Specnuezhenide reduces carbon tetrachloride-induced liver injury in mice through inhibition of oxidative stress and hepatocyte apoptosis
Specnuezhenide reduces carbon tetrachloride-induced liver injury in mice through inhibition of oxidative stress and hepatocyte apoptosis
复制标题
特女贞胺通过抑制氧化应激和肝细胞凋亡来减轻四氯化碳引起的小鼠肝损伤
DOI：
10.1093/jpp/rgab164
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发表时间：
2021-12-19
影响因子：
3.3
通讯作者：
Wang, Jingwen
中科院分区：
文献类型：
--
作者：
Hu, Dongmei;Huang, Shaojie;Wang, Jingwen
目的探讨特诺真尼对四氯化碳（CCl4）致小鼠肝损伤的保护作用。方法雄性C57BL/6小鼠在口服specnuezhenide 7 d后，腹腔注射CCl4（0.5%花生油稀释）10 ml/kg体重治疗急性肝损伤。最后一次注射CCl4 24小时后，对小鼠实施安乐死，并收集血浆和肝脏样本。结果表明，specnuezhenide能显著且剂量依赖性地降低血清丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）活性和相对肝脏重量，改善CCl4所致的组织病理损伤，降低丙二醛（MDA）水平，提高抗氧化酶、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-Px）活性。此外，specnuezhenide促进核因子红系2相关因子2 （Nrf2）的表达和核易位，提高Nrf2信号相关基因血红素加氧酶-1 （HO-1）、谷氨酸-半胱氨酸连接酶催化亚基（GCLC）和NAD(P)H：醌氧化还原酶1 （NQO1）的mRNA和蛋白表达。最后，TUNEL染色和免疫组织化学表明，specnuezhenide通过上调b细胞淋巴瘤2 （Bcl-2）表达和下调Bcl-2相关X （Bax）表达来阻止ccl4诱导的肝细胞凋亡。结论Specnuezhenide通过激活Nrf2信号通路抑制氧化应激，减少肝细胞凋亡，从而减轻ccl4诱导的小鼠肝损伤。
Objectives This study aimed to investigate the hepatoprotective effects of specnuezhenide against carbon tetrachloride (CCl4)-induced liver injury in mice. Methods Male C57BL/6 mice were intraperitoneally injected with 10 ml/kg body weight of CCl4 (0.5% diluted in arachis oil) for acute liver injury after oral administration of specnuezhenide for 7 days. Twenty-four hours after the final CCl4 injection, mice were euthanized and plasma and liver samples were collected. Key findings The results showed that specnuezhenide markedly and dose-dependently reduced serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) activity and relative liver weight, as well as ameliorated histopathological damage caused by CCl4 and decreased malondialdehyde (MDA) levels, and increased the activity of antioxidant enzymes, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Moreover, specnuezhenide promoted the expression and nuclear translocation of the nuclear factor erythroid 2-related factor 2 (Nrf2) and increased the mRNA and protein expression of Nrf2 signalling-related genes heme oxygenase-1 (HO-1), glutamate-cysteine ligase catalytic subunit (GCLC) and NAD(P)H:quinone oxidoreductase 1 (NQO1). Finally, TUNEL staining and immunohistochemistry indicated that specnuezhenide prevented CCl4-induced hepatocytic apoptosis by up-regulating B-cell lymphoma 2 (Bcl-2) expression and downregulating Bcl-2-associated X (Bax) expression. Conclusions Specnuezhenide reduced CCl4-induced liver injury in mice by inhibiting oxidative stress via activation of Nrf2 signalling and decreasing hepatocyte apoptosis.