N-9,10-蒽醌-2-甲酰基苯丙氨酸治疗大鼠痛风性关节炎的作用及机制

目的 探究N-9,10-蒽醌-2-甲酰基苯丙氨酸(NAY)对尿酸钠(MSU)所致痛风性关节炎(GA)大鼠的作用及机制。方法 将雄性SD大鼠随机分为7组,每组8只,即正常组、模型组、NAY低(20 mg·kg^-1)、中(40 mg·kg^-1)、高剂量组(80 mg·kg^-1)、秋水仙碱组(0.8 mg·kg^-1)和别嘌呤醇组(10 mg·kg^-1),通过关节腔内注射MSU晶体建立大鼠急性GA模型,各组灌胃给药5 d,给药第3天造模。将原代培养的大鼠腹部巨噬细胞分成空白组、模型组、NAY组、MCC950组和联合给药组。软尺测量大鼠踝关节周长并计算大鼠关节肿胀度;检测大鼠血清尿酸(UA)、肌酐(CRE)和尿素氮(BUN)含量;HE染色观察大鼠踝关节滑膜组织病理切片;检测各组血清、关节滑膜和细胞上清液中肿瘤坏死因子-α(TNF-α)和白介素-1β(IL-1β)的含量;并检测各组关节滑膜和细胞中NOD样受体热蛋白结构域相关蛋白3(NLRP3)、凋亡相关斑点样蛋白(ASC)和半胱氨酸天冬氨...     

鸡矢藤提取物对尿酸钠晶体诱导大鼠急性痛风性关节炎影响的研究

目的:研究鸡矢藤提取物(EPS)对尿酸钠晶体诱导大鼠急性痛风性关节炎(GA)的影响。方法:采用尿酸钠晶体制备大鼠GA模型,用足爪容积测量仪测定造模后不同时间大鼠的踝关节肿胀度;观察造模24h后大鼠步态并进行行为学评分;以HE染色观察大鼠关节组织的病理学改变;采用放射免疫分析法测定大鼠关节组织中白介素1β(IL-1β)和肿瘤坏死因子α(TNF-α)的水平。结果:EPS能显著降低GA模型大鼠的踝关节肿胀度,改善其步态异常。病理组织学检查结果显示,EPS可减轻GA模型大鼠踝关节的组织水肿,减少关节组织炎性细胞浸润,以及改善滑膜增生等病理改变。放射免疫分析检测结果显示,EPS可显著降低GA大鼠滑膜组织中TNF-α和IL-1β的水平。结论:EPS对尿酸钠晶体诱导大鼠GA有显著的改善作用,其机制可能与抑制TNF-α和IL-1β水平有关。     

黄芩总黄酮对大鼠类风湿性关节炎的缓解作用及BCL10/MALT1信号通路的影响

摘要：目的:探讨黄芩总黄酮对大鼠类风湿性关节炎的缓解作用及B细胞淋巴瘤因子10（BCL10）/黏膜相关淋巴瘤易位基因1（MALT1）信号通路的影响。方法:90只SD大鼠随机分成5组:正常对照组、模型组、阳性对照组(依那西普,0.5 mg·kg-1)、黄芩总黄酮低、高剂量组(50,100 mg·kg-1),每组18只。除正常对照组外,其余各组建立类风湿性关节炎模型。建模成功后依那西普组和黄芩总黄酮组腹膜内施用相应药物(10 ml·kg-1),正常对照组和模型组给予等体积生理盐水,1次/d,连续给药4周。实验结束后,测定大鼠关节炎指数和踝关节肿胀度,观察大鼠踝关节滑膜结构病理变化,酶联免疫吸附（ELISA）法测定血清炎症因子,实时荧光定量逆转录-聚合酶链反应（RT-PCR）法及蛋白免疫印迹法（Western Blot）法测定踝关节滑膜BCL10、MALT1 mRNA和蛋白表达水平。结果:模型组滑膜增厚,中性粒细胞弥漫性浸润,形成血管翳;依那西普组及黄芩总黄酮高剂量组大鼠踝关节滑膜细胞结构正常,可见较少的炎性细胞,无血管翳形成。与模型组比较,依那西普组和黄芩总黄酮组大鼠关节炎指数、踝关节肿胀度、血清白细胞介素6（IL-6）、白细胞介素10（IL-10）、肿瘤坏死因子α（TNF-α）水平、踝关节滑膜中BCL10、MALT1 mRNA和蛋白表达水平显著降低（P<0.05）,且黄芩总黄酮低剂量组以上各指标与高剂量组及依那西普组比较差异有统计学意义（P<0.05）。结论:黄芩总黄酮能明显抑制炎症反应,对类风湿性关节炎具有缓解作用;其机制可能与黄芩总黄酮抑制大鼠踝关节滑膜BCL10、MALT1 mRNA和蛋白表达进而抑制BCL10/MALT1信号通路激活有关。     

