三仁汤对温病湿热证大鼠模型白介素及免疫球蛋白的影响

[目的]探讨三仁汤对温病湿热证大鼠模型免疫因子的影响.[方法]将SD大鼠分为6组：空白对照组,模型组,三仁汤高、中、低剂量组,阳性对照组（血脂康组）.除空白对照组外,其余各组每日给予高脂饲料及人工气候箱高温环境喂养,并给予大肠埃希杆菌2次灌胃引起感染制作高脂温病湿热证大鼠模型,给予三仁汤药液进行干预.[结果]与模型组比较,白介素：IL-1β、IL-8、IL-10、IL-6、肿瘤坏死因子等均显著降低;免疫球蛋白：IgA、IgM、IgG,差异无统计学意义.[结论]通过本实验证实三仁汤水煎剂能使温病湿热证大鼠模型血清中白介素及肿瘤坏死因子降至正常,从而调节免疫功能,有效改善湿热证症状,缩短温病湿热证的治疗时间.     

久泻灵颗粒对脾肾阳虚型溃疡性结肠炎大鼠IL-2、IL-4、IL-10表达的影响

目的探讨不同剂量久泻灵颗粒治疗前后脾肾阳虚型溃疡性结肠炎大鼠血清及结肠中白细胞介素(IL)-2、IL-4、IL-10及其基因表达的变化。方法大黄水煎液灌胃+肌注氢化可的松+三硝基苯磺酸(TNBS)/乙醇灌肠法复建动物模型。90只Wistar大鼠随机分为空白组、模型组、久泻灵颗粒高、中、低剂量组及柳氮磺吡啶(SASP)组,药物干预后,镜下观察病理组织学变化进行评分,采用酶联免疫法检测各组大鼠血清中IL-2、IL-4、IL-10含量,RT-q PCR法检测基因表达。结果相比空白组,模型组大鼠血清中IL-2、IL-4、IL-10含量及结肠组织中的基因表达均降低(P<0.05);相比模型组,各治疗组大鼠血清中IL-2、IL-4、IL-10含量及结肠组织中的基因表达均升高(P<0.05),作用最显著的是久泻灵颗粒高剂量组(P<0.05)。结论久泻灵颗粒调节免疫活性,促进脾肾阳虚型溃疡性结肠炎模型大鼠血清中IL-2、IL-4及IL-10的分泌,从而抑制炎症发生,保护结肠黏膜。     

温病湿热证大鼠IL-23表达水平的变化及应用加味藿朴夏苓汤干预后的影响

目的观察大鼠血清与舌组织IL-23表达水平的变化以及应用加味藿朴夏苓汤干预后的影响,探讨IL-23在湿热证发病中的作用和意义。方法 96只大鼠随机分为正常组、模型组和干预组。多因素复合造模方法制备温病湿热证大鼠模型,干预组第25天起予加味藿朴夏苓汤治疗,连服7 d。于造模后4、24、48、72 h四个时相点分批处死大鼠并取材。ELISA法检测大鼠血清IL-23的水平,SP免疫组化法检测舌组织IL-23的表达。结果湿热模型组大鼠血清与舌IL-23表达水平在各时相点均显著高于正常组(P0.01),药物干预组则在各时相点均显著低于模型组(P0.01)。随时间点变化模型鼠血清与舌IL-23均呈逐渐下降趋势,在4 h时最高;血清IL-23的含量水平48 h和72 h时相点分别与4 h时相点比较差异有统计学意义(P0.05),72 h时相点与24 h时相点比较差异亦有统计学意义(P0.05);舌IL-23的表达水平在各时相点分别比较差异均有统计学意义(P0.01)。在湿热模型组病情分级为轻、中、重度的大鼠血清与舌IL-23的表达水平均呈逐渐升高趋势,组间比较差异均有统计学意义(P0.01);均与病情的严重程度呈正相关(P0.01)。结论 IL-23参与了湿热证的发生、发展过程,其表达水平变化与湿热证的病情严重程度密切相关。加味藿朴夏苓汤可减少温病湿热证大鼠IL-23的表达,抑制炎症反应而减轻病情严重程度。     

