牛磺胆酸对佐剂性关节炎大鼠血清中IgG、IL-1β、IL-6和TNF-α的影响

目的研究牛磺胆酸对佐剂性关节炎大鼠血清中IgG、细胞因子IL-1β、IL-6和TNF-α水平的影响,进一步探讨该药物的作用机制。方法用Freund′s完全佐剂复制佐剂性关节炎大鼠模型,观察牛磺胆酸对大鼠足肿胀的作用;检测药物对大鼠血清中IL-1β、IL-6和TNF-α含量的影响。结果与模型组比较,牛磺胆酸促进佐剂性关节炎大鼠足肿胀,显著提高IgG、IL-1β、IL-6的含量,而对TNF-α含量则无影响。同时对免疫器官胸腺和脾脏的重量无影响。结论牛磺胆酸可增强佐剂性关节炎大鼠的免疫功能,对细胞因子的生成有调节作用。     

以MMP标记法检测新风胶囊对AA大鼠滑膜及胸腺细胞凋亡的影响

〔目的〕观察以线粒体膜电位 (MitochondrialMembranePotential,MMP)标记法检测新风胶囊对佐剂性关节炎 (ad juvantarthritis,AA)大鼠滑膜及胸腺细胞凋亡的影响 ,探讨新风胶囊的作用机制。〔方法〕采用弗氏完全佐剂造成佐剂性关节炎 (AA)大鼠模型 ,设立正常对照组、模型对照组、甲氨喋呤 (MTX)对照组、雷公藤多甙 (TriperygiumWilfordiiPolycorideTablet ,TPT)对照组和新风胶囊 (XinfengCapsule,XFC)治疗组。记录各组大鼠的关节炎指数 ,应用流式细胞仪 (FCM)以线粒体膜电位 (MMP)标记法测定各组大鼠滑膜及胸腺细胞凋亡率。〔结果〕与治疗前相比 ,新风胶囊组、雷公藤组及MTX组治疗后大鼠的关节炎指数显著降低 (P <0 .0 5～ 0 .0 1) ;模型组滑膜及胸腺细胞凋亡率显著低于正常对照组 (P <0 .0 5 ) ,新风胶囊组细胞凋亡率显著高于模型组、雷公藤组及MTX组 (P <0 .0 5～ 0 .0 1)。〔结论〕新风胶囊与MTX、雷公藤一样能降低AA大鼠关节炎指数 ,在促进线粒体电位介导的滑膜及胸腺细胞凋亡方面优于MTX和雷公藤。促进滑膜细胞凋亡 ,抑制滑膜增生以及促进胸腺细胞凋亡 ,抑制自身免疫反应可能是新风胶囊降低关节炎指数、清除关节炎肿胀的机理之一。     

荔枝壳花青素对大鼠佐剂性关节炎的治疗作用研究

目的观察荔枝壳花青素(litchi pericarp anthocyanins,LPA)对Freund’s完全佐剂诱导的大鼠佐剂性关节炎的治疗作用。方法将60只Wistar雄性大鼠随机分为:正常对照、模型对照、LPA高、中、低(300,150,75mg/kgbw)剂量及醋酸泼尼松治疗(醋酸泼尼松30mg/kg)6组,除正常对照组外,其余各组均用Freund’s完全佐剂诱导大鼠佐剂性关节炎模型。正常对照组和模型组灌胃等量生理盐水,实验组分别灌胃LPA和醋酸泼尼松。定期检测动物左后足厚度,4w后测定血清MDA、SOD和GSH-Px等抗氧化指标及血清NO、白介素IL-1β等炎症因子的含量。结果 LPA高剂量可显著降低大鼠左侧继发性足肿胀厚度,降低血清中NO、细胞白介素IL-1β和MDA的含量,提高机体血清的GSH-Px、SOD活力水平。其对佐剂性关节炎(Adjuvant-induced Arthritis,AA)大鼠的治疗效果优于醋酸泼尼松或与之相当。结论 LPA可一定程度缓解大鼠佐剂性关节炎引起的机体不适症状,其作用机制可能与LPA提高机体抗氧化能力和抗炎水平有关。     

