免疫表型为弥漫大B细胞型的原发中枢神经系统淋巴瘤患者的预后分析

目的:对免疫表型为弥漫大B细胞型的原发中枢神经系统淋巴瘤(PCNSL)患者的预后因素进行分析探讨。方法:选取2011年3月至2017年10月徐州医科大学附属医院收治的免疫表型为弥漫大B细胞型的PCNSL患者42例,综合分析不同治疗方法对其总生存期的影响。结果:42例表型为弥漫大B细胞型PCNSL患者的性别、年龄、初诊脑脊液蛋白量及替莫唑胺、利妥昔单抗应用与否对患者总生存时间无影响(P>0.05),而尽早发现、及时治疗及治疗中常规鞘注、应用甲氨蝶呤能有效延长PCNSL患者总生存期。结论:尽早明确PCNSL诊断及积极规范化治疗能明显延长患者生存时间,同时进一步强调了常规鞘注对于延长患者生存期的必要性。     

颅内原发性中枢神经系统淋巴瘤的CT表现及回顾性分析

目的:研究颅内原发性中枢神经系统淋巴瘤(PCNSL)的CT表现特点。材料与方法:收集经病理证实的原发性中枢神经系统淋巴瘤7例,全部行CT平扫和增强检查。结果:7例患者2例多发,共检出10个病灶,其中肿块型6个,弥漫不规则型4个,具有一定的特征性表现。结论:通过回顾、分析,认为CT检查可进一步提高对颅内PCNSL的认识和诊断水平。     

原发性中枢神经系统淋巴瘤的发病特点和诊治分析

淋巴瘤是一类涉及到全身多个系统的肿瘤,原发性中枢神经系统淋巴瘤（primarycentralnervoussystemlymphoma,PCNSL）仍然是一种容易误诊的神经科疾病。早期的PCNSL可以没有任何症状和体征,严重的PCNSL可能引起精神智能障碍或危及生命。最近几年,我院通过手术和病理检查诊断了9例PCNSL,这些患者在术前均未能确诊。     

原发性中枢神经系统淋巴瘤的CT、MRI表现与病理对照研究

目的:探讨原发性中枢神经系统淋巴瘤(PCNSL)的CT、MRI表现。方法:选取18例于2013年4月至2014年4月期间我院接收的PCNSL患者,回顾性分析患者的CT、MRI及病理资料。结果:18例PCNSL中6例多发,12例单发,病灶共有32个,CT平扫中,8个病变表现为等或略高于脑组织密度影,MRI平扫,18个病变呈T2WI等或稍低信号,T1WI等低,在增强MRIT1WI图像上呈明显结节状或团块状均匀强化,发生在大脑半球的病灶中,可显示出"尖角征"、"缺口症";4例出现小囊变,其周围呈"硬环征"。结论:PCNSL影像学表现有一定特征,对临床诊断具有一定价值,但确诊有赖于病理检查。     

43例原发性中枢神经系统淋巴瘤的综合治疗

目的：研究原发性中枢神经系统淋巴瘤（PCNSL）的诊断及合理治疗方案。方法回顾性分析经术后病理证实的43例PCNSL患者的临床资料。结果 PCNSL以中老年人多见,临床表现复杂多样,病程短,病情进展快。MRI增强扫描病灶多呈均匀明显强化,可单发或多发。43例中单纯手术7例,术后全脑放疗15例,术后化疗11例,联合放化疗10例,联合治疗的患者中位生存期明显延长。结论 PCNSL临床表现无特征性,影像学特征不典型,病理诊断仍是确诊的金标准。PCNSL单纯手术治疗效果较差,采用包括手术和放化疗在内的综合治疗可提高疗效。     

脑脊液MyD88L265P基因突变对原发性中枢神经系统淋巴瘤预后的影响

目的:分析比较脑脊液髓样分化因子88L265P（MyD88L265P）突变和白细胞介素10（IL-10）与原发性中枢神经系统淋巴瘤（PCNSL）预后的关系。方法:收集2013年8月至2016年12月间复旦大学附属华山医院北院经手术或定位穿刺病理确诊的39例初发PCNSL患者（男18例,女21例,年龄40~73岁）的病例...     