白细胞介素-12及白细胞介素-18致小鼠脾虚的研究

目的：观察白细胞介素-12(IL-12)及白细胞介素-18(IL-18)能否导致脾虚，研究脾虚与IL-12及IL-18的关系。方法：60只小鼠随机分为脾虚组、IL组和对照组。采用利血平制作脾虚动物模型组，IL组每日腹腔注射IL-12、IL-18。采用免疫分析技术检测3组小鼠血浆IL-12、IL-18的含量。结果：IL-12及IL-18引起明显脾虚证的表现，与利血平制作脾虚动物模型组相似。脾虚组和IL组血浆IL-12、IL-18的含量明显升高。结论：IL-12、IL-18可导致脾虚，血浆IL-12、IL-18的含量可作为脾虚证的实验室参考指标。     

空肠灌注生大黄对重症急性胰腺炎大鼠的作用

目的探讨生大黄对重症急性胰腺炎(SAP)大鼠血清白细胞介素-6(IL-6)、白细胞介素-8(IL-8)和胰腺组织病理学改变的影响。方法 36只大鼠随机分为正常对照组(假手术组,n=12)、模型组(SAP,n=12)和治疗组(生大黄组,n=12),以5%的牛磺胆酸钠逆行胆胰管注射制备大鼠SAP模型,采用放射免疫法检测大鼠血清IL-6、IL-8浓度。观察胰腺组织湿干重比。光镜下评估胰腺组织病理学积分。结果模型组和治疗组大鼠血清IL-6、IL-8水平明显高于正常对照组,其中治疗组明显低于模型组,P0.01。治疗组胰腺湿干重比及病理组织学评分均显著低于模型组,P0.01。结论生大黄可以使SAP大鼠血清IL-6、IL-8显著降低,并减轻胰腺的病理组织学改变。     

复元胶囊治疗气虚血瘀证类风湿关节炎的机制

目的 研究复元胶囊及其与甲氨蝶呤(MTX)联用对气虚血瘀证类风湿关节炎(RA)的治疗机制.方法 用Ⅱ型胶原诱导大鼠RA模型后,采用疲劳、饥饿、高脂饮食及寒湿等方法建立气虚血瘀证模型大鼠,设空白对照组、模型组、复元胶囊组、MTX组、复元胶囊联用MTX组(联用组).各组以相应的药物灌胃,于8w后,用酶联免疫吸附试验法(ELISA)检测血清肿瘤坏死因子α(TNF-α),放射免疫法检测血清白细胞介素-1β(IL-1β),白细胞介素-6(IL-6)水平.结果 与模型组相比,复元胶囊组、MTX组及联用组大鼠关节肿胀明显减轻,血清TNF-α、IL-1B、IL-6均有所下降(P＜0.05),其中以联用组较优(P＜0.05).结论 复元胶囊联用MTX可明显改善气虚血瘀证RA大鼠的症状,其作用机制可能与抑制大鼠TNF-α、IL-1B、IL-6等炎症介质的表达有关,由此为复元胶囊治疗气血血瘀证RA大鼠提供了科学依据.     

清热利湿法对湿热证动物模型的影响

目的：探讨清热利湿法的作用机制。方法：采用综合因素造模（饮食加气候环境加致病生物因子）复制成温病湿热证动物模型,给予清热祛湿方药清香散,观察动物模型给药后的变化。结果：该模型无论从发病条件、病变脏腑,还是主要症状、体征均近似于中医湿热证型,造模后体温上升,小肠吸收功能明显下降,红细胞ＳＯＤ活性下降,ＭＤＡ 升高,肛门红肿,大便溏泄。经清香散治疗后,上述症状、体征及其他指标均得到明显改善。结论：清热利湿法治疗湿热证的机制可能与改善症状、体征,保护小肠吸收功能,抗机体氧化反应等作用有关。     

