大叶胡枝子根皮抗炎镇痛活性部位及其机制北大核心CSCD

筛选大叶胡枝子根皮抗炎镇痛作用的活性部位,并探讨其作用机制。采用二甲苯致小鼠耳肿胀、蛋清致大鼠足跖肿胀以及大鼠棉球肉芽肿炎症模型,考察大叶胡枝子根皮抗炎作用的活性部位,采用热板和醋酸扭体疼痛模型,考察大叶胡枝子根皮镇痛作用的活性部位,并检测活性部位对蛋清致炎模型大鼠血清的TNF-α、IL-1β和足跖炎性组织的PGE_2含量以及醋酸致痛模型小鼠血清的NO、MDA和PGE_2含量,以初步探究其抗炎镇痛作用机制。结果表明:大叶胡枝子根皮石油醚萃取部位明显抑制二甲苯所致小鼠耳肿胀和蛋清所致大鼠足跖肿胀以及棉球肉芽肿,明显延长热板所致小鼠痛阈值和明显减少醋酸所致小鼠扭体反应次数;明显减少蛋清致炎大鼠血清TNF-α、IL-1β及足跖炎性组织PGE_2含量,明显降低醋酸致痛小鼠血清NO、MDA和PGE_2含量。结果显示,大叶胡枝子根皮抗炎镇痛作用的活性部位主要为石油醚部位,其抗炎机制可能与减少炎症时TNF-α、IL-1β和PCE_2的产生有关,其镇痛作用机制可能与降低疼痛时NO、MDA和PGE_2的含量有关。     

大叶胡枝子根皮抗炎镇痛活性部位及其机制

筛选大叶胡枝子根皮抗炎镇痛作用的活性部位,并探讨其作用机制。采用二甲苯致小鼠耳肿胀、蛋清致大鼠足跖肿胀以及大鼠棉球肉芽肿炎症模型,考察大叶胡枝子根皮抗炎作用的活性部位,采用热板和醋酸扭体疼痛模型,考察大叶胡枝子根皮镇痛作用的活性部位,并检测活性部位对蛋清致炎模型大鼠血清的TNF-α、IL-1β和足跖炎性组织的PGE_2含量以及醋酸致痛模型小鼠血清的NO、MDA和PGE_2含量,以初步探究其抗炎镇痛作用机制。结果表明:大叶胡枝子根皮石油醚萃取部位明显抑制二甲苯所致小鼠耳肿胀和蛋清所致大鼠足跖肿胀以及棉球肉芽肿,明显延长热板所致小鼠痛阈值和明显减少醋酸所致小鼠扭体反应次数;明显减少蛋清致炎大鼠血清TNF-α、IL-1β及足跖炎性组织PGE_2含量,明显降低醋酸致痛小鼠血清NO、MDA和PGE_2含量。结果显示,大叶胡枝子根皮抗炎镇痛作用的活性部位主要为石油醚部位,其抗炎机制可能与减少炎症时TNF-α、IL-1β和PCE_2的产生有关,其镇痛作用机制可能与降低疼痛时NO、MDA和PGE_2的含量有关。     

虎杖苷对类风湿关节炎大鼠的治疗机制探究北大核心CSCD

探讨虎杖苷对类风湿关节炎(RA)大鼠的治疗作用及其可能作用机制。采用大鼠右后足趾皮内注射0. 1 m L完全弗氏佐剂致炎制备RA模型,分别给予160、80、40 mg/kg的虎杖苷混悬液灌胃,每日1次,造模后第28 d,对RA大鼠关节炎评分和足爪肿胀评分进行评估,并观察大鼠踝关节的病理学变化。检测血清TNF-α、IL-1β水平及关节滑膜组织中的Bax、caspase-3、Bcl-2、Wnt4、GSK-3β、β-catenin mRNA的表达及Wnt4、GSK-3β、β-catenin蛋白的表达。结果表明虎杖苷可显著降低RA大鼠的关节炎评分和足爪肿胀评分,改善关节腔炎症状态,降低血清TNF-α及IL-1β水平及FLS中的Wnt4、GSK-3β、β-catenin mRNA和蛋白及Bcl-2 mRNA的表达,并升高FLS中Bax、caspase3 mRNA的表达。虎杖苷可有效抑制RA大鼠滑膜增殖,促进滑膜细胞凋亡,控制关节炎症状态,其机制可能与抑制Wnt/β-catenin信号通路的激活有关。     