MRI表现非典型的原发性中枢神经系统淋巴瘤三例

原发性中枢神经系统淋巴瘤(PCNSL)是少见的中枢神经系统肿瘤。少数PCNSL患者的临床症状及影像学表现与中枢神经系统炎症性脱髓鞘病变非常相似。该文报道MRI表现非典型的3例PCNSL患者,最初均被误诊为中枢神经系统炎症性脱髓鞘病变,首次经糖皮质激素治疗后病情均缓解,MRI显示病灶减少、缩小,但其后病情反复发作且加重,MRI显示病灶增多、增大,磁共振波谱均显示胆碱峰与氮-乙酰天门冬氨酸峰的比值大于2.0,最后均经脑病理活组织检查(活检)才确诊为PCNSL,化学治疗后病情均稳定。部分PCNSL患者因临床症状无特异性且MRI表现非典型,容易被误诊为炎症性脱髓鞘病变,延误了治疗,因此,临床上对于与该文报道的有相似表现的患者,应高度怀疑PCNSL,尽快行脑病理活检以助确诊,及时选择合适的治疗方案。     

中枢神经系统原发性淋巴瘤MR表现特点

目的 分析无免疫功能缺陷的原发性中枢神经系统淋巴瘤(primary central nervous system lymphomas PCNSL)患者12例,提高对该病MR诊断的准确率.方法 回顾性分析12例经手术或活检证实为PCNSL的MRI表现,其中男性7例、女性5例.共检出18个病灶,单发病例6例,多发病例(＞1个病灶)6例.病灶常位于大脑半球(n=6)、胼胝体(n=7)、基底节(n=2)及小脑半球(1).病灶MRI平扫表现T1低或等、T2低信号,DWI高信号;瘤周水肿及占位征象较轻,病灶内无出血、坏死、囊变及钙化等.结论 PCNSL为中枢神经系统少见肿瘤,其MRI平扫信号特点、强化方式、病灶分布可以为PCNSL的MR诊断提供十分重要的信息.     

大剂量甲氨蝶呤治疗原发性中枢神经系统淋巴瘤的观察与护理

目的 探讨大剂量甲氨蝶呤(HD-MTX)治疗原发性中枢神经系统淋巴瘤(PCNSL)的观察与护理方法。方法 选择2011年1月—2012年6月收治的PCNSL患者27例,通过心理护理、用药护理和不良反应护理协助其顺利完成HD-MTX治疗。结果 27例PCNSL患者共完成130次HD-MTX化疗,部分患者出现Ⅰ～Ⅱ度的骨髓抑制、黏膜溃疡和消化道毒性,均在对症处理后获得缓解。结论 HD-MTX是治疗PCNSL的重要措施,但不良反应常见,严重时可致死。有效的护理干预可减轻HD-MTX引起的毒副作用,帮助患者顺利度过化疗期,提高疗效,延长生存。     

放化疗联合治疗以发热为主要表现的中枢神经系统恶性淋巴瘤

原发性中枢神经系统淋巴瘤（primary central nervous system lymphoma,PCNSL）临床罕见,发生率占颅内肿瘤的1％左右,但以发热为主要症状的PCNSL国内外文献尚未见报道。PCNSL临床特征不明显,易误诊。对于PCNSL的早期诊断和治疗,尚无令人折服的方案。笔者首次应用放疗及大剂量甲氨喋呤（MTX）联合多药交替化疗,成功治疗以顽固发热为主要症状的PCNSL1例。现详细报道如下。     

