Guo Shun, Zhang Song, Liu Linna, Yang Peng, Dang Xueliang, Wei Huamei, Hu Na, Shi Lei, Zhang Yan
Department of Pharmacy, Tangdu Hospital, Fourth Military Medical University.
Biol Pharm Bull. 2018 Jun 1;41(6):869-876. doi: 10.1248/bpb.b17-00972. Epub 2018 Apr 4.
Pinelliae Rhizoma Praeparatum (PRP) as traditional Chinese medicine had been used for hepatic diseases in combinative forms. However, the effect of PRP was not clear when used alone. So to explore the hepatoprotective/hepatotoxin of PRP is necessary. The activities of PRP were investigated in acetaminophen-induced hepatic injury mice. Liver function markers, hepatic oxidative stress markers were evaluated. Bile acids metabolic transports and nuclear factor erythroid 2-related factor 2 (Nrf2) were detected. As a drug for the treatment of liver diseases, PRP slightly restored the parameters towards normal in model mice only in low dosage, and also had no antioxidant activity and regulate Nrf2. Cholestasis was significantly elevated in model mice when pretreatment with routine or high dosage of PRP, but had no effect on normal mice. Bile salt export pump (Bsep) and multidrug resistance-associated protein 2 (Mrp2) in model mice were markedly increased when pretreatment with low dose PRP, but significantly decreased when pretreatment in routine or high dosage. Mrp3 was significantly induced in model mice after pretreatment of PRP. But the adjustment effect to bile acids transporters by PRP was not significant in normal mice. These results reveal that PRP has the different effects on bile acids transporter in hepatic injury mice, and therefore, the dosage of PRP need to be paid attention to when it is used in clinical hepatic injury.
法半夏作为传统中药，已被用于多种肝病的联合治疗。然而，单独使用法半夏时其疗效尚不清楚。因此，有必要探究法半夏的保肝/肝毒性作用。本研究在对乙酰氨基酚诱导的肝损伤小鼠中研究了法半夏的作用。评估了肝功能标志物、肝脏氧化应激标志物。检测了胆汁酸代谢转运体和核因子E2相关因子2（Nrf2）。作为一种治疗肝病的药物，法半夏仅在低剂量时能使模型小鼠的参数略有恢复正常，且无抗氧化活性和调节Nrf2的作用。用常规剂量或高剂量法半夏预处理时，模型小鼠的胆汁淤积显著升高，但对正常小鼠无影响。低剂量法半夏预处理时，模型小鼠的胆盐输出泵（Bsep）和多药耐药相关蛋白2（Mrp2）显著增加，但常规剂量或高剂量预处理时则显著降低。法半夏预处理后，模型小鼠的Mrp3显著诱导。但法半夏对正常小鼠胆汁酸转运体的调节作用不显著。这些结果表明，法半夏对肝损伤小鼠的胆汁酸转运体有不同影响，因此，临床应用法半夏治疗肝损伤时需注意其剂量。