虎杖苷对类风湿关节炎大鼠的治疗机制探究

探讨虎杖苷对类风湿关节炎(RA)大鼠的治疗作用及其可能作用机制。采用大鼠右后足趾皮内注射0. 1 m L完全弗氏佐剂致炎制备RA模型,分别给予160、80、40 mg/kg的虎杖苷混悬液灌胃,每日1次,造模后第28 d,对RA大鼠关节炎评分和足爪肿胀评分进行评估,并观察大鼠踝关节的病理学变化。检测血清TNF-α、IL-1β水平及关节滑膜组织中的Bax、caspase-3、Bcl-2、Wnt4、GSK-3β、β-catenin mRNA的表达及Wnt4、GSK-3β、β-catenin蛋白的表达。结果表明虎杖苷可显著降低RA大鼠的关节炎评分和足爪肿胀评分,改善关节腔炎症状态,降低血清TNF-α及IL-1β水平及FLS中的Wnt4、GSK-3β、β-catenin mRNA和蛋白及Bcl-2 mRNA的表达,并升高FLS中Bax、caspase3 mRNA的表达。虎杖苷可有效抑制RA大鼠滑膜增殖,促进滑膜细胞凋亡,控制关节炎症状态,其机制可能与抑制Wnt/β-catenin信号通路的激活有关。     

活络效灵丹抗炎镇痛作用的实验研究

目的：研究活络效灵丹的抗炎、镇痛、消肿等药理作用,为该药的临床研究提供基础。方法：用二甲苯致小鼠耳肿胀法和角又莱胶致大鼠足肿胀法研究抗炎作用,用热板法和扭体法研究镇痛作用。结果：活络效灵丹能较好地抑制二甲苯引起的小鼠耳廓炎性肿胀和大鼠甲醛致足跖肿胀,能显著提高热板试验小鼠的痛阈,有效抑制冰醋酸引起的小鼠扭体反应次数。结论：活络效灵丹具有良好的抗炎、镇痛、消肿等作用。     

杨桃水提物对小鼠抗炎镇痛作用研究

为了研究杨桃水提物(Averrhoa caramhola L. water extract, AWE)对小鼠的抗炎、镇痛作用,采用蛋清致小鼠足跖肿胀和二甲苯致小鼠耳廓肿胀来建立炎症模型,通过比较致炎侧小鼠足跖、耳廓与非致炎侧小鼠足跖、耳廓的质量关系来观测AWE的抗炎作用,采用热板法观测其镇痛作用。将90只小鼠采用完全随机设计分组法分成3组:空白对照组、阿司匹林组及杨桃水提物组,每组30只,分别进行抗炎和镇痛系列判定试验。其中杨桃水提物组给予AWE(10.00 g/kg)灌胃、阿司匹林组给予阿司匹林(0.20 g/kg)灌胃、空白对照组给予相同体积蒸馏水灌胃,均每天1次,连续给药7 d。各组在末次给药后分别进行抗炎镇痛作用的观测。试验结果与空白对照组相比较后显示,AWE可明显抑制蛋清所致小鼠足肿胀、抑制二甲苯所致小鼠耳廓的肿胀度,可提高热板所致小鼠痛阈值(p0.05,p0.01),因此AWE具有明显的抗炎镇痛作用。     

