Zhang Yu-Mei, Ren Hong-Yu, Zhao Xian-Lin, Li Juan, Li Jun-Yi, Wu Fu-Sheng, Su Hang, Tang Wen-Fu
Yu-Mei Zhang, Hong-Yu Ren, Juan Li, Jun-Yi Li, Wen-Fu Tang, Sichuan Provincial Pancreatitis Center, Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China.
World J Gastroenterol. 2017 Feb 28;23(8):1367-1374. doi: 10.3748/wjg.v23.i8.1367.
To explore the pharmacokinetics and pharmacodynamics of Da-Cheng-Qi decoction (DCQD) in the liver of rats with severe acute pancreatitis (SAP) based on an herbal recipe tissue pharmacology hypothesis.
Healthy male Sprague-Dawley rats were randomly divided into a sham operation group (SOG); a model group (MG); and low-, median- and high-dose treatment groups (LDG, MDG, and HDG, respectively). Different dosages (6, 12 and 24 g/kg for the LDG, MDG, and HDG, respectively) of DCQD were administered to the rats with SAP. The tissue concentrations of aloe-emodin, rhein, emodin, chrysophanol, honokiol, rheo chrysophanol, magnolol, hesperidin, naringenin and naringin in the liver of the treated rats were detected by high-performance liquid chromatography tandem mass spectrometry. Alanine transaminase (ALT) and aspartate transaminase (AST) in serum, inflammatory mediators in the liver and pathological scores were evaluated.
The major components of DCQD were detected in the liver, and their concentrations increased dose-dependently. The high dose of DCQD showed a maximal effect in ameliorating the pathological damages, decreasing the pro-inflammatory mediators tumor necrosis factor-α and interleukin (IL)-6 and increasing anti-inflammatory mediators IL-4 and IL-10 in the liver. The pathological scores in the pancreas for the MG were significantly higher than those for the SOG ( < 0.05). DCQD could reduce the pathological scores in the pancreas and liver of the rats with SAP, especially in the HDG. Compared to the SOG, the ALT and AST levels in serum were higher in the MG ( < 0.05), while there was no statistical difference in the MG and HDG.
DCQD could alleviate liver damage by altering the inflammatory response in rats with SAP based on the liver distribution of its components.
基于中药组织药理学假说，探讨大承气汤（DCQD）在重症急性胰腺炎（SAP）大鼠肝脏中的药代动力学和药效学。
将健康雄性Sprague-Dawley大鼠随机分为假手术组（SOG）、模型组（MG）以及低、中、高剂量治疗组（分别为LDG、MDG和HDG）。给SAP大鼠分别灌胃不同剂量的DCQD（LDG、MDG和HDG分别为6、12和24 g/kg）。采用高效液相色谱串联质谱法检测处理后大鼠肝脏中芦荟大黄素、大黄酸、大黄素、 Chrysophanol、厚朴酚、 Rheo Chrysophanol、厚朴碱、橙皮苷、柚皮素和柚皮苷的组织浓度。评估血清中的丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）、肝脏中的炎症介质以及病理评分。
在肝脏中检测到了DCQD的主要成分，其浓度呈剂量依赖性增加。高剂量的DCQD在改善病理损伤、降低肝脏中促炎介质肿瘤坏死因子-α和白细胞介素（IL）-6以及增加抗炎介质IL-4和IL-10方面显示出最大效果。MG组胰腺的病理评分显著高于SOG组（<0.05）。DCQD可降低SAP大鼠胰腺和肝脏的病理评分，尤其是HDG组。与SOG组相比，MG组血清中的ALT和AST水平较高（<0.05），而MG组和HDG组之间无统计学差异。
基于其成分在肝脏中的分布，DCQD可通过改变SAP大鼠的炎症反应来减轻肝脏损伤。
