以及Caspase-10的表达上调可能在腰椎间盘退行性变的发生和发展中发挥重要作用。     

Th17细胞的分化、调节及其主要细胞因子和功能

近几年来以分泌白介素17(interleukin 17,IL-17)为特征的辅助性T细胞Th17(T help cell 17,Th17)细胞被认为是有区别于Th1(T help cell 1,Th1)、Th2(T help cell 2,Th2)新型的细胞亚群,它的发现改变了以往人们只将Th细胞分为Th1、Th2的传统分类认识。Th17细胞参与了自身免疫疾病、肿瘤的发生及机体各种炎症的发病机制,其分泌的细胞因子在生物学功能中发挥了极其重要的作用。同时Th17细胞的活化需要各种转化生长因子、IL-6(interleukin 6,IL-6)、IL-23(interleukin 23,IL-23)等细胞因子的参与,活化的Th17细胞同时再进一步的促进各种细胞因子的分泌,以通过分泌IL-17、IL-21(interleukin 21,IL-21)、IL-22(interleukin22,IL-22)、IL-26(interleukin 26,IL-26)、肿瘤坏死因子(tumor necrosis factor,TNF)α等细胞因子导致机体炎症等各种疾病的发生。     

Th 细胞因子IL-17、IFN-γ、IL-4 在狼疮性肾炎中的表达及意义

目的:探讨T辅助细胞(Th)相关细胞因子在狼疮性肾炎发病中的免疫机制作用。方法:64例系统性红斑狼疮患者和28例健康体检者作为对照,采用酶联免疫吸附测定法(ELISA法)检测所有受试者血清IL-17、IFN-γ、IL-4水平,并对其与SLEDAI、SDI、24小时尿蛋白量相关性进行研究。结果:狼疮性肾炎组血清IL-17水平显著高于狼疮无肾炎组和健康对照组(P<0.001),狼疮性肾炎组血清IFN-γ水平显著高于狼疮无肾炎组(P<0.05)和健康对照组(P<0.01),血清IL-4水平在狼疮性肾炎组、狼疮无肾炎组均显著高于健康对照组(P<0.01)。狼疮性肾炎组IFN-γ/IL-4比值显著高于狼疮无肾炎组(P<0.01)和健康对照组(P<0.05);狼疮无肾炎组IFN-γ/IL-4比值显著低于健康对照组(P<0.01)。SLE患者血清IFN-γ表达水平与SLEDAI积分呈正相关(r=0.402,P<0.05),血清IL-17、IL-4表达水平与SLEDAI、SDI、抗ds-DNA抗体、C3、24小时尿蛋白量均无相关性。结论:狼疮性肾炎患者外周血中IL-17、IFN-γ、IL-4等促炎细胞因子均有不同程度升高促起炎症发生及组织损伤,参与了狼疮性肾炎的免疫发病过程。     

靶定IL-17 治疗类风湿关节炎研究进展

IL-17作为前炎症因子参与类风湿关节炎,系统性红斑狼疮等自身免疫性疾病的病理过程。它主要由CD4+T细胞的一个亚群--Th17细胞分泌释放。目前,IL-17在类风湿关节炎的病理过程中的作用引起了医学界广泛的关注,抗IL-17A抗体已经生产并进入临床实验,用于治疗类风湿关节炎、银屑病关节炎等疾病。但其在类风湿关节炎病理过程中的作用尚需进一步研究,其有效性亦尚需进一步探讨。本文主要针对IL-17家族的各个亚型的表达、调控、生物学作用及与类风湿关节炎发病的关系进行阐述,为类风湿关节炎的治疗提供新的思路。     

Peroxiredoxin Ⅱ在退变椎间盘髓核中的表达及其临床意义

目的:检测PeroxiredoxinⅡ在腰椎间盘髓核组织中的表达,分析其在椎间盘退变中的临床意义。方法:用蛋白免疫印迹(Western blot)的方法检测PeroxiredoxinⅡ在正常、突出及脱出腰椎间盘髓核中的表达情况。结果:PeroxiredoxinⅡ在退变椎间盘髓核中表达丰富,而在正常椎间盘髓核中表达微弱,两者比较差异显著(P<0.05),在突出和脱出椎间盘髓核中表达无显著性差异(P>0.05)。结论:PeroxiredoxinⅡ在正常及退变腰椎间盘髓核组织中差异表达。     

