雷公藤微囊的药效学研究

雷公藤微囊（５～１５ｍｇ·ｋｇ－１）对大鼠角叉菜胶足肿胀、棉球肉牙肿及大鼠佐剂性关节炎（ＡＡ）均有明显的抑制作用，并能抑制ＡＡ大鼠腹腔巨噬细胞产生的白细胞介素１（ＩＬ－１）和小鼠溶血素抗体生成。体外实验发现，雷公藤微囊对刀豆蛋白诱导的小鼠脾细胞增殖反应及脂多糖诱导的大鼠腹腔巨噬细胞产生的ＩＬ－１均具有剂量依赖性的抑制作用。提示雷公藤微囊不仅具有明显的抗炎作用，而且具有免疫抑制作用。     

灵芝对动物胶原蛋白性关节炎的作用

本文观察了灵芝对大鼠胶原蛋白性关节炎的作用。Ⅱ型胶原蛋白（ＣⅡ）１.５ｍｇ／只ｄ_０背部皮内注射，引发胶原蛋白性关节炎（ＣＩＡ）。酶联免疫吸附法测定血清抗 ＣⅡ抗体水平；［３Ｈ］－ＴｄＲ掺入法测定鼠腹腔巨噬细胞产生白细胞介素－１（ＩＬ－１）的活性；四甲基偶氮唑盐（比色法）测定鼠脾淋巴细胞培养上清中白细胞介素－２（ＩＬ－２）的活性。观测针对ＣＩＩ的皮肤迟发型变态反应和大鼠后足足肿改变水平。灵芝０.５ ｇ·ｋｇ~(－１)和１.０ ｇ·ｋｇ·ｄ~(－１)可抑制迟发型变态反应，灵芝１.０ ｇ·ｋｇ~(－１)·ｄ~(－１)可降低血清抗ＣⅡ抗体水平，恢复ＩＬ－２产生水平，但对大鼠后足足肿以及白细胞介素－１（ＩＬ－１）产生无明显改善作用。提示灵芝作为免疫调节剂，对大鼠ＣＩＡ的抗炎效果较弱，但对免疫异常指标具有改善作用。     

Effects of indometacin on joint damage in rat and rabbit

目的：研究吲哚美辛（Ｉｎｄ）对关节损伤的影响．方法：检测佐剂性关节炎大鼠（ＡＡ）非致炎侧后足爪容积，ＬＰＳ诱导腹腔巨噬细胞和关节滑膜细胞产生白细胞介素１（ＩＬ１），以及兔滑膜成纤维细胞增殖反应和软骨蛋白多糖的合成．结果：Ｉｎｄ２ｍｇ·ｋｇ－１·ｄ－１ｉｇ９ｄ，可抑制ＡＡ大鼠ｄ１８，ｄ２１，和ｄ２４继发炎症反应，但促进巨噬细胞和滑膜细胞分泌ＩＬ１．Ｉｎｄ１０μｍｏｌ·Ｌ－１体外分别促进ＩＬ１诱导兔滑膜成纤维细胞增殖反应以及抑制关节软骨蛋白多糖合成．结论：Ｉｎｄ不利于关节损伤的修复．     

氯苯扎利钠对正常大鼠及佐剂性关节炎大鼠IL－1活性及大鼠腹腔巨噬细胞H_2O_

研究了氯苯扎利钠（ＣＣＡ）对正常大鼠和佐剂性关节炎大鼠ＩＬ－１活性及大鼠腹腔巨噬细胞Ｈ＿２Ｏ＿２释放的影响。经ＣＣＡ（１０．２００μｇ／ｍｌ）作用后所制备的含ＩＬ－１上清液（正常大鼠腹腔巨噬细胞１．５×１０￣７／ｍｌ，ＬＰＳ８μｇ／ｍｌ）使小鼠胸腺细胞在体外增殖活性（［３￣Ｈ］ＴｄＲ参入法）降低。ＣＣＡ对佐剂性关节炎大鼠ｉｐ￣７天后可使升高的ＩＬ－１活性降低。采用酚红法测定Ｈ＿２Ｏ＿２释放，可见ＣＣＡ５～１００μｇ／ｍｌ对腹腔巨噬细胞Ｈ＿２Ｏ＿２释放抑制作用明显。这些结果表明，ＣＣＡ抗炎和治疗ＲＡ的机制之一可能是通过干扰ＲＯＳ的释放及抑制ＩＬ－１活性，使ＩＬ－１作为肽类炎症介质参与反应和参与免疫调节的过程受阻而达到的。     

