坚龙胆抗炎活性部位筛选及抗炎机制探讨

Anti-inflammatory Effect and Mechanism Sduty of Effective Fractions from Gentiana rigescens

目的:筛选坚龙胆抗炎作用的活性部位,并研究其抗炎机制。方法:分别选用ICR小鼠180只,随机分为18组,分别为正常组,模型组,醋酸地塞米松组(5mg·kg-1),坚龙胆乙醇粗提物、石油醚、乙酸乙酯、正丁醇、水各层低、中、高剂量组(6,3,1.5g·kg-1),除正常组外,采用二甲苯致小鼠耳肿胀模型、冰醋酸致小鼠腹腔毛细血管通透性模型,分别ig给予相应药物,正常组和模型组给予等体积的5%聚山梨酯-80,每天1次,连续7d,检测小鼠的耳肿胀度及小鼠腹腔毛细血管通透性。取180只SD大鼠,同上方式分组及给药,采用角叉菜胶致大鼠足跖肿胀造模,进行抗炎活性筛选;另取大鼠50只,随机分为5组,分别为空白组,模型组,阳性药醋酸地塞米松组(5mg·kg-1),乙醇粗提物组(6g·kg-1),水部位组(6g·kg-1)。每日ig1次,连续7d,采用角叉菜胶致大鼠胸腔炎症造模,测定胸膜炎大鼠胸腔渗出液丙二醛(MDA),前列腺素E2(PGE2),肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)含量以及肺组织一氧化氮(NO),PGE2,TNF-α,IL-1β和MDA含量。结果:与模型组比较,各模型组小鼠耳廓肿胀、小鼠腹腔毛细血管通透性、大鼠足跖肿胀、大鼠胸腔及肺组织的炎症因子NO,PGE2,TNF-α,IL-1β,MDA均明显增高(P<0.01);与空白组比较,水部位高、中剂量(6,3g·kg-1)对二甲苯致小鼠耳廓肿胀,急性炎症导致的腹腔毛细血管通透性,角叉菜胶引起的大鼠足跖肿胀均有显著抑制作用(P<0.05,P<0.01),其余部位活性弱或基本无活性,坚龙胆水部位组(6g·kg-1)能抑制胸腔液MDA,PGE2,TNF-α,IL-1β含量升高(P<0.01),坚龙胆水部位组(6g·kg-1)能抑制肺组织NO,MDA,PGE2,TNF-α,IL-1β含量升高(P<0.01)。结论:坚龙胆水部位为抗炎活性部位,抗炎机制可能与影响炎症介质产生和抗氧化作用有关。

Objective ： To screen the anti-inflammatory fractions of Gentiana rigescens, and to explore its mechanism. Method： The ear edema model induced by xylene and inflammatory exudates model in the abdominal cavity induced by acetic acid in mice, foot swelling and chest infection model caused by carrageenan in rats were applied to screen the anti-inflammatory effect. The ear edema, inflammatory exudates and foot swelling experiments included the normal group, the model group, the dexamethasone acetate group, the different Fractions of G. rigescens groups. The chest infection experiment included the normal group, the model group, the dexamethasone acetate group, the water and ethanol extract of G. rigescens groups. The anti-inflammatory mechanisms were investigated by detecting the contents of malondialdehyde （ MDA）, prostaglandins （ PGE2） , tumor necrosis factor- alpha （TNF-α）, interleukin-lfl （IL-1β） in exudates, and the contents of nitric oxide （NO）, PGE=, TNF-α, IL- 1β, MDA in lung tissue. Result： Compared with the normal group, the contents of NO, PGE2, TNF-α, IL-1β, MDA increased in the ear edema, inflammatory exudates, foot swelling and chest infection groups （P 〈 0. 01 ）. Compared to the model group, the high-and middle-dose water extracts （6, 3 g ·kg-1） had a significant inhibition on all kinds of animal models （P 〈0.05, P 〈0. 01 ） , and the other extraction had a litter or no activity. The water extraction of Gentiana rigescens of all dose groups reduced the levels of MDA, PGE2 , TNF-α, IL-1β in exudates （P 〈 0.01 ）, and reduced the contents of NO, MDA, PGE2, TNF-α, IL-1β in lung tissue significantly （P 〈 0.01 ）. Conclusion ： Water fraction may be the anti-inflammatory active site of Gentiana rigescens. The effect may be related to the inhibition of the generation of mediators of inflammation and its antioxidation.