化瘀解毒法对溃疡性结肠炎大鼠血清IL-4和IL-10水平的影响

目的 探讨化瘀解毒中药防治溃疡性结肠炎的作用机理.方法 将40只Wistar大鼠随机分为正常组、空白对照组、中药组和柳氮磺吡啶组,每组10只.应用2,4,6-三硝基苯磺酸(TNBS)复制溃疡性结肠炎动物模型,中药组给予化瘀解毒中药汤剂灌胃,柳氮磺吡啶组给予柳氮磺吡啶灌胃,正常组及空白对照组灌服等体积蒸馏水.21 d后观察大鼠结肠大体形态学及组织病理学改变,采用ELISA法检测各组大鼠的血清IL-4和IL-10水平.结果 化瘀解毒中药能有效提高溃疡性结肠炎大鼠血清IL-4和IL-10水平,并对损伤的大肠黏膜有明显修复作用.结论 化瘀解毒中药能够促进抗炎因子IL-4和IL-10的产生和表达,并对大鼠实验性溃疡性结肠炎疗效显著,说明该法对血清IL-4和IL-10的调节作用可能是其治疗机制之一.     

溃肠宁对TNBS模型大鼠肠形态、血清及结肠组织IL-6和IL-10影响的观察

[目的]观察中药溃肠宁对三硝基苯磺酸（TNBS）致溃疡性结肠炎（UC）大鼠模型肠黏膜形态、大鼠血清及结肠黏膜组织中白介素-6（IL-6）、白介素-10（IL-10）表达的影响,探讨溃肠宁抗UC的相关作用机制以及疗效.[方法]采用TNBS复合50％乙醇法复制UC大鼠模型,分别采用中药溃肠宁和柳氮磺胺毗啶（SASP）作为阳性对照组进行治疗,对比模型组和空白对照组采用ELISA法对各组大鼠肠血清以及肠黏膜中IL-6、IL-10进行检测,并对其检测结果进行分析.[结果]模型组大鼠结肠和血清中的IL-6含量明显高于正常组（P＜0.01）,IL-10的含量则明显低于正常组（P＜0.01）;SASP组结肠及血清中IL-6、IL-10含量与模型组比较差异有统计学意义（P＜0.01）;中药组和模型组相比,结肠和血清中IL-6含量明显低于模型组（P＜0.01）,IL-10的含量则明显高于模型组（P＜0.01）;中药组与西药SASP组比较,中药组结肠和血清中IL-6含量低于西药组,IL-10的含量高于西药组,可见2组之间差异有统计学意义（P＜0.01）.[结论]溃肠宁对TNBS复合50％乙醇法UC大鼠疗效显著,其作用机制可能与调节机体的免疫有关.     

苦豆子总碱对大鼠溃疡性结肠炎细胞因子IL-10表达的影响

目的观察苦豆子总碱对大鼠溃疡性结肠炎(UC)的外周血和结肠组织中IL-10表达的影响。方法将SD大鼠随机分成6组(正常组、模型组、柳氮磺胺吡啶(SASP)、苦豆子总碱高剂量组、中剂量组、低剂量组),采用三硝基苯磺酸(TNBS)灌肠法,制备结肠炎大鼠模型。第2天开始灌胃,在第3周杀鼠后用酶联免疫吸附法(ELISA)检测IL-10在结肠黏膜组织和外周血清中的表达水平;同时分析结肠黏膜组织IL-10与DAI(疾病活动指数评分)/组织学损伤的相关性。结果(1)结肠部位和外周血清中IL-10的表达较对照组均显著降低,其中以结肠部位降低的幅度最大(P<0.01)。(2)苦豆子总碱高、中、低3个剂量组和SASP组都能显著性上调结肠部位和外周血清的IL-10的表达(P<0.05),且结肠部位的变化与外周血的相比差异明显。(3)结肠部位的DAI与结肠IL-10之间存在的负相关性(Pearsonr=-0.828,P<0.01),结肠部位的组织学损伤与结肠IL-10之间存在负相关性(Pearsonr=-0.819,P<0.01);所有检测为双侧,样本容量n=60。结论苦豆子总碱通过上调IL-10的表达减轻或改善实验性结肠炎大鼠的组织学损伤和症状。     