白芍总甙,芍药甙和白芍总甙去除芍药甙对佐剂性关节炎大鼠…

福氏完全佐剂致炎后ｄ１８，佐剂性关节炎（ＡＡ）大鼠刀豆素Ａ（３ｍｇ．Ｌ＾－１）诱导的脾淋巴细胞增殖反应显著低于正常对照水平。脂多糖（６ｍｇ．Ｌ＾－１）诱导的大鼠腹腔巨噬细胞产生ＩＬ－１显著高于正常对照大鼠。结果表明上述三种药物均具有浓度和机理依赖性的双向免疫调节作用，ＴＧＰ的作用最强。     

松果体对正常及佐剂性关节炎大鼠免疫细胞的影响

采用松果体切除（ＰＸ）及腹腔注射外源性褪黑素（ＭＴ）的方法，观察松果体对正常及佐剂性关节炎（ＡＡ）大鼠免疫细胞的影响。结果发现，ＰＸ后，ＣｏｎＡ及ＬＰＳ诱导的淋巴细胞增殖反应在正常及ＡＡ大鼠明显降低；正常大鼠ＬＰＳ诱导的腹腔巨噬细胞产生的白细胞介素Ｉ（ＩＬ－１）减少，而ＡＡ大鼠的ＩＬ－１明显增加。ＭＴ（１０μｇ·ｋｇ－１）作用则与此相反，并能使ＰＸ引起的免疫指标的改变恢复正常。上述结果表明；松果体对免细胞的功能有调节作用。     

苦参碱对体外小鼠脾细胞增殖及腹腔巨噬细胞释放白细胞介素—1…

目的：研究苦参碱对小鼠脾细胞增殖及腹腔巨噬细胞释放白细胞介素－１（ＩＬ－１）及－６（ＩＬ－６）的影响，方法：（＾３Ｈ）ＴｄＲ参入法测定脾细胞增殖，胸腺细胞增殖法和Ｂ９细胞增殖ＭＴＴ法测定ＩＬ－１和ＩＬ－６活性。结果，苦对碱（１２５－５００ｍｇ．Ｌ＾－１）以剂量依赖方式显著抑制ＣｏｎＡ及脂多糖（ＬＰＳ）诱导的小鼠脾细胞增殖心及ＬＰＳ诱导的的小鼠腹腔巨噬细胞释放ＩＬ－２和ＩＬ－６。结论：苦参碱抑制体个     

白芍总甙、芍药甙和白芍总甙去除芍药甙对佐剂性关节炎大鼠的免疫调节作用

福氏完全佐剂致炎后ｄ１８，佐剂性关节炎（ＡＡ）大鼠刀豆素Ａ（３ｍｇ·Ｌ－１）诱导的脾淋巴细胞增殖反应显著低于正常对照水平，脂多糖（６ｍｇ·Ｌ－１）诱导的大鼠腹腔巨噬细胞（ＰＭΦｓ）产生ＩＬ－１显著高于正常对照大鼠。０．５～３１２．５ｍｇ·Ｌ－１白芍总甙（ＴＧＰ）、芍药甙（ＰＦ）和白芍总甙去除芍药甙（ＴＧＰ－ＰＦ）均能浓度依赖性地增强ＡＡ大鼠低下的脾淋巴细胞增殖反应（量效曲线均呈钟罩形），降低ＡＡ大鼠ＰＭΦｓ过度产生ＩＬ－１（量效曲线均呈倒钟罩形）。其中，２．５～６２．５ｍｇ·Ｌ－１ＴＧＰ的调节作用显著强于ＰＦ和ＴＧＰ－ＰＦ各等剂量组。这些结果表明，上述三种药物均具有浓度和机能依赖性的双向免疫调节作用，ＴＧＰ的作用最强。     

