Yinning Tablet, a hospitalized preparation of Chinese herbal formula for hyperthyroidism, ameliorates thyroid hormone-induced liver injury in rats: Regulation of mitochondria-mediated apoptotic signals.
Yinning Tablet, a hospitalized preparation of Chinese herbal formula for hyperthyroidism, ameliorates thyroid hormone-induced liver injury in rats: Regulation of mitochondria-mediated apoptotic signals.
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DOI：
10.1016/j.jep.2020.112602
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发表时间：
2020-01
影响因子：
5.4
通讯作者：
Qin Yang;Wenqin Liu;Dongmei Sun;Chunxia Wang;Yang-xue Li;Xiaoli Bi;Peng Gu;Haixing Feng;Fuling Wu;L. Hou;C. Hou;Yuhao Li
中科院分区：
文献类型：
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作者：
Qin Yang;Wenqin Liu;Dongmei Sun;Chunxia Wang;Yang-xue Li;Xiaoli Bi;Peng Gu;Haixing Feng;Fuling Wu;L. Hou;C. Hou;Yuhao Li
民族药理学相关性甲状腺机能亢进与肝损伤密切相关。初步临床观察表明，甲状腺机能亢进的住院制剂银宁片不仅能改善甲状腺机能亢进，还能改善甲状腺机能亢进相关性肝损伤。目的探讨银宁片对甲状腺激素性肝损伤的影响及其机制。材料与方法雌性大鼠口服l -甲状腺素（1 mg/kg），每天1次，连续60 d，最后30 d与精心鉴定的银宁片提取物（0.6 ~ 2.4 g/kg）共处理。血液和肝脏变量分别通过酶学、组织学、ELISA、放射免疫测定、实时荧光定量PCR或Western blot测定。结果枸杞子提取物可减轻l-甲状腺素引起的大鼠血清丙氨酸转氨酶和天冬氨酸转氨酶活性升高、肝重/体重比升高、肝细胞胞浆空泡化、炎症细胞浸润和肝组织结构混乱，同时降低血清三碘-l-甲状腺氨酸浓度升高和肝去碘酶I型过表达。重要的是，银宁片抑制l-甲状腺素引发的肝Bax，裂解caspase -3， -8和-9蛋白的过表达，以及Bcl-2蛋白的下调。肝组织细胞色素蛋白表达、Ca2+- atp酶活性和丙二醛含量升高，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降低，总抗氧化能力降低。结论银宁片可能通过调节线粒体介导的细胞凋亡信号改善甲状腺激素所致大鼠肝损伤。我们的研究结果深入了解了甲亢相关肝损伤住院治疗的药理学基础。
Ethnopharmacological relevanceHyperthyroidism 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.AimTo evaluate the effect and underlying mechanisms of Yinning Tablet on thyroid hormone-induced liver injury.Materials and methodsFemale 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.ResultsCo-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 cytochromecprotein expression, Ca2+-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.ConclusionThe 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.