PeroxiredoxinⅡ在退变椎间盘髓核中的表达及其临床意义

目的：检测PeroxiredoxinⅡ在腰椎间盘髓核组织中的表达,分析其在椎间盘退变中的临床意义。方法：用蛋白免疫印迹（Western blot）的方法检测PeroxiredoxinⅡ在正常、突出及脱出腰椎间盘髓核中的表达情况。结果：PeroxiredoxinⅡ在退变椎间盘髓核中表达丰富,而在正常椎间盘髓核中表达微弱,两者比较差异显著（P〈0.05）,在突出和脱出椎间盘髓核中表达无显著性差异（P〉0.05）。结论：PeroxiredoxinⅡ在正常及退变腰椎间盘髓核组织中差异表达。     

TH17细胞相关细胞因子IL-17和IL-23在系统性红斑狼疮中的表达及其意义

目的:探究SLE的发病机制,通过测定SLE患者及正常人外周血浆中的IL-17以及IL-23的表达水平,研究SLE患者体内的IL-17以及IL-23水平是否异常,并探讨其在SLE疾病中的作用.通过研究有望为SLE患者的治疗在细胞因子方面提供方向.方法:SLE组33例;健康对照组20例.采用酶联免疫吸附试验测定血浆中IL-17、IL-23的水平,收集整理SLE患者的临床资料及实验室数据.按照SLE患者疾病活动度、有无狼疮肾炎和抗ds-DNA阳性与否以及补体水平进行分组.结果:活动期SLE患者血浆中的IL-17以及IL-23水平明显高于对照组(P＜0.01),与SLE非活动组相比,也有明显差异,其具有统计学意义(P＜0.01),但非活动组与正常对照组间无统计学意义.狼疮肾炎组和非狼疮肾炎组患者血浆中的IL-17和IL-23水平均高于正常对照组(P＜0.01),但IL-17和IL-23的水平在肾炎组和非肾炎组间无明显统计学差异.抗ds-DNA抗体阳性组与阴性组间IL-17和IL-23水平也无明显统计学差异.补体C3、C4水平高值组与正常组间IL-17和IL-23水平也无明显统计学差异.结论:IL-17和IL-23表达水平在SLE患者活动期血浆中表达有明显增高,提示IL-17和IL-23可能参与了SLE疾病的发生发展过程,可能与疾病的活动度有密切的关系.是否有肾脏损害以及抗ds-DNA抗体阳性与否、补体水平的高低与否可能对SLE患者血浆中IL-17和IL-23的表达水平影响较小.通过此研究我们可以在SLE的细胞因子治疗方面有进一步突破,进一步明确SLE的发病机制,为SLE患者带来更大的福音.     

IL-23/Th17轴在变应性哮喘中的研究进展

变应性哮喘是一种由辅助性T细胞（T helper cell,Th cell）调节的慢性炎症性疾病。Th1/Th2的失衡一直被认为是变应性哮喘的发病机制,Th2细胞及其分泌的细胞因子白介素4（interleukin 4,IL-4）、IL-5以及IL-13在变应性哮喘特异性症状的发病中发挥重要作用。最近研究发现Th17细胞及其分泌的IL-17参与变应性哮喘的发展过程,IL-23在Th17细胞维持生存和功能成熟中发挥重要作用,并参与抗原诱导的气道炎症反应。该文对目前IL-23/Th17轴在变应性气道炎症反应中的研究进展作一综述。     

一种新型大鼠腰椎间盘突出症动物模型的建立

目的建立一种大鼠腰椎间盘突出症的动物模型。方法采用自体髓核移植至背根神经节＋铬制肠线环扎神经根的方法,建立根性神经痛模型,观察背根神经节的组织学改变及超微结构改变,用Von Frey针丝和RTX-1型热痛测试仪检测动物的痛觉行为改变。结果该方法可诱导出明显的机械刺激痛觉超敏与热刺激痛觉过敏,术后1周时最为明显,术后3周时仍有较明显的神经行为异常;术后1周时背根节出现明显的充血水肿,而术后3周以脱髓样改变和纤维细胞增生为主。结论自体髓核移植＋铬制肠线环扎神经根可较好地引起根性神经痛的发生,可作为研究椎间盘突出症的动物模型。     

MRI Assessment of Lumbar Intervertebral Disc Degeneration with Lumbar Degenerative Disease Using the Pfirrmann Grading Systems

Background

To evaluate by MRI intervertebral disc degeneration in patients with lumbar degenerative disease using the Pfirrmann grading system and to determine whether Modic changes correlated with the Pfirrmann grades and modified Pfirrmann grades of disc degeneration.