姜黄素下调脊髓Toll样受体4及下游细胞因子减弱大鼠神经病理性痛

观察鞘内注射姜黄素对坐骨神经慢性压迫性损伤(CCI)大鼠痛阈和脊髓组织Toll样受体4(TLR4)及TNF-α、IL-1β和IL-10表达的影响．鞘内置管的120只大鼠随机均分为4组：假手术组(Sham),CCI组,溶剂对照组(SC),姜黄素治疗组(Cur,100 μg/天),建立CCI大鼠疼痛模型,术后第1、3、7、10和14天鞘内给药并测定痛阈,第3、7天取腰段脊髓第4～6节段(L4～L6)以Real-time PCR与Western blotting方法检测TLR4、HMGB1 mRNA和蛋白质的表达,ELISA法观察脊髓组织中TNF-α、IL-1β及IL-10表达变化．与Sham组相比,CCI组大鼠机械性痛阈与热痛阈显著降低(均P<0.05),同时脊髓组织TLR4、HMGB1 mRNA和蛋白质的表达明显增加(均P<0.05),TNF-α、IL-1β与IL-10的含量也明显升高(均P<0.05);鞘内注射姜黄素明显降低脊髓TLR4、高迁移率族蛋白1(HMGB1),TNF-α和IL-1β的表达,显著升高脊髓IL-10的表达,同时明显改善CCI大鼠疼痛行为(P<0.05)．姜黄素减轻神经病理性疼痛可能与下调TLR4途径促炎症因子表达有关,抑制TLR4途径有望成为治疗神经病理性疼痛的新策略．     

高压氧处理抑制神经病理性疼痛大鼠炎性细胞因子的表达

目的观察高压氧(hyperbaric oxygen,HBO)对坐骨神经慢性结扎损伤(chronic constriction injury,CCI)神经病理性疼痛大鼠TNF-α,IL-1β,IL-6炎性因子的影响,探讨其镇痛机制。方法 30只SD大鼠随机分为假手术组(S),坐骨神经结扎组(CCI)和结扎后高压氧组(CCI+HBO)3组,CCI术后每天都进行疼痛行为学评分,并在术后7天,用ELISA及脊髓的免疫组织化学方法检测各组大鼠炎性因子的表达水平。结果 CCI大鼠的疼痛行为学评分明显降低,高压氧处理可改善CCI大鼠疼痛行为学评分;ELISA检测到CCI大鼠TNF-α、IL-1β和IL-6血清含量明显升高,高压氧处理可减少CCI大鼠TNF-α、IL-1β和IL-6血清含量的升高;免疫组织化学检测发现CCI大鼠脊髓背角Ⅰ、Ⅱ层内TNF-α、IL-1β、IL-6阳性神经元数量增加,高压氧处理的CCI大鼠脊髓背角Ⅰ、Ⅱ层内TNF-α、IL-1β、IL-6阳性神经元数量的增加明显少于单纯CCI小鼠。结论高压氧可以抑制炎性因子的表达,这可能与其缓解神经病理性疼痛有关。     

松节方提取物对炎症动物模型的抗炎作用及机制探讨

该文旨在评价松节方提取物(SJF)的抗炎镇痛作用,尤其是对关节炎的抑制作用,并初步探讨其作用机制。采用二甲苯诱导的小鼠耳肿胀模型、醋酸诱导的小鼠疼痛模型、鸡II型胶原(CCII)诱导的大鼠关节炎模型,观察松节方提取物的体内抗炎镇痛活性和抗关节炎的作用,检测大鼠血清TNF-α、INF-γ、IL-10、IL-1β含量,观察大鼠踝关节组织病理学变化。结果表明松节方提取物可减轻上述模型的炎症及疼痛症状,抑制CCII致关节炎大鼠滑膜组织炎性细胞浸润和滑膜组织增生,能显著降低关节炎大鼠血清TNF-α、INF-γ、IL-1β含量,升高血清IL-10含量。说明松节方提取物具有较好的抗炎镇痛作用,可明显抑制CCII所致大鼠关节炎,降低其关节组织损伤程度,其机制可能与调节炎症因子表达相关。     

