Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Guangdong Yifang Pharmaceutical Co., Ltd, Foshan, 528244, China.
J Ethnopharmacol. 2020 Apr 24;252:112602. doi: 10.1016/j.jep.2020.112602. Epub 2020 Jan 28.
Hyperthyroidism is closely associated with liver injury. The preliminary clinical observation suggests that Yinning Tablet, a hospitalized preparation of traditional Chinese formula for hyperthyroidism, improves not only hyperthyroidism, but also hyperthyroidism-associated liver injury.
To evaluate the effect and underlying mechanisms of Yinning Tablet on thyroid hormone-induced liver injury.
Female rats were orally administered L-thyroxine (1 mg/kg) once daily for 60 days, and co-treated with the carefully identified Yinning Tablet extract (0.6-2.4 g/kg) during the last 30 days. Blood and liver variables were determined enzymatically, histologically, by ELISA, radioimmunoassay, Real-Time PCR or Western blot, respectively.
Co-treatment with the extract attenuated L-thyroxine-induced increases in serum alanine transaminase and aspartate transaminase activities, the ratio of liver weight to body weight, cytoplasmic vacuolization in hepatocytes, infiltrated inflammatory cells and confused structures in liver tissue, accompanied by attenuation of increased serum triiodo-l-thyronine concentration and hepatic deiodinase type I overexpression in rats. Importantly, Yinning Tablet suppressed L-thyroxine-triggered hepatic Bax, cleaved caspases-3, -8 and -9 protein overexpression, and Bcl-2 protein downregulation. Furthermore, the increases in cytochrome c protein expression, Ca-ATPase activity and malondialdehyde content, and decreases in activities of Na/K-ATPase, catalase, superoxide dismutase and glutathione peroxidase, and total antioxidant capacity in liver tissue were attenuated.
The present results suggest that Yinning Tablet ameliorates thyroid hormone-induced liver injury in rats by regulating mitochondria-mediated apoptotic signals. Our findings go insight into the pharmacological basis of the hospitalized preparation for treatment of hyperthyroidism-associated liver injury.
甲状腺功能亢进症与肝损伤密切相关。初步临床观察表明，银宁片是一种治疗甲状腺功能亢进症的中药院内制剂，不仅能改善甲状腺功能亢进症，还能改善甲状腺功能亢进症相关的肝损伤。
评价银宁片对甲状腺激素诱导的肝损伤的作用及机制。
雌性大鼠每天口服给予 L-甲状腺素（1mg/kg）一次，连续 60 天，在最后 30 天同时给予精心鉴定的银宁片提取物（0.6-2.4g/kg）。通过酶法、组织学、ELISA、放射免疫测定、实时 PCR 或 Western blot 分别测定血液和肝脏变量。
提取物与 L-甲状腺素共同处理可减轻 L-甲状腺素引起的血清丙氨酸氨基转移酶和天冬氨酸氨基转移酶活性、肝重/体重比、肝细胞细胞质空泡化、浸润性炎症细胞和肝组织结构紊乱的增加，同时伴有血清三碘甲状腺原氨酸浓度的升高和肝脱碘酶 I 型表达的上调。重要的是，银宁片抑制了 L-甲状腺素触发的肝 Bax、裂解的 caspase-3、-8 和-9 蛋白过表达，以及 Bcl-2 蛋白下调。此外，还抑制了肝组织中线粒体钙 ATP 酶活性和丙二醛含量的增加、Na/K-ATP 酶、过氧化氢酶、超氧化物歧化酶和谷胱甘肽过氧化物酶活性及总抗氧化能力的降低。
本研究结果表明，银宁片通过调节线粒体介导的凋亡信号改善甲状腺激素诱导的大鼠肝损伤。我们的研究结果深入了解了治疗甲状腺功能亢进症相关肝损伤的院内制剂的药理学基础。
