黄精通过氧化应激和线粒体凋亡途径保护CCl4诱导的大鼠急性肝损伤

doi:10.5246/jcps.2021.04.025

中国药学(英文版) ›› 2021, Vol. 30 ›› Issue (4): 306-318.DOI: 10.5246/jcps.2021.04.025

黄精通过氧化应激和线粒体凋亡途径保护CCl4诱导的大鼠急性肝损伤

韩春杨^#, 孙桃桃^#, 范广太^#, 刘亚伟, 刘翠艳^*()

安徽农业大学动物科技学院, 安徽合肥 230036

收稿日期:2020-11-15 修回日期:2020-12-20 接受日期:2021-01-15 出版日期:2021-04-30 发布日期:2021-04-30
通讯作者: 刘翠艳
作者简介:
+ Tel.: +86-551-65786328, E-mail: cyliu@ahau.edu.cn
基金资助:
Natural Science Foundation of the Anhui Higher Education Institutions of China (Grant No. KJ2019A0166), and the National Natural Science Foundation of China (Grant No. 31772786).

Protective effects of Polygonatum sibiricum against CCl4-induced acute liver injury in rats through oxidative stress and mitochondrial apoptotic pathways

Chunyang Han^#, Taotao Sun^#, Guangtai Fan^#, Yawei Liu, Cuiyan Liu^*()

College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China

Received:2020-11-15 Revised:2020-12-20 Accepted:2021-01-15 Online:2021-04-30 Published:2021-04-30
Contact: Cuiyan Liu
About author:
# These authors contributed equally to this work.

摘要/Abstract

摘要：

研究黄精(Polygonatum sibiricum, PS)对CCl₄诱导的大鼠肝损伤的保护作用及其抗氧化机制。采用一次性腹腔注射50%四氯化碳油溶液建立大鼠急性肝损伤模型, 用黄精水提物(PSAE)灌胃治疗, 水飞蓟素作为阳性对照药物, 连续7天。PSAE显著降低了血清丙氨酸转氨酶、天冬氨酸转氨酶和碱性磷酸酶(AST、ALT和ALP)的水平(P < 0.05), 增加了肝组织谷胱甘肽(GSH)和超氧化物歧化酶(T-SOD)的水平(P < 0.05), 降低了肝组织中丙二醛的活性(P < 0.05), 并显著降低了肝细胞中的活性氧水平(P < 0.05)。在肝组织中, 核因子类红细胞2相关因子2(Nrf2), NAD(P)H醌脱氢酶1(NQO-1), 血红素加氧酶1(HO-1) mRNA的表达水平显著升高, p53 mRNA表达显著降低(P < 0.05), Bcl-2(P < 0.05)和Bcl-xL mRNA的表达升高, HO-1蛋白表达升高, Keap-1 mRNA表达无明显差异(P > 0.05)。因此, 黄精对CCl₄诱导的急性肝损伤有较好的保护作用, 其机制与有效调节Nrf2-Keap1-ARE通路相关基因和蛋白质的表达、抑制p53途径介导的肝细胞凋亡有关。

关键词: 黄精, CCl4, 大鼠, 急性肝损伤, 氧化应激, 细胞凋亡

Abstract:

In the present study, we aimed to investigate the hepatoprotective effect of Chinese herbal medicine Polygonatum sibiricum (PS). In this study, a rat acute liver injury (ALI) model was established by a single intraperitoneal injection of 50% CCl₄oil solution, and the rats were treated intragastrically with Polygonatum sibiricum aqueous extract (PSAE). The results showed that PSAE significantly decreased the serum levels of ALT, AST and ALP, increased the activities of glutathione (GSH) and superoxide dismutase (SOD), decreased malondialdehyde (MDA) activity in hepatic tissue, and decreased the reactive oxygen species (ROS) level in hepatocytes. The expressions of Nrf2, NQO-1, HO-1, Bcl-2, Bcl-xL mRNA, and HO-1 proteins were elevated, and the expression of p53 mRNA was decreased. In conclusion, PSAE exerted a powerful protective action against CCl₄-induced ALI in rats via effectively regulating the expressions of Nrf2-Keap1-ARE related genes and proteins, and inhibiting hepatocyte apoptosis. These outcomes provided evidence that PS had apparent hepatoprotective effect.

Key words: Polygonatum sibiricum, CCl4, Rat, Acute liver injury, Oxidative stress, Apoptosis

Supporting:

韩春杨, 孙桃桃, 范广太, 刘亚伟, 刘翠艳. 黄精通过氧化应激和线粒体凋亡途径保护CCl4诱导的大鼠急性肝损伤[J]. 中国药学(英文版), 2021, 30(4): 306-318.

Chunyang Han, Taotao Sun, Guangtai Fan, Yawei Liu, Cuiyan Liu. Protective effects of Polygonatum sibiricum against CCl4-induced acute liver injury in rats through oxidative stress and mitochondrial apoptotic pathways[J]. Journal of Chinese Pharmaceutical Sciences, 2021, 30(4): 306-318.

图/表 7

Figure 1. Effect of PSAE on liver coefficient of rats with liver injury induced by CCl4. n = 10 per group. *P < 0.05 vs. control; #P < 0.05 vs. model.

Figure 2. Effect of PSAE on liver general pathological changes with rat liver injury induced by CCl4. n = 10 per group.

Figure 3. Levels of MDA, GSH, SOD, CAT, ALP, ALT and AST in each group. (A) MDA level; (B) GSH level; (C) SOD level; (D) CAT Level; (E) ALP level; (F) ALT level; (G) AST level. n = 10 per group. *P < 0.05 vs. control; #P < 0.05 vs. model.

Figure 4. Level of ROS of hepatocytes in each group. (A) ROS level in the control group; (B) ROS level in the model group; (C) ROS level in the PSAE group; (D) ROS level in the PC group; (E) ROS level of hepatocytes in each group. n = 10 per group. *P < 0.05 vs. control; #P < 0.05 vs. model.

Figure 5. Levels of Nrf2, Keap-1, HO-1, NQO-1, p53, Bcl-2 and Bcl-xL mRNA in hepatic tissues in each group. (A) Level of Nrf2 mRNA; (B) Level of Keap-1 mRNA; (C) Level of HO-1 mRNA; (D) Level of NQO-1 mRNA; (E) Level of p53 mRNA; (F) Level of Bcl-2 mRNA; (G) Level of Bcl-xL mRNA. n = 10 per group. *P < 0.05 vs. control; #P < 0.05 vs. model.

Figure 6. Liver pathological changes in each group. (A) Control group; (B) Model group; (C) PSAE group; (D) PC group. n = 10 per group. Magnification, × 400. Those labeled S is the normal hepatic tissue, S1 is cell degeneration and vacuolization, S2 is the infiltration of inflammatory cells, S3 is congestion, and S4 is granular degeneration.

Figure 7. Expression of HO-1 protein in hepatic tissues in each group. n = 10 per group.

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黄精通过氧化应激和线粒体凋亡途径保护CCl4诱导的大鼠急性肝损伤

Protective effects of Polygonatum sibiricum against CCl4-induced acute liver injury in rats through oxidative stress and mitochondrial apoptotic pathways

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