Methods

The clinical data of 108 surgical patients with lumbar degenerative disease were reviewed and their preoperative MR images were analyzed. Disc degeneration was evaluated using the Pfirrmann grading system. Patients were followed up and low back pain was evaluated using the visual analog scale (VAS) and the effect of back pain on the daily quality of life was assessed using Oswestry disability index (ODI).

Results

Forty-four cases had normal anatomical appearance (Modic type 0) and their Pfirrmann grades were 3.77±0.480 and their modified Pfirrmann grades were of 5.81±1.006. Twenty-seven cases had Modic type I changes and their Pfirrmann grades were 4.79±0.557 and their modified Pfirrmann grades were 7.00±0.832. Thirty-six cases exhibited Modic type II changes and their Pfirrmann grades and modified Pfirrmann grades were 4.11±0.398 and 6.64±0.867, respectively. One case had Modic type III changes. Kruskal-Wallis test revealed significant difference in modified Pfirrmann grade among Modic type 0, I and II changes (P<0.01) but no significant difference between Modic type I and II changes (P>0.05). Binary regression analysis showed that Modic changes correlated most strongly with disc degeneration. Follow up studies indicated that the VAS and ODI scores were markedly improved postoperatively. However, no difference was noted in VAS and ODI scores among patients with different Modic types.

Conclusion

Modic changes correlate with the Pfirrmann and modified Pfirrmann grades of disc degeneration in lumbar degenerative disease. There is no significant correlation between Modic types and surgical outcomes.     

真核表达猪白细胞介素17及其生物活性研究

目的:为真核表达猪白细胞介素17(IL-17),研究产物在细胞培养下的免疫生物活性。方法:通过PCR扩增出猪IL-17基因并插入到真核表达载体p VAX1,然后转染到IPEC-J2细胞、Ha Ca T细胞和L02细胞中。在转染后第24、48和72h收集细胞,第48h收集上清液。收集细胞通过实时荧光定量PCR检测相关免疫基因的表达水平,收集上清液通过抑菌试验检测相关抗菌肽的生物活性。结果:采用p VAX1载体构建了表达猪IL-17的重组质粒,转染到细胞中。证实IL-17基因能诱导抗菌肽基因(RegⅢ、S100A8和BD2)的表达,显著上调JAK-STAT信号通路基因(JAK1、STAT1和STAT3)和细胞因子基因(IL-6、IL-12和TNF-α)的表达。此外,细胞上清液能够在不同程度上抑制大肠杆菌及金黄色葡萄球菌的增殖。结论:成功将猪IL-17基因真核表达,其表达产物能诱导效应细胞表达多种细胞因子,产生多种抗菌肽,具有抑菌能力;这为进一步研发猪IL-17作为抗菌免疫分子制剂奠定了初步基础。     

代谢综合症患者血清IL-18 水平变化及临床意义

目的:研究血清IL-18与亚代谢综合症(亚MS)、代谢综合症(MS)的关系,探讨生活方式改变(TLC)后IL-18及相关标记物的变化及其临床意义。方法:16例对照组,14例亚MS组,34例MS组;采用自动生化仪测定空腹血脂水平;采用乳胶增强免疫比浊法检测hs-CRP水平;采用ELISA法检测受试者血清IL-18、IL-6和脂联素水平。结果:MS患者血清IL-18水平与腰围有明显相关性(rs=0.45,P<0.01);与亚MS组比较,MS组IL-18水平显著升高(P<0.01);与正常组比较,MS组患者的腰围、体重指数、hs-CRP、IL-6及IL-18显著升高(P<0.05)。TLC后体重减轻5%,MS患者IL-18、IL-6、hs-CRP水平显著降低(P<0.01),脂联素水平显著升高(P<0.01)。结论:IL-18可作为亚MS和MS预测指标,鉴别亚MS与MS,其含量的变化对病情进展的程度及疗效的判定有重要意义。     

IL-17A Induces Pendrin Expression and Chloride-Bicarbonate Exchange in Human Bronchial Epithelial Cells

