栀子与黄连解毒汤肝毒性的比较研究

Comparative study on hepatic toxicity of Gardeniae Fructus and Huanglian Jiedu decoction

目的:观察黄连解毒汤中其他药物与栀子合用对栀子肝毒性的影响及作用机制。方法:大鼠分别灌胃给予栀子及"黄连解毒汤"水煎液,剂量均10倍于临床用量,每天给药1次,3 d后测血清中丙氨酸氨基转移酶(ALT)、天门冬氨酸转氨酶(AST)、碱性磷酸酶(ALP)、总胆汁酸(TBA)。取肝脏,计算肝重指数。测定肝组织中超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量、谷胱甘肽过氧化物酶(GSH-PX)活性、肿瘤坏死因子-α(TNF-α)的含量。TUNEL法测肝组织中细胞凋亡;免疫组化法测肝组织中凋亡相关蛋白Bax,Bcl-2的表达。结果:栀子组与对照组相比,肝重指数显著增加;ALT,AST,ALP,TBA显著升高;SOD,SOD/MDA及GSH-PX显著降低,MDA,TNF-α含量显著升高;累积吸光度,凋亡指数,Bax,Bax/Bcl-2显著升高。黄连解毒汤组与栀子组相比,肝重指数显著减小;ALT,AST,ALP,TBA显著降低,SOD,SOD/MDA及GSH-PX显著升高,MDA,TNF-α含量显著降低;累积吸光度与凋亡指数显著降低;Bcl-2显著升高,Bax/Bcl-2显著降低。结论:栀子有一定的肝毒性,机制与炎症、氧化应激反应诱导肝细胞的坏死与凋亡有关;黄连解毒汤中除栀子外的其他中药可通过提高清除自由基酶的活性、抑制炎症反应拮抗栀子引起的肝细胞损伤而降低栀子的肝毒性。

Objective： To observe the effect of ingredients in Huanglian Jiedu decoction（HLJDT） combined with Gardeniae Fructus on the hepatic toxicity of Gardeniae Fructus and its mechanism.Method： Rats were given Gardeniae Fructus and HLJDT decoction at the dose of 10 times of clinical dosage for 3 days.Their ALT AST,ALP,TBA were detected,and their liver weight index was calculated.SOD activity,MDA content,GSH-PX activity,TNF-α content in hepatic tissues were determined.The cell apoptosis in liver tissue was determined by TUNEL,and the expressions of apoptosis related proteins Bax,Bcl-2 were measured by immunohistochemical method.Result： Compared with the normal control group,the Gardeniae Fructus group showed significant increase in the liver weight index,ALT,AST,TBA and ALP,notable decrease in SOD,SOD/MDA and GSH-PX,and remarkable rise in MDA,TNF-α concentration,accumulated optical density,apoptosis index,Bax and Bax/ Bcl-2.Compare with that in the Gardeniae Fructus group,the liver index,ALT,AST,TBA,ALP reduced obviously;SOD,SOD/MDA and GSH-PX markedly increased;MDA and TNF-α significantly reduced;the accumulated optical density and apoptosis index significantly reduced;and Bax/Bcl-2 was much lower in HLJDT group.Conclusion： The hepatic toxicity caused by Gardeniae Fructus may be related to inflammation,oxidative stress-induced hepatocyte necrosis and apoptosis.Other ingredients in HLJDT,apart from Gardeniae Fructus,can decrease the hepatic toxicity caused by Gardeniae Fructus by increasing the enzyme activity eliminating radicals and inhibiting hepatocyte injury caused by inflammatory reaction against Gardeniae Fructus.