结核性脑膜炎患者脑脊液中细胞因子水平的诊断价值

目的:探讨分泌性靶抗原-6(ESAT-6)、肿瘤坏死因子-α(TNF-α)、白细胞介素-10(IL-10)和干扰素-γ(IFN-γ)对于早期诊断结核性脑膜炎(TBM)的临床应用价值。方法:选取48例TBM患者为研究组,29例非结核性中枢神经系统感染患者为对照组,35例普通头痛患者为正常组。采用ELISA法分别检测所有患者脑脊液中的ESAT-6、IL-10、TNF-α和IFN-γ水平。结果:研究组的ESAT-6、TNF-α、IFN-γ水平与对照组相比增高,研究组与对照组的ESAT-6、IL-10、TNF-α、IFN-γ水平均高于正常组,差异均有统计学意义(P<0.05)。研究组的ESAT-6与IFN-γ水平呈正相关(r=0.96,P<0.05)。4项指标联合检测的灵敏度明显高于使用ESAT-6、IL-10、TNF-α、IFN-γ单一指标,差异均具有统计学意义(χ2=10.936,18.104,12.647,13.978;P<0.05)。结论:ESAT-6、TNF-α、IFN-γ和IL-10在TBM患者脑脊液中的表达水平显著升高,对早期诊断TBM具有重要的临床价值,而且4项联合检测较单一检测的诊断效果更佳。     

严重脓毒症患儿Toll样受体4水平及临床意义

目的 探讨Toll样受体4(TLR4)水平在严重脓毒症患儿中的临床意义.方法 采用前瞻性病例对照研究方法,选择儿科重症监护病房(ICU)住院且诊断符合严重脓毒症、脓毒性休克患儿14例(严重脓毒症组),以同期住院的支气管肺炎患儿(肺炎组)及健康体检儿童(健康对照组)各10例作为对照.取患儿入院时静脉血2 ml,用流式细胞仪检测TLR4水平,用酶联免疫吸附法(ELISA)测定血清白细胞介察(IL-6、IL-10)、肿瘤坏死因子-α(TNF-α)含量.结果 严重脓毒症组TLR4[(71.56±15.32)%]、IL-6[(1.98±1.55)ng/L]、IL-10[(88.20±61.23)ng/L]、TNF-α[(104.08±85.36)ng/L]水平均显著高于肺炎组[分别为(50.07±26.36)%、(0.93±0.16)ng/L、(41.42±7.02)ng/L、(48.96±6.40)ng/L]与健康对照组[分别为(39.43±17.43)%、(0.94±0.43)ng/L、(43.73±22.68)ng/L、(49.94±18.47)ng/L],差异均有统计学意义(均P＜0.05);而肺炎组与健康对照组间比较差异均无统计学意义(均P＞0.05).结论 TLR4是脓毒症发生与发展的启动点,其水平与促炎因子IL-6、TNF-α及抗炎因子IL-10水平一致;若将TLR4的变化与部分炎症介质水平相互结合,可作为脓毒症患儿早期诊断和病情严重程度的预测指标.     