The epithelium plays an active role in the response to inhaled pathogens in part by responding to signals from the immune system. Epithelial responses may include changes in chemokine expression, increased mucin production and antimicrobial peptide secretion, and changes in ion transport. We previously demonstrated that interleukin-17A (IL-17A), which is critical for lung host defense against extracellular bacteria, significantly raised airway surface pH in vitro, a finding that is common to a number of inflammatory diseases. Using microarray analysis of normal human bronchial epithelial (HBE) cells treated with IL-17A, we identified the electroneutral chloride-bicarbonate exchanger Pendrin (SLC26A4) as a potential mediator of this effect. These data were verified by real-time, quantitative PCR that demonstrated a time-dependent increase in Pendrin mRNA expression in HBE cells treated with IL-17A up to 48 h. Using immunoblotting and immunofluorescence, we confirmed that Pendrin protein expression is increased in IL-17 treated HBE cells and that it is primarily localized to the mucosal surface of the cells. Functional studies using live-cell fluorescence to measure intracellular pH demonstrated that IL-17A induced chloride-bicarbonate exchange in HBE cells that was not present in the absence of IL-17A. Furthermore, HBE cells treated with short interfering RNA against Pendrin showed substantially reduced chloride-bicarbonate exchange. These data suggest that Pendrin is part of IL-17A-dependent epithelial changes and that Pendrin may therefore be a therapeutic target in IL-17A-dependent lung disease.     

椎间孔镜与开窗术对腰椎间盘突出患者远期治疗效果对比

目的:探究椎间孔镜与开窗术对腰椎间盘突出患者治疗远期效果对比。方法:选择2016年3月至2018年3月于我院接受治疗的腰椎间盘突出患者,按照其接受术式的不同将其分为孔镜组(108例)和开窗组(40例),对比两组手术出血量、术后卧床时间及切口长度,对比两组术前、术后3个月及术后12个月腰椎日本矫形外科学会(Japan Orthopaedic Assoctiation,JOA)评分、Odwestry功能障碍指数(Odwestris ability index, ODI)评分、视觉模拟评分(Visual analog scales,VAS)及生活质量评分,最后对比两组术后12个月椎间隙高度降低数值。结果:(1)孔镜组术中出血量、术后卧床时间及切口长度均小于开窗组,手术时间长于开窗组(P0.05);(2)术前两者JOA及ODI评分对比无统计学意义(P0.05),术后3个月及术后12个月孔镜组JOA及ODI评分优于开窗组(P0.05);(3)术前两组VAS及SF-36量表(the 36-item shot form health survey,SF-36)评分对比无统计学意义(P0.05),术后3个月及12个月两组VAS评分均有明显下降,SF-36评分有明显上升(P0.05),且术后3个月及12个月孔镜组SF-36评分高于开窗组(P0.05),VAS评分对比无统计学意义(P0.05);(4)术后12个月,孔镜组椎间隙高度降低率低于开窗组(P0.05)。结论:椎间孔镜在治疗腰椎间盘突出方面效果较好,相比于开窗术,孔镜术患者术中创伤小、术后恢复快、腰椎功能改善明显,且远期随访显示患者生活质量更高,值得进行临床推广。     

Transient Calretinin Expression during Intervertebral Disc Formation of the Chick Embryo

Calretinin immunoreactivity was localized during chick embryonic cervical spine development from day 4 until day 16. A transitory expression of calretinin could be seen from embryonic day 5 to embryonic day 15 in the mesenchymal cells forming the intervertebral disc. Calretinin was most abundant at embryonic day 8 when a maximal proliferation of cells occurred.
At embryonic day 12, calretinin positive fibroblasts were located along the fibers forming the annulus fibrosus. At embryonic day 16, calretinin immunoreactivity could no more be detected in the cervical column. In conclusion, an intracellular calcium binding proteins belonging to the calmodulin/troponin C superfamily, appeared to be a marker for the disc formation.     

The Role of Human IL-17 Immunity in Fungal Disease

Candida species are major causes of invasive and mucocutaneous fungal infections. Various recognition pathways and effector mechanisms are involved in triggering intrinsic, innate and adaptive host immune responses to these fungi. Invasive candidiasis may involve almost any internal organ or anatomic site and is a significant cause of morbidity and mortality in immunocompromised individuals, including, in particular, those with primary immunodeficiency disorders (PIDs) affecting phagocytic cells. Other PIDs characterized by an impairment of IL-17 T cell-mediated immunity confer predisposition to mucocutaneous Candida infections, with Candida albicans in particular. We discuss here inborn errors of immunity leading to an impairment of IL-17-mediated host defense and the occurrence of mucocutaneous candidiasis.