IL-17、IL-23、IL-6、TGF-β1和Foxp3在实验性结肠炎中的表达

目的 观察2、4、6-三硝基苯磺酸(TNBS)诱导的大鼠结肠炎模型中结肠Foxp3、TGF-β1的表达及外周血清IL-17、IL-23和IL-6的表达,以探讨Th17细胞在IBD的作用.方法 10只SD大鼠以三硝基苯磺酸(TNBS)/L醇溶液灌肠诱导结肠炎模型.另取10只大鼠作为正常对照组(0.9%NaCl溶液灌肠).干预2周后行结肠大体损伤指数(CMDI)和组织学损伤指数(TDI)评分,以酶联免疫吸附测定(ELISA)检测血清白介素-6(Interteukin 6,IL-6)、IL-17和IL-23水平,以免疫组化方法(SP法)检测结肠组织转化生长因子-β1(TGF-β1)和叉头样转录因子-3(Foxp3)表达.结果 与正常组相比,结肠炎模型组CMDI和TDI显著升高(P<0.01),血清IL-6、IL-17和IL-23水平明显升高(P<0.05),结肠组织TGF-β1和Foxp3明显降低(P<0.05).结论 在TNBS诱导的大鼠实验性结肠炎中,IL-6可能通过介导T细胞向Th17或Treg细胞的分化,促进或抑制肠道炎症.     

定喘止哮颗粒对支气管哮喘动物模型血清IFN-γ、IL-4、IL-5的影响

目的研究定喘止哮颗粒对支气管哮喘动物模型血清干扰素(IFN)-γ、白细胞介素(IL)-4、IL-5的影响。方法通过10%卵蛋白肌肉注射、超声雾化吸入致敏建立支气管哮喘大鼠模型。分为对照组,模型组,阳性对照药氨茶碱0.025 g/kg组,定喘止哮颗粒4、2、1 g/kg三个剂量组。观察各组动物血液中IL-4、IL-5、IFN-γ含量变化情况。结果定喘止哮颗粒4、2 g/kg两个剂量组均能明显抑制豚鼠血清中增高的IL-4、IL-5含量;4 g/kg剂量组能明显升高豚鼠血清中减低的INF-γ含量,与模型组比较差异显著(P<0.05或P<0.01)。结论定喘止哮颗粒可以使INF-γ水平明显升高,IL-4、IL-5水平明显降低,可能通过调节Th1/Th2细胞之间功能平衡,从而达到减轻气道炎症反应的作用。     

脾肾阳虚型溃疡性结肠炎大鼠模型的研制

[目的]采用复合多因素法研究制造切实可行并符合中医证候特点的脾肾阳虚型溃疡性结肠炎(ulcerative colitis,UC)大鼠模型。[方法]40只雄性SD大鼠随机分为:正常对照组、溃疡性结肠炎模型组(简称溃结组)、脾肾阳虚模型组(简称脾肾阳虚组)、脾肾阳虚型溃疡性结肠炎模型组(简称病证模型组)。正常对照组给予普通喂养;溃结组采用三硝基苯磺酸(TNBS)与乙醇复合物诱导灌肠进行造模;脾肾阳虚组给予番泻叶、腺嘌呤分阶段灌胃结合外因干预处理;病证模型组给予番泻叶、腺嘌呤分阶段灌胃结合外因干预并TNBS与乙醇复合物诱导灌肠进行造模。观察各组大鼠症状、体征及结肠病理改变,并检测血清中白介素6(IL-6)、白介素8(IL-8)、肿瘤坏死因子(TNF-α)、游离三碘甲腺原氨酸(FT3)、游离甲状腺素(FT4)、睾丸酮(T)、皮质醇(Cor)及D-木糖的浓度。[结果]病证模型组大鼠出现嗜睡懒动,反应迟钝,蜷卧扎堆,毛发疏松粗糙、晦暗无光泽,眯眼弓背,肛周污秽,便形稀溏甚则黏液血便等症状;大鼠体重明显减轻,饮水量明显减少,肛温下降,与正常对照组比较差异有统计学意义(P<0.05);显微镜下观察结肠黏膜呈缺损及坏死脱落,形成溃疡灶,局部充血、水肿明显,伴大量炎细胞浸润;大鼠结肠组织损伤程度评分及血清中IL-6、IL-8、TNF-α、FT3、FT4、T、Cor及D-木糖的浓度与其他各组比较,差异有统计学意义(P<0.05)。[结论]通过番泻叶、腺嘌呤分阶段灌胃结合环境因素干预并TNBS与乙醇复合物诱导灌肠复合研制的脾肾阳虚型溃疡性结肠炎大鼠模型,符合人类自然发生的UC病变特点和中医证候特点,是较为理想的脾肾阳虚型溃疡性结肠炎模型。     