雷公藤多甙对大鼠佐剂性关节炎治疗作用和免疫机制的研究

利用大鼠佐剂性关节炎（ＡＡ）动物模型，研究了雷公藤多甙的治疗作用及其免疫机制。结果发现，雷公藤多甙能改善ＡＡ病情。雷公藤多甙治疗显效后，ＡＡ大鼠血清ＩＬ－１和ＩＬ－６水平明显降低，关节液内炎症细胞因子的水平下降，腹腔巨噬细胞及脾淋巴细胞分泌细胞因子的能力显著受到抑制。ＡＡ大鼠脾细胞增殖能力显著降低，雷公藤多甙治疗后对脾细胞增殖与ＡＡ对照组比较无明显差异。结果表明雷公藤多甙抗炎作用的发挥是通过免疫抑制作用而实现的。     

苦参碱对体外小鼠脾细胞增殖及腹腔巨噬细胞释放白细胞介素－1及－6的影响

目的：研究苦参碱对小鼠脾细胞增殖及腹腔巨噬细胞释放白细胞介素１（ＩＬ１）及６（ＩＬ６）的影响．方法：［３Ｈ］ＴｄＲ参入法测定脾细胞增殖，胸腺细胞增殖法和Ｂ９细胞增殖ＭＴＴ法测定ＩＬ１和ＩＬ６活性．结果：苦参碱（１２５－５００ｍｇ·Ｌ－１）以剂量依赖方式显著抑制ＣｏｎＡ及脂多糖（ＬＰＳ）诱导的小鼠脾细胞增殖以及ＬＰＳ诱导的小鼠腹腔巨噬细胞释放ＩＬ１和ＩＬ６．结论：苦参碱抑制体外小鼠脾细胞增殖及巨噬细胞分泌ＩＬ１和ＩＬ６．     

Interleukin-1 receptor antagonist intervenes in signaling between different types of synoviocytes in rats with adjuvant arthritis

AIM: To investigate the mechanisms of interleukin-1 receptor antagonist (IL-1ra) in the treatment of adjuvant arthritis (AA). METHODS: AA was induced in rats by treatment with Freunds complete adjuvant (FCA). Rats were given an intracutaneous injection of IL-1ra (2.5, 10, 40 mg/kg, 3 times per day) from d 14 to d 21 after immunization. Synoviocyte proliferation and the activity of IL-1 were determined by using MTT assay. Tumor necrosis factor alpha (TNF-alpha) and prostaglandin E(2) (PGE(2)) concentrations were measured by radioimmunoassay. The ultrastructure of synoviocytes was observed by using a transmission electron microscope. Phosphorylation of c-Jun N-terminal kinase (JNK), extracellular regulating kinase (ERK) and p38 kinase were detected by Western blot analysis. RESULTS: IL-1ra (10 and 40 mg/kg, ic, d 14-21) modulated the secondary inflammatory reaction (P < 0.01), ultrastructure of synoviocytes and mitogen-activated protein kinase (MAPK) phosphorylation in AA rats. The administration of IL-1ra (10 and 40 mg/kg, ic, d 14-21) in AA rats significantly decreased the production of IL-1, PGE2 and TNF-alpha by macrophage-like synoviocytes (MLS) (P < 0.01). IL-1ra (2.5 mg/kg) also decreased the production of PGE2 (P < 0.01) and TNF-alpha (P < 0.05) by MLS in AA rats. The increased phosphorylation of MAPK and cell proliferation in fibroblast-like synoviocytes (FLS) stimulated by supernatants of MLS in AA rats was also inhibited by IL-1ra (10 and 40 mg/kg, ic, d 14-21). CONCLUSION: IL-1ra has anti-inflammatory effects because it modulates the ultrastructure of synoviocytes, decreases the production of pro-inflammatory mediators by MLS, and inhibits the phosphorylation of MAPK in FLS.     