大鼠实验性卡氏肺孢子虫肺炎中IL-2,IL-6的变化

目的 建立大鼠实验性卡氏肺孢子虫肺炎的模型,观察血清和肺泡灌洗液中IL-2和IL-6的变化.方法 给SD大鼠皮下注射地塞米松磷酸钠建立卡氏肺孢子虫肺炎动物模型,酶免法检测支气管肺泡灌洗液中IL-2和IL-6含量及血清中IL-6含量;放免法检测血清中IL-2含量.结果 感染组大鼠血清和肺泡灌洗液中IL-2和IL-6含量均显著高于正常对照组.结论 卡氏肺孢子虫肺炎大鼠血清和肺泡灌洗液中IL-2和IL-6升高.     

慢性乙型肝炎中医证型与IL-2、IL-10、IL-12、IFN-γ水平的关系初探

探讨慢性乙型肝炎(以下简称慢乙肝)中医证型与血清白细胞介素-2(IL-2)、白细胞介素-10(IL-10)、白细胞介素-12(IL-12)、干扰素-γ(IFN-γ)含量的关系。方法:将50例慢乙肝患者按照中医辨证分型标准分为湿热中阻、肝郁脾虚、肝肾阴虚、瘀血阻络、脾肾阳虚5型,采用双抗体夹心ELISA方法检测血清IL-2、IL-10、IL-12、IFN-γ水平,同时与20例体检健康者的检测水平相比较。结果:除脾肾阳虚型的IL-10和瘀血阻络型的IL-12低于正常对照组外,其余的证型其检测结果均高于正常对照组,P<0.05;中医辨证分型各组总体差异明显,P<0.05;中医证型各组间比较,湿热中阻、肝郁脾虚、瘀血阻络及脾肾阳虚的IL-2差异明显,P<0.05,IL-10在各组间无明显差异,肝郁脾虚的IL-12与湿热中阻和肝肾阴虚差异明显,P<0.05,肝郁脾虚的IFN-γ与肝肾阴虚、瘀血阻络、脾肾阳虚差异明显,P<0.05。结论:慢乙肝细胞因子水平与其中医辨证分型有一定的相关性,可作为慢乙肝中医辨证分型的客观依据之一。     

慢性乙型肝炎中医证型与IL-2、IL-1 O、IL-1 2、IFN-γ水平的关系初探

目的:探讨慢性乙型肝炎(以下简称慢乙肝)中医证型与血清白细胞介素-2(IL-2)、白细胞介素-10(IL-10)、白细胞介素-12(IL-12)、干扰素-γ(IFN-γ)含量的关系.方法:将50例慢乙肝惠者按照中医辨证分型标准分为湿热中阻、肝郁脾虚、肝肾阴虚、瘀血阻络、脾肾阳虚5型,采用双抗体夹心ELISA方法检测血清IL-2、IL-10、IL-12、IFN-γ水平,同时与20例体检健康者的检测水平相比较.结果:除脾肾阳虚型的IL-10和瘀血阻络型的IL-12低于正常对照组外,其余的证型其检测结果均高于正常对照组,P＜0.05;中医辨证分型各组总体差异明显.P＜0.05;中医证型各组间比较,湿热中阻、肝郁脾虚、瘀血阻络及脾肾阳虚的IL-2差异明显,P＜0.05,IL-10在各组间无明显差异,肝郁脾虚的IL-12与湿热中阻和肝肾阴虚差异明显,P＜0.05,肝郁脾虚的IFN-γ与肝肾阴虚、瘀血阻络、脾肾阳虚差异明显,P＜0.05.结论:慢乙肝细胞因子水平与其中医辨证分型有一定的相关性,可作为慢乙肝中医辨证分型的客观依据之一.     

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.     

