| 张露露,余真君,何宝泽.柚皮素对自身免疫性肝炎小鼠保护作用及TRAF6/JNK信号通路的影响[J].浙江中西医结合杂志,2021,31(9): |
| 柚皮素对自身免疫性肝炎小鼠保护作用及TRAF6/JNK信号通路的影响 |
| The protective effect of naringenin on mice with autoimmune hepatitis and its effect on TRAF6/JNK signaling pathway |
| 投稿时间：2021-01-08 修订日期：2021-06-11 |
| DOI： |
| 中文关键词: 柚皮素 自身免疫性肝炎 TRAF6/JNK信号通路 保护作用 |
| 英文关键词:Naringin Autoimmune hepatitis TRAF6/JNK signaling pathway Protective effect |
| 基金项目:浙江省医药卫生科技计划项目（2018KY914）；台州市科技计划项目（1801ky22） |
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| 中文摘要: |
| 目的：探讨柚皮素对自身免疫性肝炎(AIH)小鼠保护作用及肿瘤坏死因子受体相关因子6(TRAF6)/c-Jun氨基末端激酶(JNK)信号通路的影响。方法：将72只雄性C57BL/6小鼠随机分为阴性对照组、模型组、柚皮素低(30 mg/kg)、中(60 mg/kg)、高(120 mg/kg)剂量组和阳性对照组(2 mg/kg),每组12只。除阴性对照组外,其余各组小鼠一次性尾静脉注射刀豆球蛋白A(ConA)(12 mg/kg)制备AIH模型,阴性对照组尾静脉注射等量生理盐水。注射完毕之后,柚皮素低、中、高剂量组和阳性对照组分别灌胃相应药物,阴性对照组和模型组灌胃给予等量生理盐水,每天1次,持续给予5d。末次灌胃24 h后检测小鼠血清中丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)水平,苏木精-伊红(HE)染色观察小鼠肝组织病理学改变,酶联免疫吸附(ELISA)检测小鼠肝组织中白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平,蛋白免疫印迹法检测小鼠肝组织中TRAF6、JNK、磷酸化JNK(p-JNK)、B细胞淋巴瘤/白血病-2(Bcl-2)和Bcl-2相关X蛋白(Bax)水平。结果：阴性对照组小鼠肝脏结构未见明显异常；模型组小鼠见大量片肝细胞坏死区域,肝索排列紊乱,同时伴有炎性细胞浸润；柚皮素各剂量组和阳性对照组病理改变较模型组减轻,且柚皮素高剂量组与阳性对照组只存在轻度肝细胞坏死。与阴性对照组比较,模型组小鼠血清中ALT、AST、肝组织中IL-6、TNF-α、TRAF6、p-JNK和Bax蛋白水平增加,Bcl-2蛋白和Bcl-2/Bax水平降低(P＜0.05)；与模型组比较,柚皮素低、中、高剂量组和阳性对照组小鼠血清中ALT、AST、肝组织中IL-6、TNF-α、TRAF6、p-JNK和Bax蛋白水平降低,Bcl-2蛋白和Bcl-2/Bax水平增加,柚皮素各剂量组之间呈剂量效应关系(P＜0.05)；各组小鼠肝组织中JNK蛋白水平变化不显著(P＞0.05)；柚皮素高剂量组与阳性对照组作用相似(P＞0.05)。结论：柚皮素可能通过抑制TRAF6/JNK信号通路,减轻AIH小鼠肝脏炎症反应,对AIH小鼠肝脏具有保护作用。 |
| 英文摘要: |
| Objective: To investigate the effect of protective effect of naringenin on mice with autoimmune hepatitis(AIH) and its effect on tumor necrosis factor receptor-associated factorS6(TRAF6)/c-Jun N-terminal kinase(JNK) signaling pathway. Methods: 72 male C57BL/6 mice were randomly divided into negative control group, model group, naringenin low (30 mg/kg), medium (60 mg/kg), high (120 mg/kg) dose groups and positive control group (2 mg/kg), with 12 mice in each group. Except for the negative control group, the other groups were injected with concanavalin A (ConA) (12 mg/kg) via tail vein to prepare AIH model, while the negative control group was injected with equal amount of normal saline. After the injection, naringenin low, medium, high dose groups and positive control group were given corresponding drugs by gavage, while the negative control group and model group were given the same amount of normal saline, once a day for 5 days. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected 24 hours after the last gavage, hematoxylin eosin (HE) staining was used to observe the pathological changes of liver tissue in mice, the levels of interleukin-6 (IL-6) and tumor necrosis factor-α(TNF-α) in liver tissue of mice were detected by enzyme-linked immunosorbent assay (ELISA), the levels of TRAF6, JNK, phosphorylated JNK(p-JNK), B-cell lymphoma/leukemia-2(Bcl-2) and Bcl-2 related X protein(Bax) in liver tissue of mice were detected by Western blot. Results: The liver structure of the negative control group was not significantly abnormal; in the model group, a large number of necrotic areas of hepatocytes were seen, the arrangement of liver cords was disordered, and inflammatory cell infiltration was found; the pathological changes in the naringin each dose group and the positive control group were less than those in the model group, and only slight hepatocyte necrosis was found in the naringin high dose group and the positive control group. Compared with the negative control group, the serum ALT, AST, liver tissue IL-6, TNF-α, TRAF6, p-JNK and Bax protein levels of mice in the model group were increased, the Bcl-2 protein and Bcl-2/Bax levels decreased(P<0.05). Compared with the model group, the serum ALT, AST, liver tissue IL-6, TNF-α, TRAF6, p-JNK and Bax protein levels of mice in the low, middle, high dose naringin group and the positive control group were decreased, the Bcl-2 protein and Bcl-2/Bax levels increased, and there was a dose effect relationship between naringenin dose groups(P<0.05). The JNK protein level in the mice liver tissue of each group was not significantly changed (P>0.05). The effect in the naringin high-dose group was similar to that of positive control group (P>0.05). Conclusion: Naringenin may protect the liver of AIH mice by inhibiting TRAF6/JNK signaling pathway and reducing liver inflammation in AIH mice. |
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