危重病患者血中生长抑素水平检测的临床意义

目的 探讨危重病患者血中生长抑素(SST)水平与机体炎症反应和病情严重度的关系以及对预后的评估价值.方法 选择60例急性生理学与慢性健康状况评分系统Ⅱ(APACHE Ⅱ)评分≥8分的危重病患者,按照APACHE Ⅱ评分分为3组:轻度组(<16分)23例,中度组(16～20分)20例,重度组(>20分)17例;按预后分为死亡组(13例)与存活组(47例).另选择20例健康自愿者作为对照.用放射免疫法检测血中SST水平;用酶联免疫吸附法(ELISA)检测血中肿瘤坏死因子-α(TNF-α)、白细胞介索-6(IL-6)水平.结果 危重病组患者血中SST水平明显低于健康对照组[(18.2±17.6)ng/L比(224.8±130.2)ng/L,P<0.053;TNF-α、IL-6水平明显高于健康对照组[TNF-α:(32.4±14.2)ng/L比(14.2±5.7)ng/L,IL-6:(131.6±42.7)ng/L比(65.8±24.3)ng/L,P均<0.053;SST与TNF-α、IL-6水平均呈显著负相关(r1=-0.682,r2=-0.894,P均<0.01).重度组血中SST水平明显低于轻、中度组C(8.1±7.2)ng/L比(24.7±15.9)ng/L、(19.2±22.1)ng/L,P均<0.053;TNF-α、IL-6水平明显高于轻度组[TNF-α:(39.0±16.4)ng/L比(28.9±10.9)ng/L,IL-6:(156.05=49.6)ng/L比(111.5±32.6)ng/L,P均<0.053;SST水平与APACHE Ⅱ评分呈显著负相关(r=-0.327,P<0.05).死亡组血中SST水平明显低于存活组[(6.4±5.5)ng/L比(21.5±18.4)ng/L,P<0.053;TNF-α、lL-6水平虽高于存活组,但差异均无统计学意义.结论 危重病患者血中SST水平可以反映病情严重程度,对评估患者预后也具有临床价值.     

高浓度氧对未成年大鼠肺部炎症反应的影响

目的 探讨高浓度氧对未成年大鼠肺部炎症反应的影响.方法 将40只出生21 d的SD大鼠按随机数字表法分为空气对照组及高氧暴露12、24、48、72 h组,每组8只,分别将大鼠置于空气和常压高氧箱(氧含量达92%～94%)中.于相应时间点采用放血法处死大鼠后取肺组织,并行支气管肺泡灌洗.采用硫代巴比妥酸法和比色法分别测定肺组织丙二醛(MDA)含量及髓过氧化物酶(MPO)活性;采用酶联免疫吸附法(ELISA)检测支气管肺泡灌洗液(BALF)中肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和IL-10含量;观察肺组织病理改变,并进行肺损伤评分.结果 与空气对照组比较,高氧暴露12 h肺组织MDA含量(mmol/g)即显著升高(2.24±0.43比1.57±0.31),MPO活性(U/g)于高氧暴露24 h显著升高(1.24±0.25比0.69±0.22),并均随高氧暴露时间延长逐渐增加(P<0.05或P<0.01).BALF中TNF-α、IL-6和IL-10含量于高氧暴露24 h时较空气对照组显著增加[TNF-α(ng/L):135.2±44.0比94.5±22.3,IL-6(ng/L):73.1±14.2比55.7±17.3,IL-10(ng/L):67.9±21.7比48.2±7.6,P<0.05或P<0.01];但高氧暴露48 h时较24 h时显著降低(48 h时BALF中TNF-α、IL-6、IL-10分别为105.4±17.0,54.3±17.4,50.9±6.9,均P<0.05).高氧暴露12 h时肺损伤评分(分)即较空气对照组显著升高(4.5±1.4比1.3±0.5),并随高氧暴露时间延长进一步升高(P<0.05或P<0.01).结论 高浓度氧可引起未成年大鼠肺部炎症损伤;炎症细胞因子的出现高峰均在高氧暴露24 h.     

隐球菌性脑膜炎及病毒性脑炎患者脑脊液IL-6、IL-10和TNF-α含量检测及其临床意义

目的:探讨隐球菌性脑膜炎及病毒性脑炎患者脑脊液中白细胞介素-6(IL-6)、IL-10和肿瘤坏死因子-α(TNF-α)含量的变化及临床意义.方法:应用Luminex液相芯片技术对隐球菌性脑膜炎患者18例(隐脑组),病毒性脑炎患者20例(病脑组)及非中枢神经系统感染患者15例(对照组)脑脊液中IL-6、IL-10和TNF...     