改良弗氏完全佐剂制备大鼠类风湿性关节炎模型

[目的]建立改良弗氏完全佐剂制备大鼠类风湿性关节炎模型.[方法]将液体石蜡、Tweem80按3:1的比例混合均匀,高压灭菌后4℃保存,使用时加入卡介苗(10mg/ml)、Ⅱ型胶原纤维(5mg/ml)配制成弗氏完全佐剂(CFA),充分研磨混匀乳化后,取0.1ml注射于大鼠左后足垫皮内致敏.[结果]AIA大鼠致炎后15h,致炎侧足肿胀达高峰,表现为早期的炎症反应,持续2～3d逐渐减轻,7～8d后再度肿胀,继发病变于致炎后10d左右出现,表现为对侧和前足肿胀,且进行性加重,大鼠行动不便,体重下降,表现类似人类RA,造模成功.[结论]改良弗氏完全佐剂可成功制备大鼠类风湿性关节炎模型.     

苗药飞龙掌血醇提物对佐剂性关节炎模型大鼠Foxp3+CD4+CD25+调节T细胞和血清因子影响的研究

目的:探讨苗药飞龙掌血醇提物对佐剂性关节炎模型大鼠Foxp3+CD4+CD25+调节T细胞和血清IL-6、TNF-α、PGE2的影响。方法:将140只SD大鼠随机分为正常组、模型组、西药组、中药组和飞龙掌血醇提物低、中、高剂量组,每组20只。除正常组外,其余6组大鼠均制作佐剂性关节炎模型,第14天后,各组给予相应的药物灌胃,2次/d,连续给药14d。检测各组大鼠足趾肿胀度、关节炎指数,血清IL-6、TNF-α、PGE2含量和Foxp3+CD4+CD25+调节T细胞百分数。结果:与正常组比较,模型组大鼠给药前后原发性、继发性足趾肿胀度及关节炎指数升高,差异有统计学意义(P0.05)。与给药前比较,西药组、中药组、飞龙掌血醇提物低、中、高剂量组大鼠给药后原发性、继发性足趾肿胀度及关节炎指数降低,差异有统计学意义(P0.05)。与模型组比较,西药组、中药组、飞龙掌血醇提物低、中、高剂量组大鼠给药后原发性、继发性足趾肿胀度及关节炎指数降低,血清IL-6、TNF-α、PGE2含量降低,Foxp3+CD4+CD25+调节T细胞百分数升高,差异有统计学意义(P0.05)。结论:飞龙掌血醇提物对佐剂性关节炎大鼠具有抗炎的作用,其机制可能与升高调节T细胞水平有关。     

丹皮酚联合甲氨蝶呤对大鼠佐剂性关节炎的治疗作用

目的：研究丹皮酚联合甲爨蝶呤对佐剂性关节炎（从）大鼠的治疗作用。方法：弗氏完全佐剂免疫诱导大鼠AA,随机分为正常组,模型组,丹皮酚（200mg／kg,ig）组,甲氨蝶呤（0．75mg／kg,ig）组和丹皮酚联合甲氨蝶呤（200mg±0．75mg／kg,ig）组。给药后对AA大鼠做整体观察,足爪肿胀度和关节炎指数评分测定,血清中TNF-α IL-1β水平测定。结果：与正常组比较,模型组大鼠足爪肿胀度和关节炎指数评分明显升高,血清中TNF-α和 IL-1β水平显著升高;联合给药组相较于单独给药组,明显抑制大鼠足爪肿胀度和关节炎指数评分,降低血清中TNF-α 和 IL-1β 水平。结论：丹皮酚联合甲氨蝶呤显著改善AA大鼠多发性关节炎病变症状,降低血清中TNF-α和IL-1β 水平,提示丹皮酚联合甲氨蝶吟可能时娄风湿关节炎具有治疗作用．     

桑椹花青素对大鼠佐剂性关节炎抑制作用

目的 研究桑椹花青素对佐剂性关节炎的抗炎功效.方法 将60只大鼠随机分为6组,在除正常对照组外的所有大鼠右后足跖皮内注射弗氏完全佐剂0.1 ml,观察大鼠左后足肿胀度,用比色法检测动物血清的谷胱甘肽过氧化物酶(GSH-Px)活性、超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量、总抗氧化能力(T-AOC)及一氧化氮(NO)的水平;用放射免疫法测定血清和继发性炎症区域炎症因子白细胞介素-1(IL-1)和肿瘤坏死因子(TNF)的水平.结果 桑椹花青素对大鼠继发性足肿胀有一定抑制作用,与模型组相比,桑椹花青素高、中、低组左侧继发性足肿胀度明显低于模型组,差异有统计学意义(P<0.05);能够明显提高大鼠血清中的GSH-Px、SOD活力及T-AOC水平,降低血清中MDA含量;降低血清及关节浸液中IL-1β和TNfa的水平,在抑制血清NO的合成中有一定的作用.结论 桑椹花青素对佐剂性关节炎具有一定抑制作用,其抗炎活性可能与其较强的抗氧化活性有关.     