双黄痛风胶囊抗痛风性关节炎作用研究

目的:研究双黄痛风胶囊(SHTF)抗痛风性关节炎的作用。方法:采用尿酸钠(MSU)建立大鼠及家兔痛风性关节炎模型,测定大鼠足肿胀程度,家兔关节滑膜液量、滑膜液中白细胞数及关节滑膜组织炎症病变程度,观察SHTF抗痛风性关节炎作用。结果:大鼠灌胃SHTF5、10、20g.kg-1,能显著减轻其足肿胀程度;家兔口服SHTF4、8、16g.kg-1,能显著减少其痛风性关节滑膜液量和滑膜液中白细胞数;家兔口服SHTF8、16g.kg-1,能显著减轻其关节滑膜组织炎症病变程度。结论:SHTF对MSU所致痛风性关节炎具有显著的保护作用。     

澳洲产红葡萄酒协同洋葱降血糖作用研究

目的研究葡萄酒与葡萄酒协同洋葱对糖尿病模型小鼠血糖的影响。方法用四氧嘧啶致糖尿病小鼠模型,分别观察葡萄酒与葡萄酒协同洋葱对糖尿病小鼠血糖、体质量和胰腺病理切片等的影响。结果葡萄酒与葡萄酒协同洋葱对四氧嘧啶致高血糖小鼠血糖有明显的降低作用,其中葡萄酒+洋葱小、大剂量组对四氧嘧啶致高血糖小鼠的血糖降低作用显著(P<0.05或P<0.01);糖尿病小鼠体质量降低明显,经处理后各组小鼠的体质量均显著增加(P<0.05或P<0.01);糖尿病小鼠的胰腺病理切片病变显著,经处理后各组小鼠的胰腺病理切片均修复良好。结论葡萄酒与葡萄酒协同洋葱对糖尿病模型小鼠具有降低血糖的作用。葡萄酒与葡萄酒协同洋葱对糖尿病模型小鼠的胰腺有保护和修复作用。     

白茅根多糖对IgA肾病大鼠肾组织学病变及血清白细胞介素2和6的影响

目的观察白茅根多糖对IgA肾病大鼠肾组织学病变及血清白细胞介素(IL)2、IL-6含量的影响。方法 50只大鼠随机分为正常对照组、模型组、白茅根多糖低剂量组、白茅根多糖高剂量组和地塞米松组,每组10只。复合免疫法建立IgA肾病大鼠模型,于造模后第9周起白茅根多糖高、低剂量组及地塞米松组分别给予白茅根多糖20 mg·kg-1·d-1、10 mg·kg-1·d-1或地塞米松2 mg·kg-1·d-1,灌胃4周。检测各组大鼠尿红细胞、24 h尿蛋白,血清肌酐(Scr)、尿素氮(BUN)、IL-2、IL-6水平,并观察大鼠肾脏病理学改变。结果大鼠IgA肾病模型造模成功,模型组电镜观察见电子致密物沉积、系膜细胞增生、足突融合明显;尿红细胞数、24 h尿蛋白、血Scr、BUN、IL-6水平、IgA沉积水平均高于正常对照组(P<0.05或P<0.01)。各治疗组与模型组比较,尿红细胞数、24 h尿蛋白水平,血Scr、BUN均明显下降(P<0.01),白茅根多糖高剂量组血清IL-2和IL-6水平低于模型组(P<0.05或P<0.01),肾脏组织病理学异常改善。结论白茅根多糖可改善IgA肾病大鼠肾功能、降低IgA在系膜区的沉积,降低血清IL-2和IL-6水平可能是其作用机制之一。     