长春七超临界提取物镇痛、镇静和抗炎作用的研究

研究长春七超临界提取物(SELB)的镇痛、镇静和抗炎作用。镇痛实验采用小鼠热板法和扭体法;镇静实验采用与戊巴比妥钠协同催眠法和小鼠自主活动法;抗炎实验采用大鼠足跖肿胀法和小鼠耳肿胀法。结果显示:SELB高、中、低剂量组均能显著提高热板致痛小鼠的痛阈和醋酸致痛小鼠的扭体抑制率;高、中剂量组与戊巴比妥钠有协同作用,能显著延长小鼠睡眠时间,高、中、低剂量组能显著减少小鼠自主活动次数;高、中剂量组能显著抑制蛋清致大鼠的足跖肿胀率,高、中、低剂量组均能显著抑制二甲苯致小鼠的耳肿胀度。SELB具有的镇痛、镇静和抗炎作用与长春七的功能主治及临床应用相符。     

Crocin reduces the inflammation response in rheumatoid arthritis

This study is to determine the role and mechanism of crocin in rheumatoid arthritis (RA). Totally 60 Wistar SD rats were randomly divided into control group, RA model group, methotrexate group, crocin high dose, middle dose, and low dose groups. The paw swelling degree, arthritis score, thymus and spleen index, the mRNA and protein levels of iNOS, and the serum content of TNF-α, IL-1β, and IL-6 were evaluated. Crocin treatment significantly alleviated the paw swelling of RA rats. The arthritis score in crocin treatment groups was significantly lower than that in RA model group. Additionally, the thymus index, but not the spleen index, declined remarkably in crocin treatment groups than in RA model group. Besides, crocin administration significantly reduced the iNOS production and the serum content of TNF-α, IL-1β, and IL-6. Crocin may exert potent anti-RA effects through inhibiting cytokine.     

Analysis of the expression of toll-like receptors 2 and 4 and cytokine production during experimental Leishmania chagasi infection

Toll-like receptors (TLRs) recognise pathogen-derived molecules and influence immunity to control parasite infections. This study aimed to evaluate the mRNA expression of TLRs 2 and 4, the expression and production of the cytokines interleukin (IL)-12, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-17, IL-10 and transforming growth factor (TGF)-β and the production of nitric oxide (NO) in the spleen of mice infected with Leishmania chagasi. It also aimed to evaluate any correlations between mRNA expression TLR2 and 4 and cytokines and NO production. Infection resulted in increased TLR2-4, IL-17, TNF-α and TGF-β mRNA expression during early infection, with decreased expression during late infection correlating with parasite load. IFN-γ and IL-12 mRNA expression decreased at the peak of parasitism. IL-10 mRNA expression increased throughout the entire time period analysed. Although TGF-β, TNF-α and IL-17 were highly produced during the initial phase of infection, IFN-γ and IL-12 exhibited high production during the final phase of infection. IL-10 and NO showed increased production throughout the evaluated time period. In the acute phase of infection, there was a positive correlation between TLR2-4, TNF-α, IL-17, NO, IL-10 and TGF-β expression and parasite load. During the chronic phase of infection, there was a positive correlation between TLR2-4, TNF-α, IL-17 and TGF-β expression and parasite load. Our data suggest that infection by L. chagasi resulted in modulation of TLRs 2 and 4 and cytokines.     

Titanium and zirconia particle-induced pro-inflammatory gene expression in cultured macrophages and osteolysis,inflammatory hyperalgesia and edema in vivo

Aims

The biological reaction to wear debris is critical to the osteolysis underlying aseptic loosening of joint prosthetic implants. In an attempt to reduce aseptic loosening, ceramics have been introduced. This study was designed to evaluate, compare and correlate the expression of Toll-like receptors (TLRs), their intracellular adaptors and proinflammatory cytokines in cultured macrophages challenged with titanium or zirconia particles, as well as particle-induced osteolysis in calvaria and hyperalgesia and edema in hind paw.

