Lee Tzung-Yan, Chang Hen-Hong, Wu Mei-Yao, Lin Han-Chieh
Graduate Institute of Traditional Chinese Medicine, Chang Gung University, Taoyuan, Taiwan.
J Pharm Pharmacol. 2007 Apr;59(4):583-90. doi: 10.1211/jpp.59.4.0014.
The accumulation of hydrophobic bile acids in the liver is considered to play a pivotal role in the induction of apoptosis of hepatocytes during cholestasis. Thus, factors that affect apoptosis may be used to modulate liver fibrosis. Yin-Chen-Hao-Tang (YCHT) decoctions have been recognised as a hepatoprotective agent for jaundice and various types of liver diseases. We used an experimental rat model of bile-duct ligation (BDL) to test whether YCHT plays a regulatory role in the pathogenesis of hepatic apoptosis. BDL-plus-YCHT groups received 250 or 500 mg kg (-1) YCHT by gavage once daily for 27 days. YCHT significantly ameliorated the portal hypertensive state and serum TNF-alpha compared with the vehicle-treated control group. In BDL-plus-YCHT-treated rats, hepatic glutathione contents were significantly higher than than in BDL-only rats. BDL caused a prominent liver apoptosis that was supported by an increase in Bax and cytochrome c protein and increased expression of Bax and Bcl-2 messenger RNA. The normalising effect of YCHT on expression of Bax and Bcl-2 mRNA was dependent on the dose of YCHT, 500 mg kg (-1) having the greater effect on both Bax and Bcl-2 of mRNA levels. Additionally, YCHT treatment down-regulated both hepatic caspase-3 and -8 activities of BDL rats. This study demonstrates the anti-apoptotic properties of YCHT and suggests a potential application of YCHT in the clinical management of hepatic disease resulting from biliary obstruction.
胆汁淤积期间,肝脏中疏水性胆汁酸的蓄积被认为在诱导肝细胞凋亡中起关键作用。因此,影响细胞凋亡的因素可能被用于调节肝纤维化。茵陈蒿汤已被公认为治疗黄疸及各类肝病的保肝药物。我们使用胆管结扎(BDL)实验大鼠模型来测试茵陈蒿汤是否在肝脏细胞凋亡的发病机制中发挥调节作用。BDL加茵陈蒿汤组大鼠每天经口灌胃给予250或500 mg·kg⁻¹茵陈蒿汤,持续27天。与赋形剂处理的对照组相比,茵陈蒿汤显著改善了门静脉高压状态和血清肿瘤坏死因子-α水平。在BDL加茵陈蒿汤处理的大鼠中肝脏谷胱甘肽含量显著高于仅行BDL的大鼠。BDL导致明显的肝脏细胞凋亡,这表现为Bax和细胞色素c蛋白增加以及Bax和Bcl-2信使核糖核酸表达增加。茵陈蒿汤对Bax和Bcl-2 mRNA表达的正常化作用取决于茵陈蒿汤的剂量,500 mg·kg⁻¹对Bax和Bcl-2的mRNA水平影响更大。此外,茵陈蒿汤处理下调了BDL大鼠肝脏中半胱天冬酶-3和-8的活性。本研究证明了茵陈蒿汤的抗凋亡特性,并提示茵陈蒿汤在临床管理胆汁淤积所致肝病方面具有潜在应用价值。