有效抗生育低剂量雷公藤糖浆对佐剂性关节炎大鼠免疫功能的影响

为全面观察具有抗生育作用的低剂量雷公藤糖浆对机体免疫功能的影响,在研究其对正常小鼠免疫功能影响这一早期工作基础上,观察其对佐剂性关节炎(adjuvant arthritis, AA)大鼠免疫功能的影响,实验结果表明,AA大鼠脾T淋巴细胞ConA诱导增殖反应和产生白细胞介素2(Interleukin2, IL-2)能力与正常对照组相比明显降低(P<0.01);AA大鼠腹腔巨噬细胞(macrophage, Mφ)产生白细胞介素1(interleukin 1, IL-)能力与正常对照组相比明显提高(P<0.01)。有效抗生育低剂量雷公藤糖浆对AA大鼠脾T淋巴细胞ConA诱导增殖反应和产生IL-2能力以及腹腔Mφ产生IL-1能力均无明显影响。上述结果提示有效抗生育作用的低剂量雷公藤糖浆对AA大鼠免疫功能无明显影响。     

白芍总苷对大鼠佐剂关节炎抗炎作用及机制研究

目的 探讨白芍总苷(total glucosides of paeonia:TGP)对佐剂关节炎大鼠足爪组织中核转录因子NF-κB/p65蛋白表达的抑制作用和对大鼠足爪组织病理改变的影响及血清中血管内皮生长因子(VEGF)和白介素-17(IL-17)含量的影响.方法 建立Ⅱ型胶原诱导的佐剂关节炎大鼠模型,用免疫组化染色法检测足爪组织中NF-κB/p65蛋白的表达.病理切片观察不同剂量的TGP对佐剂关节炎大鼠的治疗效果.用ELISA法检测佐剂关节炎大鼠血清中VEGF和IL-17的含量.结果 大、中剂量组的胞浆内NF-κB/p65的阳性表达比模型对照组明显降低(P＜0.01),TGP大、中剂量治疗组与地塞米松组能明显改变佐剂关节炎大鼠皮下组织细胞排列、炎性细胞浸润及血管增生现象,TGP小剂量组对改善佐剂关节炎大鼠足部皮肤的病理状况无明显作用.中、大剂量的TGP组和地塞米松组血清VEGF和IL-17的含量明显降低(P＜0.01).结论 TGP能抑制佐剂关节炎大鼠的炎症反应,其机制可能是TGP可下调NF-κB/p65蛋白的表达,降低炎性细胞因子IL-17和血清VEGF的产生,最终抑制血管增生及炎性细胞浸润.     

有效抗生育低剂量雷公藤糖浆对佐剂性关节炎大鼠免疫功…

为全面观察具有抗生育作用的低剂量雷公藤糖浆对机体免疫功能的影响，在研究其对正常小鼠免疫功能影响这一早期工作基础上，观察其对佐剂性关节炎（ＡＡ）大鼠免疫功能的影响，实验结果表明，ＡＡ大鼠脾Ｔ淋巴细胞ＣｏｎＡ诱导增殖反应和产生白细胞介素２（ＩＬ－２）能力与正常对照组相比明显降低（Ｐ〈０．０１）；ＡＡ大鼠腹腔巨噬细胞（Ｍφ）产生白细胞介素１（ＩＬ－１）能力与正常对照组相比明显提高（Ｐ〈０．０１）。有效抗     

