摘要
目的:探讨牛黄解毒片方中中药配伍能否减低雄黄的肝毒性及其与肝细胞凋亡的关系。方法:40只ICR小鼠随机分为雄黄组,牛黄解毒片全方组(7.8 g·kg^(-1)),牛黄解毒片全方去甘草黄芩大黄组(3.8 g·kg^(-1)),牛黄解毒片全方去雄黄组(7.3 g·kg^(-1))和正常组5组,雄黄组剂量设置为0.5 g·kg^(-1),根据《中国药典》的牛黄解毒片组方比例,设置其他给药组剂量(含等效雄黄量),各组经口给药9周,观察小鼠肝组织病理变化与氧化损伤,并应用末端转移酶标记技术(TUNEL)和免疫组化法检测肝细胞原位凋亡和凋亡相关分子Bcl-2和Bax的表达情况。结果:雄黄组小鼠肝组织出现显著水肿,且局部有坏死,而牛黄解毒片全方组及其他给药组的肝组织未见明显异常;与正常组比较,雄黄组的丙二醛(MDA)明显升高(P<0.05);TUNEL凋亡指数,Bax表达平均吸光度A明显增加,Bcl-2表达平均A明显减少(P<0.05);与雄黄组比较,牛黄解毒片全方组的MDA明显降低(P<0.05),TUNEL凋亡指数,Bax表达平均A明显下降,Bcl-2表达平均A明显增加(P<0.05);全方去甘草、黄芩、大黄后,凋亡指数较全方组增加,Bax表达亦明显增加,但Bcl-2表达无明显变化。结论:牛黄解毒片方中中药配伍可减低雄黄的肝毒性,抑制雄黄诱导的肝细胞凋亡可认为是牛黄解毒片配伍减低雄黄肝损伤的分子机制之一,抑制过程可能是通过促进Bcl-2表达而阻碍Bax表达来实现的,抑制药物与甘草、黄芩、大黄3味中药有关。
Objective： To explore the influence of Niuhuang Jiedu tablet compatibility on realgar hepatotoxicity and its relationship with apoptosis regulation. Method： Forty ICR mice were randomly divided into realgar group,Niuhuang Jiedu tablet whole prescription group（ 7. 8 g ·kg-1）,Niuhuang Jiedu tablet whole prescription excluding Glycyrrhizae Radix et Rhizoma,Scutellariae Radix and Rhei Radix et Rhizoma group（ 3. 8g·kg-1）,Niuhuang Jiedu tablet whole prescription excluding realgar group（ 7. 3 g·kg-1）,and normal group. The dose of realgar group was set to 0. 5 g·kg-1,and doses of other groups were set（ including the equivalent amount of realgar） according to the prescription ratio of Niuhuang Jiedu tablet in Chinese pharmacopoeia. Mice were administrated by oral for 9 weeks,then their pathological changes and oxidative damages in liver tissues were observed,and the terminal transferase labeling（ TUNEL） and immunohistochemical methods were used to detect the hepatocyte apoptosis and the expression of apoptosis-related molecules in situ Bcl-2 and Bax. Result：Significant edema and local necrosis were found in liver tissue of realgar group mice,but the whole prescription group and other administration groups showed no significant abnormalities. Compared with the normal group,malondialdehyde（ MDA） level was decreased was significantly increased in realgar group（ P 〈 0. 05）. TUNEL apoptosis index and the average optical density for expression of Bax were increased significantly,while the average optical density for expression of Bcl-2 was significantly decreased（ P 〈 0. 05）. Compared with the realgar group,MDA level（ P 〈 0. 05）, TUNEL apoptosis index and the average optical density for expression of Bax were significantly decreased in Niuhuang Jiedu tablet whole prescription group,while the average optical density for expression of Bcl-2 was significantly increased（ P 〈 0. 05）. TUNEL apoptosis index was increased in whole prescription excluding Glycyrrhizae Radix et Rhizoma,Scutellariae Radix and Rhei Radix et Rhizoma compared with the whole prescription,Bax expression was also increased significantly,but Bcl-2 expression had no apparent changes. Conclusion： The compatibility for Niuhuang Jiedu tablet could decrease the hepatotoxicity induced by realgar,and inhibiting hepatocyte apoptosis may be one of its mechanisms,and such inhibition may be achieved by promoting Bcl-2 expression and inhibiting Bax expression. The inhibition drugs may be associated with Glycyrrhizae Radix et Rhizoma,Scutellariae Radix,Rhei Radix et Rhizoma in the whole prescription.
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2015年第24期79-83,共5页
Chinese Journal of Experimental Traditional Medical Formulae
基金
国家自然科学基金青年基金项目(81201187)
江苏省高校自然科学基金项目(11KJD360001)
江苏省高校优势学科建设工程资助项目
关键词
牛黄解毒片
雄黄
凋亡调控
配伍
肝损伤
Niuhuang Jiedu tablet
realgar
apoptosis regulation
compatibility
hepatotoxicity