新风胶囊对佐剂性关节炎模型大鼠的抗炎作用

目的:研究新风胶囊对佐剂性关节炎(AA)模型大鼠的抗炎作用。方法:取70只SD大鼠随机均分为正常对照组、模型对照(等容生理盐水)组、阳性对照中药[祛风止痛胶囊0.4 g(生药)/kg]组、阳性对照西药(来氟米特片2.1 mg/kg)组和新风胶囊低、中、高剂量[0.8、1.6、3.2 g(生药)/kg]组,依次记为A、B、C、D、E、F、G组,除A组外其余各组大鼠皮内注射弗氏完全佐剂复制AA模型,致炎第12天开始连续ig给药28 d。检测并计算各组大鼠给药前、后足趾肿胀度和关节炎指数,于末次给药24 h后检测各组大鼠血清及关节滑膜组织中白细胞介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)含量并观察踝关节组织病理学形态变化。结果:与A组比较,B组大鼠足趾肿胀度和关节炎指数升高,血清及关节滑膜组织中IL-1β、TNF-α含量增加,差异有统计学意义(P<0.01)。与给药前比较,C、D、E、F、G组大鼠足跖肿胀度和关节炎指数降低,差异有统计学意义(P<0.05)。与B组比较,C、D、E、F、G组大鼠足趾肿胀度和关节炎指数降低,血清及关节滑膜组织中IL-1β、TNF-α含量降低,差异有统计学意义(P<0.01或P<0.05)。B组大鼠踝关节组织出现滑膜增生、炎性细胞浸润;C、D、F、G组大鼠滑膜增生和炎症情况较B组均减轻。结论:新风胶囊对AA模型大鼠具有抗炎作用,其机制可能与促进滑膜细胞凋亡、抑制滑膜增生有关。     

广枣总黄酮对三氧化二砷诱导大鼠心肌损伤的作用研究

目的:探讨广枣总黄酮(total flavnoids of fructus choerospondiatis,TFFC)对三氧化二砷(Arsenic trioxide,ATO)诱导大鼠心肌损伤的保护作用.方法:采用灌胃5mg·kg-1 ATO溶液建立动物损伤模型.实验设为空白组、模型组(ATO 5mg·kg-1)、TFFC低剂量组(TFFC 15mg·kg-1+ATO 5mg·kg-1),TFFC中剂量组(TFFC 30mg·kg-1+ATO 5mg·kg-1)、TFFC高剂量组(60 mg·kg-1+ATO 5mg·kg-1),空白组大鼠灌胃给予相同体积的药物溶媒0.5％羧甲基纤维素钠(CMC-Na),连续灌胃2周.用药期间监测大鼠体重,2周后用10％水合氯醛将大鼠麻醉,用生物机能实验系统测定大鼠心电图变化;腹主动脉取血,测定大血清中磷酸肌酸激酶(CK)、天冬氨酸氨基转移酶(AST)、乳酸脱氢酶(LDH)的活力;处死大鼠取心脏称重,计算心体比;检测心肌组织中过氧化氢酶(CAT)、超氧化物歧化酶(SOD)的谷胱甘肽过氧化物酶(GSH-Px)的活力.结果:模型组大鼠体重及心体比显著降低(P<0.05),血清中CK、AST、LDH的活力显著升高(P<0.05),心肌组织中CAT、SOD、GSH-Px的活力显著下降(P<0.05);与模型组比较,TFFC各剂量组大鼠体重及心体比显著升高(P<0.05),血清中CK、AST、LDH的活力显著降低(P<0.05),心肌组织中CAT、SOD、GSH-Px的活力显著升高(P<0.05).结论:TFFC对ATO诱导大鼠心肌损伤具有显著的保护作用.     

鱼腥草素钠抗类风湿关节炎滑膜增殖作用的实验研究

目的研究鱼腥草素钠(SH)抗类风湿关节炎(RA)的滑膜增殖作用。方法 Wistar大鼠随机分成5组:对照组、模型组、SH 130 mg·kg-1组、SH 260 mg·kg-1组、SH 520 mg·kg-1组。建立大鼠胶原诱导的类风湿关节炎(CIA)模型,计数方法测定大鼠关节炎指数(AI),称重法比较大鼠的体重变化,HE染色法光镜观察关节病理形态学变化,酶联免疫法(ELISA)检测血清中细胞因子白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、血管内皮生长因子(VEGF)、PKA、c AMP水平及免疫组化检测滑膜细胞凋亡情况。结果SH干预组关节炎指数较模型组低,体重降低不明显,关节破坏较模型组轻,细胞因子水平较模型组明显减低,滑膜细胞凋亡较模型组明显(P<0.01)。结论 SH可以增加RA滑膜细胞的凋亡,降低CIA大鼠的AI及炎症因子的水平。     