Tripterygium wilfordii, a Chinese herb effective in male fertility regulation

A refined extract from the root xylem of Tripterygium wilfordii Hook. f. (the so-called multi-glycosides of the plant), available in the market as tablets for the long-term treatment of rheumatoid arthritis and various skin disorders, has recently been shown to possess a powerful antifertility effect in male rats and in men after oral administration at dose levels not showing apparent toxicity or side effects. Fertility appears to be reversible after cessation of treatment. Moreover, preliminary data indicated that the effective antifertility dose in men is only 1/3 of the recommended dose for the treatment of rheumatoid arthritis or skin diseases. This fact supports additional optimism that the side effects of this small dose will be much less as compared with those of the regular dose level. However, a large amount of further investigation is required before one can predict the future of the drug, which seems to hinge upon the successful isolation of the active principle(s) and the careful toxicological evaluation of the safety of the latter. The present paper is a review article summarizing the chemistry, the general pharmacology and the fertility regulatory effect of the plant.     

类风湿关节炎二线药物不良反应回顾性调查

目的：比较不同二线药物治疗类风湿关节炎（RA）不良反应的发生率和撤药率。为临床医生选择二线药物提供决策依据。方法：采用回顾性调查方法由经过训练的调查员调查864例RA病人以往服用过的二线药物，对这些药物有无不良反应和有何种不良反应。结果：上腹不适为二线药物最常出现的不良反应。甲氨喋呤的胃肠道不良反应（32．3％）最多见；青霉胺和风痛宁突出表现为皮肤瘙痒性皮疹（分别为20．6％和13．7％）。青霉胺肾脏损害症状出现危险性明显高于其他药物（是对比危险率的14．5倍）。雷公藤最常见的不良反应是月经周期的紊乱（14．4％），柳氮磺吡眩要是上腹不适（39％），纳差（7．3％）、恶心（7．3％），眼部不适，视力下降（19．6％）是使用氯喹最常见的不适主诉，二线药物不良反应程度是有差别的，不良反应是引起各种二线药物撤药的主要原因，甲氨喋呤撒药率最低，甲氨喋呤和青霉胺联用不增加不良反应的发生率和严重程度。结论：熟悉二线药物不良反应，有利于临床医师选择药物和治疗方案，注意监测和对症处理不良反应，二线物药仍然是安全的。     

不同工艺黑木耳不溶性膳食纤维的理化特性研究

目的探讨不同处理工艺对黑木耳不溶性膳食纤维(IDFs)营养成分及理化性质的影响。方法采用水、纤维素酶以及碱液分别制备不同种类膳食纤维,通过营养成分、水合能力(包括吸水力、持水性、膨胀率、膨胀力)、吸附性能(包括持油性、胆固醇及胆汁酸吸附能力、亚硝酸根离子吸附能力)测定,分析处理工艺对黑木耳IDFs的影响。结果黑木耳子实体与不同IDFs间营养成分存在一定差异,尤其总膳食纤维(TDF)与氨基糖差异较大,其中碱处理获得的IDF的TDF与氨基糖含量最高,分别是子实体的2.79倍与1.17倍,水处理与酶处理IDFs比子实体略高;处理工艺对黑木耳IDFs的理化性质亦产生较大影响,酶处理获得的IDF的水合能力与吸附性(除持油力略低于子实体外)最好,其次为水处理,均优于子实体,其中影响最大的是吸附胆酸钠能力,1 mmol胆酸钠浓度下,酶处理IDF吸附胆酸钠能力可达子实体的4.04倍,而碱处理IDF水合能力与吸附性均差于子实体。结论不同处理工艺对黑木耳IDFs的营养成分及理化性质均产生较大影响,本实验为黑木耳膳食纤维的开发利用提供了基础研究数据。     

复方雷公藤制剂对活动期类风湿性关节炎相关实验室指标的影响

目的观察复方雷公藤制剂对活动期类风湿性关节炎(RA)患者红细胞沉降率(ESR)、C-反应蛋白(CRP)、抗链球菌"O"(ASO)、类风湿因子(RF)和抗环瓜氨酸肽抗体(抗CCP)的影响。方法将141例RA患者按病程分为A、B、C 3组,每组再按病情分为湿热型和寒湿型。湿热型用自制黄藤酒和痹症1号方治疗2周,寒湿型则用黄藤酒和痹症2号方治疗2周。对治疗前后的3组RA患者进行ESR、CRP、ASO、RF和抗-CCP检测。结果 3组RA患者治疗后ESR、RF和CRP水平明显下降,差异均有统计学意义(P<0.01或P<0.05);其中10例抗-CCP阳性RA者,治疗后抗-CCP水平也明显下降(P<0.01)。结论复方雷公藤制剂能够改善RA患者相关实验室指标,对活动期RA有较好的疗效。     