Main methods

TLRs and their adaptors were evaluated at the mRNA level by RT-PCR, and cytokine expression was evaluated at the mRNA and protein levels. Osteolysis and hyperalgesia and edema were evaluated in vivo, in calvaria and hind paw, respectively.

Key findings

Cultured macrophages challenged with zirconia or titanium particles expressed increased mRNA for TLRs 2, 3, 4 and 9, and their adaptors MyD88, TRIF and NF-κB and cytokines TNF-α, IL-1β and IL-6, which were also increased at protein level. Quantitative differences are evident and, in general, zirconia particle-induced pro-inflammatory gene expression was lower than that induced by titanium particles. In in vivo experiments, exposition to titanium or zirconia particles induced osteolysis in calvaria and hyperalgesia and edema in hind paw; however those induced by zirconia particles were significantly lower. There is a strong and positive correlation between the expressions of mRNA for TLR4, NF-κB, TNF-α, IL-1β and IL-6.

Significance

Collectively, our data suggest that zirconia ceramic particles are less bioactive than titanium particles.     

Angiotensin-(1–7) attenuates collagen-induced arthritis via inhibiting oxidative stress in rats

The present study was designed to investigate the anti-rheumatic effects and the mechanism of angiotensin (Ang)-(1–7) in rat models with collagen-induced arthritis (CIA). The CIA model was established using male Wistar rats by intradermal injection of bovine collagen-II in complete Freund's adjuvant at the base of the tail. The levels of angiotensin converting enzyme 2 (ACE2)/Ang-(1–7)/Mas receptor (MasR) were reduced in CIA rats. The attenuation of paw swelling and arthritis scores and improvement of indexes of spleen and thymus were done by Ang-(1–7) injection in CIA rats. The increased levels of inflammatory cytokines, such as interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ in the serum and hind paw were blocked by Ang-(1–7) administration. In addition, enhanced NADPH oxidase (Nox) activity, increased levels of superoxide anions and malondialdehyde (MDA), and weakened superoxide dismutase (SOD) activity, were all reversed by treatment with Ang-(1–7). Nox1 overexpression reversed the suppressing effects of Ang-(1–7) on paw swelling and arthritis scores in CIA rats. The Ang-(1–7)-induced improvement in spleen and thymus indexes in CIA rats was abolished by Nox1 overexpression. Nox1 overexpression reversed the inhibitory effects of Ang-(1–7) by increasing IL-1β, IL-6, TNF-α, and IFN-γ levels in the serum and hind paw of CIA rats. These results demonstrated that Nox1 increased the oxidative stress in arthritis, and Ang-(1–7) improved rheumatism in arthritis via inhibiting oxidative stress.

     

Total Glucosides of Peony Attenuates 2,4,6-Trinitrobenzene Sulfonic Acid/Ethanol-Induced Colitis in Rats Through Adjustment of Th1/Th2 Cytokines Polarization

The present study is to investigate effects of total glucosides of peony (TGP) on 2,4,6-trinitrobenzene sulfonic acid (TNBS)/ethanol-induced colitis in rats and to explore potential clinical use of TGP for treatment of inflammatory bowel disease. Sixty Sprague–Dawley rats were randomly grouped into normal controls, model controls, sulfasalazine (SASP) controls (100 mg/kg/day), and low, medium, and high-dose TGP groups (25, 50, and 100 mg/kg/day, respectively). 24 h following colonic instillation of TNBS, TGP, and SASP were given by gastric gavage three times a day for 7 days. Disease activity index (DAI), colon macroscopic damage index (CMDI), histopathological score (HPS), and myeloperoxidase (MPO) activity were evaluated. Levels of serum TNF-α, IL-1β, and IL-10 were measured by ELISA, and expression of TNF-α, IL-1β, and IL-10 mRNA and protein in colonic tissues was detected by RT-PCR and western blot, respectively. Compared with rats in the model controls, TGP (50 or 100 mg/kg/day)-treated rats with TNBS/ethanol-induced colitis showed significant improvements of DAI, CMDI, HPS, and MPO activity. Moreover, administration of TGP (50 or 100 mg/kg/day) decreased the up-regulated levels of serum TNF-α and IL-1β, and expression of TNF-α and IL-1β mRNA and protein in colonic tissues, and increased the serum IL-10 and colonic IL-10 mRNA and protein level. And there was no significant difference compared with administration of SASP (P > 0.05). TGP attenuates TNBS/ethanol-induced colitis in rats and its efficacy is similar to SASP, the potential mechanism might be related to the adjustment of Th1/Th2 cytokines polarization by decreasing pro-inflammatory cytokine TNF-α and IL-1β, and increasing anti-inflammatory cytokine IL-10.     