豨莶草对大鼠佐剂型关节炎的治疗作用及机制研究

摘要：目的:通过佐剂型大鼠关节炎模型探讨豨莶草对类风湿关节炎的治疗作用及机制研究。方法:豨莶草药材粉碎后乙醇加热回流制成干浸膏。60只雄性大鼠随机分为6组:正常对照组、模型组、美洛昔康组(40.0 mg·kg-1)、豨莶草高、中、低剂量组(1.6,0.8,0.4 g·kg-1),每组10只。通过注射完全弗氏佐剂进行刺激,构建佐剂型关节炎模型,造模成功后美洛昔康和豨莶草组灌胃给药,模型组和正常对照组给予等体积生理盐水,1次/d,持续28 d。测量大鼠足跖肿胀度、脾脏脏器系数,HE染色观察关节滑膜组织病理变化,Western blot检测关节滑膜NLRP3炎性小体的表达,ELISA检测血浆白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、C反应蛋白（CRP）、干扰素-γ（IFN-γ）、白细胞介素18（IL-18）的表达。结果:与正常对照组比较,模型组大鼠足跖肿胀度和脾脏系数明显增大,关节滑膜内NLRP3蛋白表达及血浆IL-1β、IL-6、TNF-α、CRP、IFN-γ、IL-18明显升高（P<0.05）。与模型组比较,豨莶草各剂量组大鼠足跖肿胀度和脾脏系数明显减少,关节滑膜内NLRP3蛋白表达及血浆IL-1β、IL-6、TNF-α、CRP、IFN-γ、IL-18明显降低（P<0.05）。结论:豨莶草高、中剂量组均可能通过抑制NLRP3炎性小体的表达,从而抑制滑膜细胞增殖,调节炎性因子生成,进而抑制类风湿关节炎的炎性反应,以达到减轻关节损伤的作用。     

痛风颗粒抗炎降尿酸作用的实验研究

目的:通过痛风颗粒对大鼠痛风性关节炎及痛风性高尿酸血症防治作用的实验研究,初步探究其药效学作用。方法:采用微晶型尿酸钠(monosodium urate,MSU)致大鼠踝关节肿胀、足跖肿胀模型和尿酸(uric acid,UA)诱导大鼠高尿酸血症模型,测定大鼠足肿胀率、患肢压力及步态积分、血尿酸值、白细胞计数及肾脏重量系数。结果:痛风颗粒能有效抑制大鼠踝关节、足跖肿胀以及患肢压力和步态积分,并能显著改善高尿酸血症大鼠体内尿酸水平,高剂量痛风颗粒能明显抑制白细胞增生。结论:痛风颗粒具有抑制炎症及降低血清高尿酸的作用。     

Bee Venom Alleviated Edema and Pain in Monosodium Urate Crystals-Induced Gouty Arthritis in Rat by Inhibiting Inflammation

Bee venom (BV) acupuncture has anti-inflammatory and analgesic effects; therefore, it was used as a traditional Korean medicine for various musculoskeletal disorders, especially arthritis. In this study, we investigated the effect of BV on monosodium urate (MSU) crystal-induced acute gouty rats. An intra-articular injection of MSU crystal suspension (1.25 mg/site) was administered to the tibiotarsal joint of the hind paw of Sprague Dawley rats to induce MSU crystal-induced gouty arthritis. Colchicine (30 mg/kg) was orally administered 1 h before MSU crystal injection as a positive control, and BV (0.5 mg/kg) was injected into the tibiotarsal joint immediately after MSU crystal injection. The ankle thickness, mechanical allodynia, and expression of proinflammatory cytokines (TNF-α, IL-1β, IL6, COX2 and iNOS) and chemokines (MIP-1α, MIP-1β, MCP-1, GRO-α, MIP-2α) were then evaluated. BV reduced the expression of proinflammatory cytokines and chemokines, which are important mediators of MSU crystal-induced inflammatory responses. This anti-inflammatory effect was also confirmed histologically to attenuate synovitis and neutrophil infiltration. We demonstrated that BV markedly ameliorated ankle edema and mechanical allodynia in gouty rats. These results suggest that BV acupuncture is a potential clinical therapy for acute gouty management.     

Therapeutic properties of quercetin on monosodium urate crystal-induced inflammation in rat

Objectives Gouty arthritis is characterized by intense, acute inflammatory reactions that occur in response to articular deposits of monosodium urate crystals. In this study we have assessed the effects of the flavonoid, quercetin, on monosodium urate crystal‐induced inflammation in rats, an experimental model for gouty arthritis. Methods Gouty arthritis was induced by intra‐articular injection of monosodium urate crystal suspension inside the ankle joint of the rat right hind limb. Circumference was assessed at 2, 4, 8, 12, 24, and 48 h after monosodium urate crystal injection. Histopathological analysis of joint synovial tissue, inflammatory mediator levels, lipid peroxidation, and antioxidant status in serum, liver and joint synovial tissue were determined in control and monosodium urate crystal‐treated rats at the end of experiment. Key findings Quercetin treatment attenuated oedema in a dose‐dependent manner and decreased histological signs of acute inflammation in the treated animals. In addition, quercetin treatment suppressed leucocyte recruitment, decreased chemokine levels, decreased levels of the lipid peroxidation end‐product malondialdehyde, and increased antioxidant enzyme activity in treated rats. Conclusions These results indicated that quercetin exerted a strong anti‐inflammatory effect that may be useful for the treatment of acute gouty arthritis.     