雷公藤对类风湿性关节炎患者外周血单个核细胞增殖和IL-6、TNF-α分泌的影响

目的探讨雷公藤治疗类风湿性关节炎（RA）的免疫作用机制。方法采用MTT比色法检测RA患者雷公藤处理前后PBMC的增殖活性，采用ELISA法测定RA患者雷公藤处理前后PBMC分泌的IL-6和TNF—α的含量。结果经雷公藤处理后，RA患者PBMC的增殖活性和产生的IL-6和TNF—α的含量均显著降低（P〈0．01），且在较高剂量时呈现明显的剂量-效应关系（20μl以上组的结果之间存在显著统计学意义P〈0．01）。结论雷公藤可能通过抑制RA患者PBMC的增殖活性和其IL～6、TNF—α的分泌能力，在RA的治疗中发挥其作用。     

Optimization of soy isoflavone extraction with different solvents using the simplex-centroid mixture design

The objective of this study was to optimize the extraction of different isoflavone forms (glycosidic, malonyl-glycosidic, aglycone and total) from defatted cotyledon soy flour using the simplex-centroid experimental design with four solvents of varying polarity (water, acetone, ethanol and acetonitrile). The obtained extracts were then analysed by high-performance liquid chromatography. The profile of the different soy isoflavones forms varied with different extractions solvents. Varying the solvent or mixture used, the extraction of different isoflavones was optimized using the centroid-simplex mixture design. The special cubic model best fitted to the four solvents and its combination for soy isoflavones extraction. For glycosidic isoflavones extraction, the polar ternary mixture (water, acetone and acetonitrile) achieved the best extraction; malonyl-glycosidic forms were better extracted with mixtures of water, acetone and ethanol. Aglycone isoflavones, water and acetone mixture were best extracted and total isoflavones, the best solvents were ternary mixture of water, acetone and ethanol.     

Lactobacillus GG bacteria ameliorate arthritis in Lewis rats

Probiotic bacteria have beneficial effects in infectious and inflammatory diseases, principally in bowel disorders. In the case of chronic progressive autoimmune arthritides, a major goal of treatment is to reduce inflammation. We hypothesized that probiotic bacteria would ameliorate inflammation found in arthritis models. To assess this effect, Lewis rats were injected with 50 microg bovine alpha-tropomyosin (TRM) or complete Freund's adjuvant (CFA) to induce tropomyosin arthritis (TA) or adjuvant arthritis (AA), respectively. In both models, the rats were divided into 6 groups and fed 0.5 mL/d of the following suspensions: 1) heat-killed Lactobacillus GG (LGG) bacteria; 2) live LGG, both 10(11) colony-forming units (cfu)/L; 3) sterilized milk; 4) plain yogurt; 5) yogurt containing 10(11) cfu/L LGG; or 6) sterilized water. In the disease-prevention experiments, feeding started 1 wk before or after disease induction. In the therapeutic experiments, feeding was initiated at the onset of clinical arthritis. In all experiments, there were significant interactions between time and treatment (P < 0.001), except for milk, which had no effect in the therapeutic experiment. Histologically, rats fed yogurt containing LGG had a milder inflammation in all experiments (P < 0.05), whereas rats fed plain yogurt exhibited a moderate inflammatory score only in the prevention experiments. Anti-TRM antibody titers were not affected by any of the treatments in any of the experiments. Ingestion of live or heat-killed human LGG had a clinically beneficial effect on experimental arthritis. Our observation of the remarkable preventive and curative effect on arthritis using commercial yogurts containing lactobacilli, especially LGG, suggests the need for investigation of these agents in arthritic patients.     