兰术四草化浊解毒方对溃疡性结肠炎大鼠细胞因子水平的影响

目的探讨兰术四草化浊解毒方对溃疡性结肠炎大鼠细胞因子水平的影响。方法将60只Wistar大鼠随机分为空白组、模型组、阳性药组、兰术四草化浊解毒方大、中、低剂量组,每组10只。除空白组外,其余5组制备溃疡性结肠炎模型。造模后空白组、模型组予蒸馏水灌胃,其余各治疗组给予相应药物灌胃,连续治疗2 w。观察各组大鼠疾病活动指数、结肠黏膜组织病理,血清肿瘤坏死因子(TNF)-α,白细胞介素(IL)-8,IL-10的变化。结果与模型组比较,兰术四草化浊解毒方能够改善结肠黏膜病理变化,减低疾病活动指数评分,降低血清TNF-α及IL-8的含量,升高血清IL-10的含量(P0.05)。与阳性药组比较,兰术四草化浊解毒方大剂量组能够降低血清TNF-α及IL-8的含量,升高血清IL-10的含量(P0.05);兰术四草化浊解毒方中低剂量组能够降低血清TNF-α及IL-8的含量(P0.05),但血清IL-10含量无显著差异(P0.05)。结论兰术四草化浊解毒方治疗溃疡性结肠炎的作用机制可能与降低血清TNF-α及IL-8,升高IL-10的含量有关。     

NF-κB和ICAM-1在溃疡性结肠炎大鼠结肠中表达及中药干预的影响

目的 观察NF-κB和ICAM-1在溃疡性结肠炎大鼠结肠组织的表达及中药复方久泻灵颗粒荆及中药干预的影响.方法 采用异种异体结肠黏膜组织致敏法和乙酸局部灌肠相结合的方法制造动物模型.将Wistar大鼠随机分为空白对照组,模型对照组,阳性对照组,久泻灵颗粒剂大、中、小剂量组.连续给药14 d,末次给药后24 h,处死大鼠后制备结肠组织标本,病理切片HE染色后进行病理组织学评分;免疫组化切片观察结肠组织NF-κB及ICAM-1的表达.结果 久泻灵可显著改善肠黏膜炎症,降低病理组织学评分.久泻灵不同剂量可使NF-κB及ICAM-1表达减弱.结论 久泻灵颗粒剂通过抑制NF-κB激活和ICAM-1表达.阻断炎症的放大效应而达到减轻结肠黏膜炎症,是治疗UC的一种有效中药颗粒剂.     