高容量血液滤过对内毒素休克犬心肌组织Toll样受体4表达的影响

目的 探讨高容量血液滤过(HVHF)对内毒素休克心肌组织Toll样受体4(TLR4)mRNA表达的影响.方法 健康犬16只,静脉注射脂多糖(LPS)650 μg/kg诱导犬内毒素休克模型.将制摸成功的动物按随机数字表法分为对照组和HVHF治疗组,每组8只.用放射免疫法测定血中肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、IL-10含量,用逆转录-聚合酶链反应(RT-PCR)法测定心肌TLR4 mRNA表达,电镜下观察心肌组织病理改变.结果 治疗组HVHF后1、2、4 h血清TNF-α(μg/L:0.59±0.15、0.51±0.12、0.41±0.10)、IL-6(ng/L:11.08±2.83、9.82±2.58、8.25±2.05)、IL-10(μg/L:57.28±5.93、53.81±5.83、50.67±6.33)的含量显著低于本组成模时[(0.84±0.16)μg/L、(16.97±2.50)ng/L、(70.86±5.43)μg/L]和对照组相应时间点[TNF-α(μg/L):0.75±0.14、0.74±0.11、0.72±0.11,IL-6(ng/L):15.33±3.20、14.66±3.24、14.20±3.33,IL-10(μg/L):71.54±4.73、70.71±4.34、69.35±4.60],差异均有统计学意义(均P<0.01).治疗组较对照组心肌TLR4 mRNA表达明显下调(t=3.58,P<0.01).相关分析显示,TLR4 mRNA表达与循环血中TNF-α、IL-6、IL-10浓度呈正相关(r1=0.785,r2=0.569,r3=0.635,均P<0.05).电镜下观察治疗组心肌病理损伤较对照组减轻.结论 HVHF能下调内毒素诱导休克犬心肌TLR4mRNA 表达,减轻心肌炎症反应和心肌损伤.     

骨髓间充质干细胞对烟雾吸入性损伤兔早期炎症因子分泌的影响

目的 探讨骨髓间充质干细胞(MSCs)对烟雾吸入性损伤早期外周血及肺组织中肿瘤坏死因子-α(TNF-α)、白细胞介素(IL-1β、IL-6、IL-10)分泌的影响.方法 全骨髓培养法体外培养兔MSCs,用流式细胞术鉴定.将56只健康新西兰大耳白兔按随机数字表法分为正常对照组(C组,n=8)、烟雾吸入性损伤组(S组,n=24)、烟雾吸入性损伤+MSCs移植组(M组,n=24),后两组再分为伤后2、4、6 h亚组,每组8只.采用酶联免疫吸附法(ELISA)检测血浆及肺组织匀浆液中促炎因子TNF-α、IL-1β、IL-6及抗炎因子IL-10的含量.结果 与C组比较,S组各时间点血浆促炎、抗炎因子均显著升高;各时间点肺组织促炎因子显著升高,抗炎因子无明显变化.与S组比较,M组各时间点血浆促炎因子显著下降,抗炎因子显著升高[6 h时TNF-α(μg/L):1.7±1.7比4.1±1.6,IL-1β(ng/L):9.9±1.7比21.2±2.6,IL-6(μg/L):1.0±0.3比1.3±0.2,IL-10(ng/L):15.2±4.4比7.9±3.5,均P＜0.05];各时间点肺组织促炎因子显著降低,而抗炎因子仅在4 h、6 h显著升高[6 h时TNF-α(ng/L):503.0±156.4比587.7±171.2,IL-1β(ng/L):0.4±0.2比0.6±0.2,IL-6(ng/L):155.2±13.7比350.2±20.3,IL-10(ng/L):23.3±5.4比11.0±5.6,均P＜0.05].结论 MSCs移植能降低烟雾吸入性损伤早期促炎因子水平,升高抗炎因子水平,改善全身炎症反应,对烟雾吸入性损伤肺组织具有一定的保护作用.