白细胞介素-1受体拮抗剂(IL-1ra)对大鼠佐剂性关节炎的影响

研究IL-1 ra（Interleukin-1 Receptor Antagonist）对大鼠佐剂性关节炎的治疗作用。采用SD大鼠作为受试动物，一侧足爪注射完全弗氏佐剂造成大鼠佐剂性关节炎（Adjuvant arthritis，AA）模型，检测足爪肿胀度、脾淋巴细胞增殖反应和腹腔巨噬细胞产生IL-1的水平。结果：IL-1 ra能明显减轻AA大鼠足肿胀程度；明显减少AA大鼠足爪评分分值；明显降低AA大鼠B淋巴细胞增殖反应和腹腔巨噬细胞IL-1的产生，可恢复降低的T淋巴细胞增殖反应。病理组织学观察结果表明，IL-1 ra可明显减轻AA大鼠关节中炎性细胞浸润、滑膜增生、血管翳形成、软骨和骨的破坏。IL-1 ra对AA有明显的治疗作用     

阿克他利对佐剂性关节炎大鼠腹腔巨噬细胞分泌IL-1和T淋巴细胞亚群的影响

Effects of actarit on production of interleukin-1（IL-1）by peritoneal macrophages from adjuvant arthritis(AA) rats ex vivo and the ratio of subpopulation of T lymphocytes in AA rats ex vivo and the production of hydrogen peroxide （H₂O₂）by peritoneal macrophages of mice in vitro were studied. The results showed that IL-1 synthesis from the adherent peritoneal macrophages induced with lipopolysaccharide (8 mg·L^-1) in AA rats in vivo were inhibited by actarit; the ratio of L₃T₄⁺/Lyt-2⁺ was lowered after administrating actarit; and H₂O₂ release of the peritoneal macrophages of mice was reduced in dose-dependent manner. The data suggest that the therapeutic effects of actarit on AA rats be related to inhibition of production of IL-1 and reduction of H₂O₂ release and lowered rat io of L₃T₄⁺/Lyt-2⁺ T-lymophocyte.     

Suppression of adjuvant arthritis by hesperidin in rats and its mechanisms

The citrus flavonoid hesperidin has been reported to possess a wide range of pharmacological properties. We have investigated the preventive and therapeutic effects of hesperidin on the development of adjuvant arthritis (AA), a rat model of rheumatoid arthritis (RA). Freund's complete adjuvant was used to induce AA in rats. Secondary paw swelling, polyarthritis index and histopathological assessment of ankle joints were used to evaluate the effects of hesperidin on AA rats. Concanavalin-A-induced T-lymphocyte proliferation and interleukin (IL)-2 production by splenocytes were measured using the MTT assay. Levels of IL-1, IL-6 and tumour necrosis factor (TNF)-alpha secreted by peritoneal macrophages (PM) were measured by RIA. Intragastric administration of hesperidin significantly attenuated secondary paw swelling and reduced the polyarthritis index of AA rats in a dose-dependent manner. In addition, hesperidin clearly ameliorated the pathological changes in AA rats. Hesperidin also restored the suppression of T-lymphocyte proliferation and IL-2 production, and downregulated production of IL-1, IL-6 and TNF-alpha by PM in AA rats. Our results suggest that hesperidin improves AA by downregulating the function of over-active macrophages and by up-regulating the activities of dysfunctional T lymphocytes. Hesperidin may therefore have therapeutic value for the clinical treatment of RA. Further research is required to clarify the detailed mechanisms of the protective effects of hesperidin on AA.     

吲哚美辛对大鼠和兔关节损伤的影响

AIM: To study the effects of indometacin (Ind) on joint damages. METHODS: The volume of noninjected hind paw and interleukin-1 (IL-1) production from peritoneal macrophages and articular synoviocytes induced by lipopolysaccharides were assayed in adjuvant arthritis (AA) rats. Measurements of synovial fibroblast proliferative response and proteoglycan synthesis of cartilage from rabbits were used. RESULTS: The secondary inflammatory reactions in AA rats on d 18, 21, and 24 were suppressed by i.g. Ind 2 mg.kg-1.d-1 for 9 d. Ind promoted IL-1 production from both macrophages and synoviocytes in AA rats. Ind 10 mumol.L-1 enhanced the proliferation of rabbit synovial fibroblasts and suppressed the proteoglycan synthesis of articular cartilage in response to IL-1 in vitro. CONCLUSION: Ind is unfavorable to the repair of joint destruction.     