痛泻要方对溃疡性结肠炎模型大鼠结肠组织中NF-κBp65基因和蛋白表达的影响

目的探讨痛泻要方对溃疡性结肠炎(UC)模型大鼠结肠结肠组织中NF-κB p65蛋白和基因表达的疗效及作用机制。方法将实验动物分为6组,采用2,4,6-三硝基苯磺酸(TNBS)/乙醇灌肠法造模,肉眼观察结肠大体形态损伤并进行评分。以大鼠结肠组织中NF-κB p65为观察指标,采用RT-PCR和免疫组化法检测NF-κB p65蛋白和基因表达水平。结果肉眼观察模型组大鼠结肠组织黏膜层可见炎症和溃疡形成,与空白组比较P<0.05,证实模型成功。模型组大鼠结肠组织NF-κB p65基因和蛋白的表达量均高于空白组,差异有统计学意义(P<0.01);治疗后,痛泻要方高剂量组、中剂量组NF-κB p65基因和蛋白的表达量均较模型组降低(P<0.05、P<0.01)。结论痛泻要方对TNBS/乙醇法UC大鼠模型结肠黏膜NF-κB p65基因和蛋白的表达量有下调作用,提示痛泻要方治疗UC的作用机制之一可能是与NF-κB信号通路被激活有关。     

溃疡性结肠炎大鼠血清白细胞介素-1β、肿瘤坏死因子-α、白细胞介素-4动态表达规律

目的探讨溃疡性结肠炎(UC)大鼠血清白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、IL-4的动态表达规律。方法将60只大鼠随机分为空白组10只、乙醇组10只,模型组40只(3、7、14、21 d各10只),采用TNBS/乙醇灌肠法制备溃疡性结肠炎大鼠模型,于制模后3、7、14、21 d 4个时间点采用ELISA法检测大鼠血清IL-1β、TNF-α、IL-4水平,光镜观察结肠组织形态并评分。结果制模后3 d大鼠结肠出现炎症和溃疡,且随着时间推移而加重,7~14 d溃疡和炎症最为严重,21 d溃疡和炎症已经有所修复。模型组各时间点大鼠血清促炎因子IL-1β、TNF-α均高于空白组和乙醇组,抗炎因子IL-4水平均低于空白组和乙醇组,以7 d和14 d升高或降低更为显著(P0.05、P0.01);7、14 d组与3d组比较,IL-1β、TNF-α水平进一步升高(P0.01),而IL-4水平进一步降低(P0.01);21 d组与7、14 d组比较,IL-1β、TNF-α水平下降,而IL-4水平则升高(P0.05)。结论促炎因子IL-1β、TNF-α和抗炎因子IL-4在UC发病中起重要作用,UC的发病及严重程度与促炎因子IL-1β、TNF-α、IL-4的动态表达及失衡密切相关。     

Expression of IL-23 and IL-17 and effect of IL-23 on IL-17 production in ankylosing spondylitis

The objective of this study was to investigate the expression of IL-23 and IL-17 and the influence of IL-23 on IL-17 production in ankylosing spondylitis (AS) patients. IL-23 and IL-17 levels in the serum and supernatants of cultured peripheral blood mononuclear cells (PBMCs) were determined by ELISA. IL-23p19 mRNA expression in PBMCs were analyzed using RT-PCR. The patients with AS at active stage showed elevated levels of IL-23 and IL-17 in the serum and supernatants of cultured PBMCs. A higher expression of IL-23p19 mRNA in PBMCs of AS patients was also observed. A significantly enhanced production of IL-17 in the supernatants of cultured PBMCs was found in the presence of recombinant IL-23 and this effect was more significant in patients with AS. The results suggest that IL-23 and IL-17 may play critical roles in the pathogenesis of AS and IL-23-stimulated production of IL-17 by PBMCs may be responsible for the development of AS.     

白细胞介素10基因转染对小鼠心脏移植排斥反应中细胞因子表达的影响

目的 :探讨白细胞介素 10 (IL 10 )基因转染对小鼠心脏移植排斥反应中IL 12、IL 15、IL 18和IL 4表达的影响。方法 :采用小鼠颈部心脏移植模型 ,随机分为 3组 :对照组、移植组和IL 10组。于术后第 5天取移植心脏 ,用逆转录聚合酶链式反应 (RT PCR)法观察IL 12、IL 15、IL 18、IL 4及IL 10的表达情况。结果 :移植组IL 12、IL 15、IL 18表达与对照组比较明显升高 ,IL 10、IL 4表达显著降低 (均P <0 .0 1)。IL 10组IL 12、IL 15、IL 18表达与移植组比较明显降低 ,而IL 4及IL 10表达显著升高 (均P <0 .0 1)。结论 :IL 10基因转染抑制心脏移植排斥反应主要与其抑制IL 12、IL 15、IL 18等Th1型细胞因子的表达 ,促进Th2型细胞因子IL 4的表达 ,使免疫反应由Th1型向Th2型偏移有关     

