“半夏反草乌”减弱抗炎效应及其减效机制

Research of Weaken Anti-inflammatory Effects and Reduced Effect Characterization on ‘Pinelliae Rhizoma anti Aconiti Kusnezoffii Radix'

目的:探讨反药配伍之中半夏减弱草乌抗炎效应的初步机制及其表征形式。方法:64只SD大鼠随机分为模型组,醋酸泼尼松组,草乌组,草乌与法半夏配伍9∶1组,3∶1组,1∶1组,1∶3组,1∶9组。醋酸泼尼松组按20 mg·kg-1ig,草乌组按生药量为0.6 g·kg-1ig,草乌与法半夏配伍9∶1组,3∶1组,1∶1组,1∶3组,1∶9组分别按生药量0.67,0.8,1.2,2.4,6.0 g·kg-1ig,模型对照组灌服等体积生理盐水,连续给药7 d。第7天给药1 h后,每只大鼠右足足跖皮内注射新鲜蛋清建立蛋清致大鼠足跖肿胀模型,尾静脉注射伊文思蓝(EB),ELISA法测定组织中EB含量,血清中白细胞介素-1(IL-1),前列腺素E2(PGE2),肿瘤坏死因子-α(TNF-α)含量,观察草乌与不同比例法半夏配伍对足跖肿胀程度、血管通透性及炎症介质释放影响的差异;经Graph Pad Prism 5软件做四参数Hill拟合方程,评判影响足跖肿胀度较密切相关的指标。结果:与模型组比较,草乌组、草乌与法半夏各配伍组均可明显降低大鼠足肿胀程度和组织中的EB含量及血清中IL-1,PGE2,TNF-α的含量;各配伍组与草乌组比较,草乌组的抗炎作用最强(P<0.05),而草乌与法半夏配伍组(9∶1,3∶1,1∶1,1∶3,1∶9)的抗炎作用随法半夏用量增加而依次减弱;血清IL-1,PGE2,TNF-α含量与足跖肿胀度相关性均较好,组织中EB含量与之相关性较差。结论:法半夏可降低乌头的抗炎活性,该作用随法半夏用量的增加逐渐增强;"半夏反草乌"中的降效作用机制可能与法半夏可对抗乌头增加炎症介质生成、增加毛细血管通透性有关;血清PGE2含量与肿胀程度相关性较好且是直接参与炎症反应的介质,故可将其作为表征半夏反草乌中减弱抗炎效应的指标。

Objective： To investigate the preliminary mechanism and manifestations among the anti-drug compatibility of which Pinelliae Rhizoma weakened the anti-inflammatory effects of Aconiti Kusnezoffii Radix.Method： Sixty-four SD rats were randomly divided into model group, prednisone group, Aconiti Kusnezoffii Radix group,the Aconiti Kusnezoffii Radix and Pinelliae Rhizoma compatibility 9 ∶ 1 group,3 ∶ 1 group,1 ∶ 1group,1∶ 3 group,1∶ 9 group. The prednisone group was given at dose of 20 mg·kg- 1by gavage,the Aconiti Kusnezoffii Radix group was given at dose of 0. 6 g·kg- 1by gavage,the Aconiti Kusnezoffii Radix and Pinelliae Rhizoma compatibility 9∶ 1 group,3 ∶ 1 group,1 ∶ 1 group,1 ∶ 3 group,1 ∶ 9 group were given at dose of 0. 67,0. 8,1. 2,2. 4,6. 0 g·kg- 1by gavage,the model group were treated with the same volume＇s physiological saline for 7 days. An hour after administration on the 7th day,the egg-white was injected into the rats right paw to establish the egg-white induced rat paw edema model. Rat＇s tail vein injection of Evans blue（ EB）, and determination of tissue EB,serum interleukin-1（ IL-1）,prostaglandin E2（ PGE2）,tumor necrosis factor-α（ TNF-α） content by ELISA,study the difference of paw swelling degree,vascular permeability and the release of inflammatory mediators between Aconiti Kusnezoffii Radix and different proportions of Pinelliae Rhizoma. By Graph Pad Prism 5 software to do a four-parameter fit equation of Hill,and judge the impact indicators which was more closely related to paw swelling. Result： Compared with the model group,Aconiti Kusnezoffii Radix group,Aconiti Kusnezoffii Radix and Pinelliae Rhizoma compatibility group could significantly reduce the extent of rat＇s paw edema and the EB content in tissue, and the content of IL-1, PGE2,TNF-α in serum. The Aconiti Kusnezoffii Radix group compared with the Aconiti Kusnezoffii Radix and various proportions of Pinelliae Rhizoma compatibility group,Aconiti Kusnezoffii Radix group showed the strongest anti-inflammatory action（ P〈0. 05）.The Aconiti Kusnezoffii Radix and Pinelliae Rhizoma compatibility group（ 9 ∶ 1,3 ∶ 1,1 ∶ 1,1 ∶ 3,1 ∶ 9） of antiinflammatory effects was weakened in turn of the increase of the amount of Pinelliae Rhizoma. The content of IL-1,PGE2,TNF-α in serum were in good correlation with the paw swelling,but the content of EB in the tissue was to the opposite. Conclusion： Pinelliae Rhizoma can reduces the anti-inflammatory activity of Aconiti Kusnezoffii Radix,and the inhibitory effect increased with the amount gradually increase of Pinelliae Rhizoma. The content of PGE2 in serum had a better correlation with the degree of swelling, and are directly involved in inflammatory reaction medium,so it can be the indicator of Pinelliae Rhizoma which weakens the anti-inflammatory effect of Aconiti Kusnezoffii Radix.