来氟米特对佐剂性关节炎大鼠腹腔巨噬细胞IL—1，IL—6和TNF—α产生的动态影响

目的:探讨来氟米特(leflunomide,LEF)对佐剂性关节炎大鼠腹腔巨噬细胞IL-1,IL-6和 TNF-α分泌的影响及其抗炎、抗类风湿的可能作用机制.方法:大鼠足跖皮下注射Freund完全佐剂诱导关节炎模型;LEF灌胃后分次获取腹腔巨噬细胞,其培养上清液中IL-1,IL-6和TNF-α活性采用ELISA法或生物法测定.结果:佐剂性关节炎大鼠腹腔巨噬细胞IL-1,IL-6和TNF-α分泌较正常对照组明显升高;LEF对由 LPS诱导产生的 IL-1和 TNF-α有明显的抑制作用,作用产生快;LEF(10,25 mg/kg)在应用21天后对IL-6的分泌也有明显抑制作用.结论:来氟米特具有抑制佐剂性关节炎大鼠腹腔巨噬细胞 IL-1,IL-6和 TNF-α分泌水平的作用.     

Effects of esculentoside A on production of interleukin-1, 2, and prostaglandin E2

AIM: To investigate the influence of esculentoside A (EsA) on immunological function and its mechanism of antiinflammation. METHODS: Interleukin-1 production was measured by thymocyte co-stimulating assay; the radioactivity of [^3H]arachidonic acid (AA) was used to evaluate the release of AA; prostaglandin E2 production was measured with radioimmunoassay (RIA); IL-2 and IFN-γ were detected by ELISA method. RESULTS: EsA (3-12μmol/L)could potently inhibit the production of IL-1 and PGE2 from both silent and LPS induced macrophages.EsA had no significant effect on the release of AA from murine macrophages. EsA could inhibit the production of IL-2 from murine lymphocytes induced by ConA, but not affect the production from silent lymphocytes. EsA showed no effect on the production of IFN-γ from both silent and ConA induced lymphocytes. CONCLUSION:EsA could affect the immunological function through inhibiting the production of IL-2 from activated splenocytes and the inhibition of production of IL- 1 and PGE2 might be one of the anti-inflammation mechanisms of EsA.     

山香圆总黄酮体外对大鼠佐剂性关节炎免疫功能的影响

目的观察山香圆总黄酮(totalflavonoidsofturpiniaargutaseen,TFS)体外对佐剂性关节炎(adjuvantarthritis,AA)大鼠免疫功能的影响。方法选择健康♂SD大鼠,采用弗氏完全佐剂(freundscompleteadjuvant,FCA)诱导AA大鼠模型:将同一批号的的卡介苗80℃水浴1h灭活,用灭菌液体石蜡配成10g·L-1的乳剂。d28处死大鼠,取AA大鼠的免疫细胞(脾细胞和腹腔巨噬细胞)体外给药培养并检测一些免疫指标:细胞增殖法检测ConA、LPS诱导的大鼠脾淋巴细胞增殖反应及IL-1、IL-2的分泌水平;放免法检测PGE2水平。结果与正常组相比,AA大鼠ConA、LPS诱导的脾淋巴细胞增殖功能低下,脾淋巴细胞产生的IL-2活性下降,LPS诱导的大鼠腹腔巨噬细胞产生的IL-1、PGE2水平明显升高。TFS(10-8~10-4)mg·L-1可纠正AA大鼠低下的脾淋巴细胞增殖反应和脾细胞IL-2的产生,降低AA大鼠腹腔巨噬细胞产生过高的IL-1和PGE2。结论山香圆总黄酮对AA大鼠的异常免疫功能具有调节作用。     

白芍总甙对大鼠佐剂性关节炎及其免疫功能的影响

本文研究了白芍总甙(TGP)对大鼠佐剂性关节炎(AA)的治疗作用及其机理。TGP 50 mg·kg~1·d~1 ig,连续11d对大鼠多发性关节炎有明显的防治作用,同时可使AA大鼠腹腔巨噬细胞升高的H_2O_2和白细胞介素(IL-1)水平下降,并可使AA大鼠低下的胸腺细胞有丝分裂原反应及脾淋巴细胞产生IL-2能力恢复正常。表明TGP对AA大鼠有抗炎和机能依赖性的免疫调节作用。