Prognostic values of IL-6, IL-8, and IL-10 in acute pancreatitis

GOALS: The prognostic importance of interleukin-6 (IL-6), IL-8, and IL-10 in the prediction of acute pancreatitis severity. BACKGROUND: Early assessment of severity in acute pancreatitis could help the patients who are at risk of developing complications. Unfortunately, the used prognostic scoring systems generally are only moderately accurate in assessing disease severity. STUDY: We studied 117 consecutive patients with a diagnosis of acute pancreatitis admitted to our hospital during the past 2 years. Laboratory parameters and cytokines were analyzed from serum taken routinely on admission. Severity criteria were noted for each patient using Ranson, Glasgow, and APACHE II scoring systems. Local and systemic complications, developed during a follow-up period, were classified by Atlanta criteria. RESULTS: IL-6 was the only parameter that statistically significantly predicted complicated acute pancreatitis (P<0.05). IL-8 and IL-10 and the 3 prognostic scoring systems used did not properly assess complicated versus noncomplicated acute pancreatitis. CONCLUSIONS: Our prospective study supported the potential importance of IL-6 in the early assessment of complicated acute pancreatitis, but also suggested that pancreatitis classified as complicated in a large number of patients could not be correctly predicted with the Ranson, Glasgow, and APACHE II scoring systems.     

Evaluation of Cardiac Biomarkers and Expression Analysis of IL-1, IL-6, IL-10, IL-17, and IL-25 among COVID-19 Patients from Pakistan

Coronavirus disease 19 (COVID-19) is caused by viral infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Where upregulation of several important biomarkers and multiple organ dysfunction occurs, this study aimed to evaluate the association of cardiac biomarkers and CS induced acute lung damage with disease severity and mortality in survival of COVID-19 patients. A total of 500 COVID-19 patients with elevated cardiac biomarkers were studied for the analysis of myocardial abnormality through cardiac enzymes, inflammatory biomarkers, and the expression analysis of various cytokines, including IL-1, IL-6, IL-10, IL-17, and IL-25 genes. The elevation of various cardiac enzymes including LDH (87%), CK (78.4%), TNI (80.4%), CK-MB (83%), and D-dimer (80.8%) were found correlated (p < 0.001) with COVID-19 infection. Cardiac enzyme elevation was highly associated with an increased level of inflammatory biomarkers such as CRP (14.2%), SAA (11.4%) and erythrocyte sedimentation rate (ESR) (7.8%) (p = 0.001 for all). The quantitative expression analysis of IL-10, 1L-17, and 1L-25 were found to be high, while those of IL-1 and IL-6 were moderately elevated. The death-to-live ratio of COVID-19 patients was 457:43 indicating that the patients having elevated levels of both CKMB, D-dimer, CK and IL-1, IL-6, IL-10 and D-dimer, Troponin, CK and IL-1, IL-10 had high fatality rate (73% and 12% respectively). The current finding concludes that the evaluation of cardiac biomarkers with cytokine storm plays a significant role in COVID-19-associated anatomical organ damage, myocardial injury, and mortality. Physicians should pay special attention to cardiac biomarkers in patients with old age, inflammation, and comorbidities among COVID-19 infections.     