Inhibition of Ca(2+) channels in mouse spermatogenic cells by male antifertility compounds from Tripterygium wilfordii Hook. f

The male antifertility effect of a water-chloroform extract (GTW) from the root xylem of Tripterygium wilfordii has attracted worldwide interest. In the present study, by using whole-cell recording, the effects of GTW and two isolated monomers from GTW, demethylzeylasteral and L-epicatechin, on the T-type Ca(2+) channels in mouse spermatogenic cells were investigated. The results showed that each of them concentration-dependently and partially reversibly inhibited T-type Ca(2+) current in the cells. The IC(50) of GTW and demethylzeylasteral were approximate, while L-epicatechin inhibited the channels at a much higher concentration. The voltage dependence of the inhibitory effect and the changes in activation and inactivation time constants after application of these compounds were also examined. These data suggest that the inhibition of T-type Ca(2+) currents could be responsible for the antifertility activity of these compounds.     

补脾益肾清利法联合雷公藤多苷片治疗慢性肾小球肾炎临床研究

目的:研究分析慢性肾小球肾炎患者采用补脾益肾清利法联合雷公藤多苷片治疗的临床效果。方法:病例样本为76例慢性肾小球肾炎患者,随机分为研究组和对照组,n=38,对照组患者治疗方案为雷公藤多苷片,研究组患者治疗方案为补脾益肾清利法联合雷公藤多苷片,研究比较组间治疗效果。结果:评估组间临床治疗总有效率及肾功能指标,研究组均优于对照组(P<0.05)。评估组间治疗后24h尿蛋白定量、血β-MG数值,研究组均优于对照组(P<0.05)。评估组间不良反应发生率,无显著差异(P>0.05)。结论:慢性肾小球肾炎患者采用补脾益肾清利法联合雷公藤多苷片临床效果显著,值得推广应用。     

Evaluation of widely consumed botanicals as immunological adjuvants

BACKGROUND: Many widely used botanical medicines are claimed to be immune enhancers. Clear evidence of augmentation of immune responses in vivo is lacking in most cases. To select botanicals for further study based on immune enhancing activity, we study them here mixed with antigen and injected subcutaneously (s.c.). Globo H and GD3 are cell surface carbohydrates expressed on glycolipids or glycoproteins on the cell surface of many cancers. When conjugated to keyhole limpet hemocyanin (KLH), mixed with an immunological adjuvant and administered s.c. the magnitude of the antibody responses against globo H, GD3 and KLH depend largely on the potency of the adjuvant. We describe here the results obtained using this s.c. immunization model with seven botanicals purported to have immune stimulant effects. METHODS: Groups of 5-10 mice were immunized with globo H-KLH or GD3-KLH mixed with botanical, saline or positive control immunological adjuvant, s.c. three times at 1 week intervals. Antibody responses were measured 1 and 2 weeks after the 3rd immunization. The following seven botanicals and fractions were tested: (1) H-48 (Honso USA Co.), (2) Coriolus versicolor raw water extract, purified polysaccharide-K (PSK) or purified polysaccharide-peptide (PSP) (Institute of Chinese Medicine (ICM)), (3) Maitake extract (Yukiguni Maitake Co. Ltd. and Tradeworks Group), (4) Echinacea lipophilic, neutral and acidic extracts (Gaia Herbs), (5) Astragalus water, 50% or 95% ethanol extracts (ICM), (6) Turmeric supercritical (SC) or hydro-ethanolic (HE) extracts (New Chapter) or 60% ethanol extract (ICM) and (7) yeast beta-glucan (Biotec Pharmacon). Purified saponin extract QS-21 (Antigenics) and semisynthetic saponin GPI-0100 (Advanced BioTherapies) were used as positive control adjuvants. Sera were analyzed by ELISA against synthetic globo H ceramide or GD3 and KLH. RESULTS: Consistent significant adjuvant activity was observed after s.c. vaccination with the Coriolus extracts (especially PSK), a 95% ethanol extract of Astragalus and yeast beta-glucan, and (to a lesser extent) Maitake. Antibodies against KLH in all cases and against globo H in most cases were induced by these botanicals. Little or no adjuvant activity was demonstrated with H-48 or Echinacea extracts or the Astragalus water extract. Experiments with GD3-KLH as immunogen confirmed the adjuvant activity of the Coriolus, yeast beta-glucan and Astragalus extracts. While extraction with ethanol concentrated the active ingredients in Astragalus, it had no impact on Coriolus where the 90% ethanol precipitate and solute were equally active. CONCLUSIONS: Some, but not all, botanicals purported to be immune stimulants had adjuvant activity in our model. PSK and Astragalus were surprisingly active and are being further fractionated to identify the most active adjuvant components.