孟鲁司特钠联合咳喘三伏贴对哮喘患儿血清IL-4和IFN-γ水平的影响及其机制

目的探讨孟鲁司特钠联合咳喘三伏贴穴位贴敷对哮喘患儿血清白介素-4(IL-4)和干扰素-γ(IFN-γ)水平的影响及其机制。方法将67例哮喘患儿按照治疗方法分为对照组(n=33)与观察组(n=34)。2组患儿均给予常规治疗,包括抗感染、镇咳以及布地奈德吸入等常规治疗方法进行治疗;在此基础上,对照组给予孟鲁司特钠,观察组在对照组基础上采用穴位贴敷咳喘三伏贴进行治疗。比较2组临床疗效、患儿治疗后相关临床症状积分、患儿治疗前后各项免疫指标水平、治疗前后血清IL-4及IFN-γ的水平变化。结果 (1)经治疗,观察组临床总有效率为94.12%,显著高于对照组(75.76%)(P<0.05);(2)观察组患儿哮喘发作情况、易感冒、盗汗及鼻塞、打喷嚏积分均显著低于对照组(P<0.05);(3)2组患儿治疗后IgE、CD8~+水平均显著低于治疗前(P<0.05~0.01),2组患儿治疗后CD3~+、CD4~+及CD4~+/CD8~+水平均显著高于治疗前(P<0.05~0.01);(4)2组患儿治疗后血清IL-4水平均显著低于治疗前(P<0.05,P<0.01),2组患儿治疗后血清IFN-γ水平均显著高于治疗前(P<0.05),且2组患儿治疗后血清IL-4及IFN-γ水平差异均具有统计学意义(P<0.05)。结论孟鲁司特钠联合哮喘三伏贴穴位贴敷能够显著改善患儿哮喘的临床症状及体征,其发挥疗效的机制可能与改善患儿机体免疫功能及血清中相关炎性因子(IL-4、IFN-γ)水平相关。     

Inhibition of Inducible Nitric Oxide Synthase Attenuates Monosodium Urate-induced Inflammation in Mice

The present study elucidated the effect of the selective inducible nitric oxide synthase (iNOS) inhibitor N(6)-(1-iminoethyl)-L-lysine (L-NIL) on monosodium urate (MSU) crystal-induced inflammation and edema in mice feet. L-NIL (5 or 10 mg/kg/day) was administered intraperitoneally 4 h before injection of MSU (4 mg) into the soles of mice hindlimb feet. Twenty-four hours after MSU injection, foot thickness was increased by 160% and L-NIL pretreatment reduced food pad swelling in a dose dependent manner. Pretreatment of 10 mg/kg/day L-NIL significantly suppressed the foot pad swelling by MSU. Plasma level of nitric oxide (NO) metabolites and gene expression and protein level of iNOS in feet were increased by MSU, which was suppressed by L-NIL pretreatment. Similar pattern of change was observed in nitrotyrosine level. MSU increased the gene expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1β and L-NIL pretreatment suppressed MSU-induced cytokines expression. The mRNA levels of superoxide dismutase and glutathione peroxidase1 were increased by MSU and L-NIL pretreatment normalized the gene expression. Phosphorylation of extracellular signal-regulated kinase 1/2 and p38 was increased by MSU, which was suppressed by L-NIL pretreatment. The mRNA levels of iNOS, TNF-α, and IL-1β were increased by MSU in human dermal fibroblasts, C2C12 myoblasts, and human fetal osteoblasts in vitro, which was attenuated by L-NIL in a dose dependent manner. This study shows that L-NIL inhibits MSU-induced inflammation and edema in mice feet suggesting that iNOS might be involved in MSU-induced inflammation.     

Preventive effect of dioscin against monosodium urate-mediated gouty arthritis through inhibiting inflammasome NLRP3 and TLR4/NF-κB signaling pathway activation: an in vivo and in vitro study

Journal of Natural Medicines - Monosodium urate (MSU)-mediated inflammation is closely related to gouty arthritis (GA). Dioscin, an active ingredient, has been reported to possess anti-inflammatory...