囊尾蚴病患者IL-4、IL-5和IL-10水平检测

目的探讨白细胞介素4(IL-4)、白细胞介素5(IL-5)和白细胞介素10(IL-10)在囊尾蚴病发病中的免疫学作用。方法用双抗体夹心(ELISA)法检测囊尾蚴病患者血清中IL-4、IL-5和IL-10水平。结果囊尾蚴病患者血清中IL-4、IL-5和IL-10水平分别为(152.3±31.2)、(256.4±23.3)和(343.9±20.8)ng/L,正常对照组血清中IL-4、IL-5和IL-10水平分别为(75.0±28.5)、(119.5±17.6)和(106.7±19.6)ng/L,2组比较差异均有统计学意义(t值分别为10.6、27.1和48.4,P<0.001)。结论囊尾蚴感染患者Th2型细胞因子表达水平失常,体液免疫功能升高,说明囊尾蚴感染可致宿主免疫功能紊乱。     

Serum IL-4, IL-10 and IL-6 levels in inflammatory arthritis

As the available in vitro and in vivo data suggest that interleukin (IL)-4 and IL-10 have immunosuppressive activity, our hypothesis was that serum IL-4 and IL-10 levels would correlate inversely with parameters of inflammation in patients with inflammatory arthritis. IL-4 was detected in the serum of 12 out of 140 patients with rheumatoid arthritis (RA), which was increased compared to the proportion found with patients with osteoarthritis (OA; P< 0.02). In addition, IL-4 was detected in the serum of 2 of 19 patients with systemic lupus erythematosus (SLE), 2 of 24 patients with psoriatic arthritis and 1 of 5 patients with Behçet's syndrome. No IL-4 was detected in patients with the following conditions: OA (58 patients), gout (17 patients), ankylosing spondylitis (6 patients), Reiter's syndrome (6 patients), polymyalgia rheumatica (6 patients), temporal arteritis (5 patients) and scleroderma (3 patients). No IL-10 was detected in any of the sera tested. We discuss the possible relevance of these results to the regulation of the immune response evident in inflammatory arthritis.     

IL-12及IL-10在桥本甲状腺炎发病机制中作用的研究进展

桥本甲状腺炎是一种常见的慢性自身免疫性疾病,表现为辅助性T细胞(Th)1占优势。 Th1类细胞因子白细胞介素(IL)-12表达增加,在该病的诱发及慢性迁延中起重要作用,Th2类细胞因子IL-10表达的下调也与该病有关,且随病情变化二者表达水平有所不同。因此,这些细胞因子可作为病情变化的监测指标,并且可通过调节细胞因子的表达水平从而使失衡的Th1／Th2细胞趋于平衡。这可能为桥本甲状腺炎的治疗开拓一条新途径。     

A complex of the IL-1 homologue IL-1F7b and IL-18-binding protein reduces IL-18 activity

IL-1F7 was discovered in expressed sequence tag databases as a member of the increasing family of proteins sharing sequence homology to IL-1alpha/beta, IL-1Ra, and IL-18. In the present study using immunohistochemical staining, IL-1F7 was localized in human peripheral monocytic cells, suggesting its role in immune regulation. Recombinant human IL-1F7b was shown to bind to the IL-18Ralpha but without IL-18 agonistic or antagonistic function. Using chemical cross-linking, we observed that, unlike IL-18, IL-1F7b fails to recruit the IL-18Rbeta chain to form a functionally active, ternary complex with the IL-18Ralpha chain. IL-1F7b shares two conserved amino acids with IL-18 (Glu-35 and Lys-124), which participate in the interaction of IL-18 with the IL-18Ralpha chain as well as the IL-18-binding protein (IL-18BP), a secreted protein that neutralizes IL-18 activity. In testing whether IL-1F7b interacts with IL-18BP, we unexpectedly observed that IL-1F7b enhanced the ability of IL-18BP to inhibit IL-18-induced IFNgamma by 25-30% in a human natural killer cell line. This effect was observed primarily at limiting concentrations of IL-18BP (3.12-12.5 ng/ml) and at a 50- to 100-fold molar excess of IL-1F7b. Similar results were obtained by using isolated human peripheral blood mononuclear cells. To study the molecular basis of this effect we performed binding studies of IL-1F7b and IL-18BP. After cross-linking, a high molecular weight complex consisting of IL-1F7b and IL-18BP was observed on SDS/PAGE. We propose that after binding to IL-18BP, IL-1F7b forms a complex with IL-18Rbeta, depriving the beta-chain of forming a functional receptor complex with IL-18Ralpha and thus inhibiting IL-18 activity.