Abstract：

Objective To explore the effect of bone marrow mesenchymal stem cells (MSCs) engraftment on secretion of tumor necrosis factor-α (TNF-α), interleukins (IL-1β, IL-6, IL-10) in peripheral blood and lung homogenates in the early stages of smoke inhalation injury. Methods MSCs were proliferated by the method of whole marrow culture and identified by flow cytometry. Fifty-six healthy New Zealand rabbits were randomly divided into control group (C group, n=8), smoke inhalation injury group (S group, n=24)and smoke inhalation injury+MSCs engraftment group (M group, n=24). The latter two groups were subdivided into 2, 4, 6 hours after injury subgroups, with 8 rabbits in each group. The levels of TNF-α,IL-1β, IL-6 and IL-10 in peripheral blood and lung homogenates were measured by enzyme-linked immunosorbent assay (ELISA). Results Compared with C group, concent of pro-inflammatory and anti-inflammatory cytokines in peripheral blood at each time point in S group were increased significantly.The concent of pro-inflammatory cytokines in lung homogenate at each time point in S group was significantly higher than thoae in C group, and that of anti-inflammatory cytokines showed no significant changes.Compared with the S group, concent of pro-inflammatory cytokines in peripheral blood in M group was decreased significantly, and that of anti-inflammatory cytokines was increased significantly [6 hours TNF-α(μg/L):1.7±1.7 vs. 4.1±1.6, IL-1β (ng/L): 9.9±1.7 vs. 21.2±2.6, IL-6 (μg/L): 1.0±0.3 vs.1.3 ± 0. 2, IL-10 (ng/L): 15. 2 ± 4. 4 vs. 7. 9 ± 3.5, all P＜0.05]. Concent of pro-inflammatory cytokines at each time point in M group was decreased significantly when compared with S group in lung homogenate,while only anti-inflammatory cytokine at 4 hours and 6 hours was increased significantly [6 hours TNF-α (ng/L): 503. 0±156. 4 vs. 587.7±171.2, IL-1β (ng/L): 0.4±0.2 vs. 0.6±0.2, IL-6 (ng/L): 155.2±13.7 vs. 350.2±20.3, IL-10 (ng/L): 23.3±5.4 vs. 11.0±5.6, all P＜0.05]. Conclusion MSCs engraftment could decrease pro-inflammatory cytokines and increase anti-inflammatory cytokines in the early stages of smoke inhalation injury, thus amelioratea inflammatory reaponse, which confers protective effect on smoke inhalation injury.     

白细胞介素-10和肿瘤坏死因子-α与高血压肾损害的相关性研究

目的 探讨肿瘤坏死因子-α(TNF-α)和白细胞介素-10(IL-10)在高血压肾损害患者中的变化及其相关性.方法 将73例原发性高血压患者(原发性高血压组)根据其尿蛋白排泄率不同又分为2个亚组:单纯高血压组37例,高血压肾损害组36例;采用放射免疫法检测血清TNF-α、IL-10浓度.同期选择30名健康体检者作为正常对照组.结果 原发性高血压组TNF-α高于正常对照组[(2.91±0.94)μg/L与(0.98±0.35)μg/L,P＜0.01],其中高血压肾损害组TNF-α高于单纯高血压组[(3.75±0.88)μg/L与(1.87±0.58)μg/L,P＜0.01].原发性高血压组IL-10低于正常对照组[(19.2±5.8)μg/L与(28.6±5.7)μg/L,P＜0.01],其中高血压肾损害组IL-10又低于单纯高血压组[(15.4±4.3)μg/L与(22.5±5.9)μg/L,P＜0.01].原发性高血压组TNF-α、IL-10与尿蛋白排泄率有相关性(r=0.703,P＜0.001 ;r=-0.613,P＜0.001),而与血压水平无相关性.结论 高血压肾损害患者TNF-α升高,IL-10水平降低,细胞因子系统的失衡可能参与了高血压肾损害的进展.

