七叶树（Venoplant®）对刀豆蛋白 A 诱导的肝损伤的保护作用。

The Protective Effect of Aesculus hippocastanum (Venoplant®) Against Concanavalin A-Induced Liver Injury.

机构信息

Department of Pharmacy, Gan Su Province Hospital, Lan Zhou, China.

Department of Pharmacy, Gan Su Province Hospital, Lan Zhou, China,

出版信息

Pharmacology. 2019;104(3-4):196-206. doi: 10.1159/000501258. Epub 2019 Jul 23.

DOI:10.1159/000501258

PMID:31336368

Abstract

AIM

The present study was performed to investigate the effect of Aesculus hippocastanum (AH; Venoplant®) on concanavalin A (ConA)-induced acute liver injury and explore the mechanism in mice.

METHODS

ConA (20 mg/kg) was administered via tail vein injection to induce hepatic damage. The groups of AH (Venoplant®) were given at 65.8, 131.6, and 263.2 mg/kg by oral gavages for 20 days. The serum levels of aspartate transaminase (AST), alanine aminotransferase (ALT), total protein (TP), and albumin (Alb) were determined by automatic biochemical analyzer, and the Alb/globulin (A/G) ratio was calculated. Tumor necrosis factor-α (TNF-α) and IFN-γ levels were assayed by enzyme-linked immunosorbent assay. The liver tissue was attained by hematoxylin and eosin, and the histopathological changes were calculated. The cell apoptosis was assayed by terminal dUTP nick-end labeling. The malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) content of liver tissue were assayed by related kits. The activity of caspase-3 was detected by spectrophotometry. The expressions of cytochrome c, Bax, Bcl-2, c-Jun N-terminal kinase (JNK), and p-JNK were detected by western blot.

RESULTS

The results showed that the levels of ALT, AST, IFN-γ, and TNF-α in AH (Venoplant®) groups were significantly lower than those in ConA-injured group, while the levels of TP, Alb, and A/G were significantly higher. The SOD and GSH levels were significantly increased, and the MDA level was decreased; liver histopathology was changed consistently with the serological indicators, AH (Venoplant®) treatment significantly reduced the pathological damage and cell apoptosis; while in AH (Venoplant®) group, the expressions of cytochrome c, caspase-3, Bax/Bcl-2 ratio, and p-JNK were significantly decreased.

CONCLUSION

AH (Venoplant®) could significantly protect the ConA-induced acute liver injury in mice via inhibition of reactive oxygen species and JNK pathway.

摘要

目的

本研究旨在探讨欧洲七叶树（AH；Venoplant®）对刀豆蛋白 A（ConA）诱导的急性肝损伤的影响，并探讨其在小鼠中的作用机制。

方法

通过尾静脉注射 ConA（20mg/kg）诱导肝损伤。AH（Venoplant®）组分别给予 65.8、131.6 和 263.2mg/kg 灌胃 20 天。采用自动生化分析仪检测血清天门冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）、总蛋白（TP）和白蛋白（Alb）水平，并计算 Alb/球蛋白（A/G）比值。采用酶联免疫吸附试验检测肿瘤坏死因子-α（TNF-α）和干扰素-γ（IFN-γ）水平。采用苏木精-伊红染色法获取肝组织，计算肝组织病理变化。采用末端脱氧核苷酸转移酶介导的缺口末端标记法检测细胞凋亡。采用相关试剂盒检测肝组织丙二醛（MDA）、超氧化物歧化酶（SOD）和谷胱甘肽（GSH）含量。采用分光光度法检测 caspase-3 活性。采用 Western blot 检测细胞色素 c、Bax、Bcl-2、c-Jun N-末端激酶（JNK）和磷酸化 JNK（p-JNK）的表达。

结果

结果表明，AH（Venoplant®）组 ALT、AST、IFN-γ和 TNF-α水平明显低于 ConA 损伤组，TP、Alb 和 A/G 水平明显升高。SOD 和 GSH 水平显著升高，MDA 水平降低；肝组织病理学变化与血清学指标一致，AH（Venoplant®）治疗显著减轻了病理损伤和细胞凋亡；同时，在 AH（Venoplant®）组，细胞色素 c、caspase-3、Bax/Bcl-2 比值和 p-JNK 的表达明显降低。