Escin exerts synergistic anti-inflammatory effects with low doses of glucocorticoids in vivo and in vitro

Escin, a natural mixture of triterpenoid saponins isolated from the seed of the horse chestnut (Aesculus hippocastanum), had been demonstrated to possess anti-edematous and anti-inflammatory effects. The present study was designed to investigate whether escin exhibits synergistic anti-inflammatory effects when combined with glucocorticoids. The carrageenan-induced paw edema and pleuritis in bilaterally adrenalectomized rats were used to investigate the anti-inflammatory effects of escin and glucocorticoid alone or combined. The carrageenan-induced paw edema was inhibited only when escin and corticosterone (Cort) were administered together. Co-administration of escin with Cort significantly reduced the volume of exudates and the number of white blood cells of exudates in bilaterally adrenalectomized rats with pleuritis, but treatment with escin or Cort alone at a suboptimal concentration did not show any effect on the pleuritis rats. After the murine macrophagic RAW264.7 cells stimulated by lipopolysaccharide (LPS), they were treated with escin, Cort or escin and Cort. Then nitric oxide (NO), tumor necrosis factor-α (TNF-α) and interleukin 1β (IL-1β) of cell culture supernatants were analyzed. Escin or Cort markedly reduced the content of NO, TNF-α and IL-1β secreted by LPS-stimulated RAW264.7 macrophage cells. The combination of suboptimal concentrations of escin with Cort, which alone could not markedly inhibit the release of inflammatory factors, inhibited the secretion of NO, TNF-α and IL-1β in LPS-stimulated RAW264.7 macrophage cells. The findings suggest escin can synergize with glucocorticoids to enhance their anti-inflammatory effect.     

Effects of exercise training on plasma cytokine and chemokine levels, and thermoregulation

Pyrogenic factors may include the proinflammatory cytokines such as interleukin (IL)-1β, IL-6, tumor necrosis factor-alpha (TNF-α), and IL-8 (chemokine). Exercise also causes cytokinemia that might result in pyrogenically mediated body temperature elevation. The aim of the present study was to determine the effect of exercise training on exercise-induced plasma concentrations of IL-1β, IL-6, TNF-α, and IL-8. Messenger RNA levels of these factors were also evaluated in peripheral blood leukocytes. We also observed the relationship between cykokines, chemokines, and sweating after exercise. Nine tennis athletes (n=9) and untrained sedentary control subjects (n=10) ran for 1 h at 75% intensity of VO_2max. Venous blood samples were analyzed for plasma concentrations and mRNA expression in leukocytes of cytokines and chemokine of interest. Sweat volume was calculated by measuring body weight changes. Leukocyte mRNA expression and plasma protein levels of IL-1β, IL-6, TNF-α, and IL-8 immediately increased after exercise in both groups, but to a much greater extent in the athletic group. However, mRNA expression and plasma protein level for IL-6 and TNF-α, unlike IL-1β and IL-8, decreased more quickly in the athletic group compared to the control group during the recovery period. Compared to the control group, greater sweat loss volumes, and lower body temperatures in athletic group were observed at all time points. In conclusion, exercise training improved physical capacity and sweating function so that body temperature was more easily regulated during and after exercise. This may due to improved production of specific cytokine and chemokine in sweating during exercise.