三仁汤对脾胃湿热证大鼠神经内分泌免疫功能影响的研究

目的探讨三仁汤对脾胃湿热证大鼠神经内分泌免疫功能相关指标的影响作用。方法将50只雄性Wistar大鼠随机分为正常组、模型组、三仁汤(高、中、低剂量)组,利用复合因素复制脾胃湿热证动物模型。通过称量法计算胸腺和脾脏指数,同时采用放射免疫法检测大鼠血浆促肾上腺皮质激素释放激素(CRH)、促肾上腺皮质激素(ACTH)、血清皮质醇(Cor)、白介素2(IL-2)的水平。结果造模成功后的各组大鼠血浆CRH、ACTH及血清Cor升高,三仁汤治疗组各剂量对其均有降低作用。造模后各模型组大鼠胸腺、脾脏指数及血清IL-2降低,三仁汤(高、中、低剂量)组可以升高模型组大鼠上述指标的水平(P0.05);且以上两种结果均以中剂量组效果最好。结论复合因素造模可以使脾胃湿热证大鼠神经内分泌免疫功能发生异常改变,三仁汤可以调节脾胃湿热证大鼠上述功能,这可能是清热祛湿的机理之一。     

慢性病毒性肝炎279例病理诊断与中医证型的关系

目的:探讨慢性病毒性肝炎病理组织学诊断与中医辨证分型之间的关系,为中医辨证提供客观依据。方法:279例均为住院患者,男227例,女52例。全部病例经肝活检证实,其中轻度142例,中度91例,重度46例。慢性乙型肝炎274例,慢性丙型肝炎5例。中医辨证:湿热中阻53例,肝郁脾虚64例,肝肾阴虚29例,脾肾阳虚7例,血瘀血热101例,气阴两虚25例。临床治疗以辨证施治为主。结果:(1)279例慢性肝炎在病理诊断分型中,轻度占50.9%、中度占32.6％、重度占16.4％。(2)在轻度慢性肝炎中,湿热中阻、肝郁脾虚及肝肾阴虚证明显高于血瘀血热证.P=0.01、P<0.05。(3)湿热中阻、肝郁脾虚证的病理诊断分布情况依次为轻度>中度>重度,P<0.01、P<0.05;血瘀血热证轻度与中度分别>重度,P<0.05。但该证在重度中的发生率高于其他证型。(4)脾肾阳虚与气阴两虚证在各病理分型中的分布均无显著差异,P>0.05。结论:(1)慢性肝炎患者以轻度居多,占半数以上。(2)慢性肝病的病变早期以湿热中阻、肝郁脾虚为主证特点,病变部位多在气分;随着肝脏病理损害加重,病变部位及主导证型渐由气分至血分,以血瘀血热为主证特点。(3)治疗上主张早期宜注重清解湿热,疏肝健脾;中、晚期宜重视活血化瘀,凉血解毒。     

Blockade of the interleukin-21/interleukin-21 receptor pathway ameliorates disease in animal models of rheumatoid arthritis

OBJECTIVE: Interleukin-21 (IL-21) is a T cell-derived cytokine that modulates T cell, B cell, and natural killer cell responses. In this study, the effects of blocking IL-21 were examined in 2 rodent models of rheumatoid arthritis (RA) to determine whether IL-21 contributes to their pathologic processes. METHODS: DBA/1 mice were immunized with bovine type II collagen and then treated with murine IL-21 receptor Fc fusion protein (IL-21R.Fc), which was initiated after the onset of arthritis symptoms in 10% of the cohort. The mice were assessed 3 times per week for signs of disease, including histologic features as well as serum cytokine, Ig, and cytokine messenger RNA (mRNA) levels in the paws. In a separate experiment, Lewis rats were immunized with Freund's complete adjuvant followed by administration of IL-21R.Fc at the peak of inflammation in the joints. Rats were assessed daily for histologic features and for scoring of arthritis severity. In addition, the effects of IL-21R.Fc on the production of interferon-gamma (IFNgamma) by T cells were examined. RESULTS: Treatment of DBA/1 mice with IL-21R.Fc reduced the clinical and histologic signs of collagen-induced arthritis. Nonspecific IgG1 levels were decreased in response to treatment. The levels of IL-6 mRNA in the paws and the serum IL-6 levels were decreased after treatment with IL-21R.Fc. IFNgamma mRNA levels were increased in the paws, and the addition of IL-21R.Fc to collagen-activated lymph node cultures enhanced the levels of IFNgamma. Collagen-specific spleen cell responses in IL-21R.Fc-treated mice were observed as reduced levels of IFNgamma and increased levels of IL-6. Treatment of Lewis rats with IL-21R.Fc after induction of adjuvant-induced arthritis resulted in reversal of disease signs and improvements in histologic parameters. CONCLUSION: These findings demonstrate a pathogenic role for IL-21 in animal models of RA, and support consideration of IL-21 as a therapeutic target in human RA.     

