山豆根水提组分对实热证小鼠抗炎及伴随毒副作用机制研究

摘要

Objective To preliminarily study he mechanisms of anti-inflammatory efficacy and accompanied toxicity and side effects of water extraction components of Sophorae tonkinensis Radix et Rhizoma on throat excess-heat syndrome model in mice, discuss the relationship of "efficacy-syndrome-toxicity", provide experimental basis for reasonable application of Sophorae tonkinensis Radix et Rhizoma under the background of syndrome. Methods The method of throat excess-heat syndrome model in mice was built, which were administrated with different doses of water extraction components of Sophorae tonkinensis Radix et Rhizoma, detecting the level of PGE2, MDA, SOD, NO, NOS, GSH and GSH-Px in serum. Results Water extraction components of Sophorae tonkinensis Radix et Rhizoma had strong inhibitory effect on the croton oil inducing ear swelling in throat excess-heat syndrome mice after multiple administration. The level of PGE2 in serum obviously decreased after 3 d administration. The activity of MDA enhanced and SOD decreased. The levels of NO and NOS enhanced. The activity of GSH and GSH-Px decreased. All the changes were aggravated in accordance with the dosages, showing a certain dose-dependence relationship. Conclusion The anti-inflammation mechanism of water extraction components of Sophorae tonkinensis Radix et Rhizoma was mainly related with the reduction of the content of PGE2, and the level of SOD, MDA and NO in serum. The approach of accompanied hepatotoxioity damage was related with the oxidative damage. Whether there are other mechanisms, it remains to be further researched.%目的：初步研究山豆根水提组分对咽喉实热证小鼠抗炎药效伴随毒副作用机制，并以此探讨山豆根“功效-证候-毒性”相关性，为在证候背景下合理应用山豆根提供实验依据。方法制备咽喉实热证小鼠模型，采用巴豆油致小鼠耳肿胀法，灌胃不同剂量山豆根水提组分，末次给药后检测血清中前列腺素E2（PGE2）水平，检侧血内丙二醛（MDA）含量、超氧化物歧化酶（SOD）活性、一氧化氮（NO）、一氧化氮合酶（NOS）、谷胱甘肽（GSH）和谷胱甘肽过氧化物酶（GSH-px）的含量和活性。结果山豆根水提组分连续多次给药对巴豆油所致实热证小鼠耳肿胀具有较强的抑制作用，给药3天后血中PGE2含量明显降低，可致血中MDA含量增加，同时SOD活性下降；血中NO含量增加， NOS活性升高；血中GSH含量下降，GSH-Px活性下降。上述各指标变化随剂量的增加而改变，呈现一定的剂量依赖关系。结论山豆根水提组分对实热证小鼠具有较强的抗炎作用主要与降低血中PGE2含量、调节体内SOD，MDA水平有关，同时伴随毒副作用机制主要与氧化损伤路径有关，是否还存在其他机制，还有待进一步研究。