Abstract：

Objective To investigate the changes of the serum levels of necrosis alpha (TNF-o)and interleukin 10( IL-10 )in patients with hypertensive renal damage,and to study the correlation of TNF-α and IL-10 with the hypertensive renal damage. Methods Seventy three patients with primary hypertension were divided into two groups according to their urinary albumin excretion rate(UAER): simple hypertensive group( n = 37 ),hypertensive renal damage group(n =36). TNF-α and IL-10 were measured using radioimmune assay. Thirty normotensive healthy persons were selected as normotensive control group. Results TNF-α were significantly higher and IL-10 significantly lower in patients with essential hypertension than those in normotensive control group(TNF-α: [2.91 ±0.94]μg/L vs [0.98 ±0.35]μg/L,P＜0. 05;IL-10:[ 19.2 ±5.8]μg/L vs [28.6±5. 7] μg/L,P ＜0. 01 ) ,and in patients with hypertension,those with renal damage had higher TNF-α and lower IL-10 than those without( TNF-α: [ 3.75 ± 0. 88 ] μg/L vs [ 1.87 ± 0. 58 ] μg/L, P ＜ 0. 01; IL-10: [ 15. 4 ± 4. 3 ]μg/L vs [ 22. 5 ± 5.9 ] μg/L, P ＜ 0. 01 ), with statistically significant difference between groups ( P ＜ 0. 01 ).TN F-α and IL- 10 were found to have correlations with UAER ( r = 0. 703, P ＜ 0. 001; r = - 0. 613, P ＜ 0. 001 ),but no correlation with the level of blood pressure. Conclusion TNF-α increased and IL-10 decreased significantly in patients with hypertensive renal damage, which indicates that the imbalanced cytokine network may play a role in the pathological mechanisms of hypertensive renal damage.     

慢性血吸虫感染对脓毒症小鼠保护作用的研究

目的 初步探讨慢性血吸虫(SJ)感染对脓毒症小鼠的保护作用及其机制.方法 选择BALB/c雄性小鼠,按随机数字表法分组进行三部分实验.实验1:经腹部皮肤接种SJ尾蚴感染8周建立慢性SJ感染模型,分为正常组和SJ组,每组10只;用酶联免疫吸附法(ELISA)检测血清白细胞介素(IL-4和IL-10)、肿瘤坏死因子-α(TNF-α)、γ-干扰素(IFN-γ)水平,实时荧光定量聚合酶链反应(PCR)检测腹腔巨噬细胞IL-10和TNF-α的mRNA表达,了解慢性SJ感染小鼠免疫状态.实验2:以脂多糖(LPS)腹腔注射诱导小鼠脓毒症模型,分为LPS组和SJ-LPS组,每组15只;用ELISA法动态观察注射LPS后0、24、48和72 h细胞因子的变化,0 h的水平相当于正常小鼠和SJ感染8周水平,观察慢性SJ感染对脓毒症过程的影响.实验3:分别以盲肠结扎穿孔术(CLP)和LPS诱导两种不同的脓毒症模型,评价慢性SJ感染对脓毒症小鼠72 h存活率的影响.结果 实验1:SJ组血清抗炎因子IL-4[(151.35±12.24)ng/L]和IL-10[(133.22±11.09)ng/L]水平较正常组[IL-4(56.32±8.66)ng/L,IL-10(48.17±7.23)ng/L]显著升高(均P＜0.05),并可使巨噬细胞向替代活化性巨噬细胞分化,慢性SJ感染使腹腔巨噬细胞高表达IL-10 mRNA(SJ组4.46±1.82,正常组1.52±0.60),抑制TNF-α mRNA表达(SJ组1.61±0.93,正常组2.32±1.03,均P＜0.05).实验2、3:慢性SJ感染小鼠血清IL-4、IL-10于注射LPS后0 h即显著升高,随后下降,至72 h仍明显高于LPS组[IL-4(ng/L):92.2±7.6比41.5±4.5;IL-10(ng/L):92.1±7.8比35.6±4.0,均P＜0.05];TNF-α、IFN-γ均于24 h达峰值后逐渐下降,至72 h SJ-LPS组仍显著低于LPS组[TNF-α(ng/L):82.9±5.6比91.5±5.2;IFN-γ(ng/L):44.1±4.8比52.6±4.0,均P＜0.05].慢性SJ感染可明显改善CLP或LPS所致脓毒症小鼠的存活率(CLP:80%比20%,LPS:70%比30%,均P＜0.05).结论 慢性SJ感染可使脓毒症小鼠血清抗炎因子升高,存活率上升,从而起到保护作用.