Serum levels of IL-10, IL-6, IL-1ra, and sIL-2R in patients with psoriatic arthritis

Our objective was to evaluate the levels of interleukin-6 (IL-6), soluble receptors of IL-2 (sIL-2R), IL-10, and IL-1 receptor antagonists (IL-1ra) in the serum of patients with psoriatic arthritis (PsA) and to assess the correlation between these levels and parameters of clinical activity of skin and joint disease. In total, 34 patients with PsA and ten healthy volunteers participated in the study. Assessment of joint disease included duration of morning stiffness, number of tender and swollen joints, right and left grip, the presence of inflammatory spinal back pain, and Schober test. Current severity of skin disease was graded according to the psoriasis area and severity index (PASI). Erythrocyte sedimentation rate (ESR) was determined as a marker of disease activity. Serum levels of IL-6, sIL-2R, IL-1ra, and IL-10 were measured by an enzyme immunoassay kit. Significantly higher serum levels of IL-6, sIL-2R, IL-1ra, and IL-10 were found in patients with PsA in comparison with healthy volunteers. A statistically significant correlation was found between levels of sIL-2R and PASI, whereas no association was found with clinical parameters of joint severity. Levels of IL-1ra correlated with the number of tender and swollen joints. No correlation was found between levels of IL-6, IL-10, and clinical parameters of skin and joint severity. In the group of patients with PsA, serum levels of sIL-2R clearly correlated with severity of skin disease, whereas levels of IL-1ra were associated with joint severity. Received: 18 June 1999 / Accepted: 1 October 1999     

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.     

中药复方清肠汤对大鼠实验性结肠炎的疗效观察

[目的]观察中药复方清肠汤对实验性结肠炎大鼠的治疗效果.[方法]将40只SD大鼠随机分为空白对照组（A组）、模型组（B组）、西药对照组（C组）、中药常规剂量组（D组）、中药大剂量组（E组）和湿热组（F组）,采用乙酸灌肠加葡聚糖硫酸钠自由饮用的方法制作大鼠实验性结肠炎模型,F组再给予高糖高脂饮食喂养并放置高温高湿环境处理以模拟大肠湿热证形成条件,造模同时D、E、F组给予清肠汤灌胃,C组给予柳氮磺嘧啶（SASP）混悬液灌胃,每日2次,治疗7d后再次以乙酸灌肠,各组均连续灌胃14d,治疗前后每日观察记录大鼠体质量、饮食及活动情况,重点观察粪便的性状改变,造模前后检测肛温,对死亡大鼠进行解剖并观察肠道病理改变.治疗结束后对各组大鼠疾病活动指数（DAD、肠黏膜损伤评分及组织病理学评分（HI）进行统计学评价和分析.[结果]与A组相比,造模后各组大鼠DAI评分、肠黏膜损伤评分和HI评分明显上升（P＜0.05）;给药后,D组和F组的DAI评分有明显下降（P＜0.05）,各组肠黏膜损伤评分和HI评分明显降低（P＜0.05）,F组肠道HI评分明显低于D组（P＜0.05）.[结论]清肠汤能改善实验性结肠炎模型大鼠的症状,并且与SASP一样均能使模型大鼠的肠黏膜损伤减轻.而清肠汤对湿热证模型组大鼠肠道病理损伤的改善优于非湿热证模型组,体现了中医辨证论治的优势.