Abstract：

Objective To preliminarily study the protective effect of chronic schistosoma japonica (SJ)infestation against sepsis in mice and its mechanism. Methods BALB/c male mice were used, and the experiment was divided into three parts. Experiment 1: chronic SJ infestation model was reproduced by SJ cercaria inoculation through abdominal skin for 8 weeks. Twenty mice were randomly grouped into normal group (n=10) and SJ group (n=10). The levels of interleukins (IL-4, IL-10), tumor necrosis factor-α(TNF-α) and interferon-γ (IFN-γ) in serum were detected by enzyme linked immunosorbent assay (ELISA).Real-time polymerase chain reaction (PCR) was employed to detect the levels of IL-10 mRNA and TNF-αmRNA in abdominal macrophages. This experiment was meant to evaluate immune state in mice with chronic SJ infestation. Experiment 2: lipopolysaccharide (LPS) was intraperitoneally injected to reproduce sepsis model. Thirty mice were randomly grouped into LPS group (n=15) and SJ-LPS group (n=15). The levels of cytokines were determined by ELISA at 0, 24, 48 and 72 hours after LPS injection. This experiment was meant to detect the effect of chronic SJ infestation in mice during the septic process. Experiment 3 : two types of sepsis model were reproduced by cecal ligation and puncture (CLP) and LPS injection, respectively. The survival rate of mice with chronic SJ infestation in 72 hours in either type of sepsis was evaluated. Results Experiment 1, compared with normal group [IL-4 (56.32±8.66) ng/L, IL-10 (48.17±7.23) ng/L],chronic SJ infestation showed an increase in serum IL-4 [(151. 35 ± 12. 24) ng/L] and IL-10 [(133. 22 ±11. 09) ng/L, both P＜0. 05]. Chronic SJ infestation also resulted in an increase in IL-10 mRNA expression (SJ group 4. 46±1. 82, normal group 1. 52±0. 60) and inhibited TNF-α mRNA expression (SJ group 1. 61±0.93, normal group 2. 32±1.03) in abdominal macrophages (both P＜0. 05), indicating that macrophages could be differentiated into alternative activated macrophages. Experiments 2 and 3 showed that the levels of serum IL-4 and IL-10 were increased at 0 hour after LPS injection, and then gradually decreased in SJ-LPS group, but the levels were still higher than those in LPS group at 72 hours [IL-4 (ng/L): 92. 2±7. 6 vs.41.5±4. 5; IL-10 (ng/L): 92. 1±7. 8 vs. 35. 6±4. 0, both P＜0. 05]; the levels of TNF-α and IFN-γ were increased at 24 hours, and then decreased in SJ-LPS group, and the levels were lower than those in LPSgroup at 72 hours [TNF-α (ng/L): 82. 9±5. 6 vs. 91. 5±5. 2; IFN-γ (ng/L): 44.1±4. 8 vs. 52. 6±4. 0,both P＜0. 05]. Therefore, chronic SJ infestation could improve the survival rate of mice with sepsis induced by CLP or LPS (CLP: 80% vs. 20%, LPS: 70% vs. 30%, both P＜0.05). Conclusion Chronic SJ infestation could elevate anti-inflammatory factors in septic mice, thus ameliorating the survival rate, so it has protective effect on mice with sepsis.