左甲哌卡因通过 TRAF6/JNK 信号通路对 ConA 诱导的肝损伤起保护作用。
The Protective Effects of Levo-Tetrahydropalmatine on ConA-Induced Liver Injury Are via TRAF6/JNK Signaling.
机构信息
Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
Shanghai Tenth Hospital, School of Clinical Medicine of Nanjing Medical University, Shanghai 200072, China.
出版信息
Mediators Inflamm. 2018 Dec 4;2018:4032484. doi: 10.1155/2018/4032484. eCollection 2018.
AIMS
Levo-tetrahydropalmatine (L-THP) is an active ingredient of W. T. Wang, which has many bioactive properties. Herein, we investigated the protective effects of L-THP on concanavalin A- (ConA-) induced hepatitis in mice and explored its possible mechanisms of these effects.
MAIN METHODS
Balb/c mice were intravenously injected with 25 mg/kg ConA to generate a model of acute autoimmune hepatitis, and L-THP (20 or 40 mg/kg) was administered orally once daily for 5 d before the ConA injection. The liver enzyme levels, proinflammatory cytokine levels, and other marker protein levels were determined 2, 8, and 24 h after ConA injection.
RESULTS
L-THP could decrease serum liver enzymes and pathological damage by reducing the release of inflammatory factors like IL-6 and TNF-. The results of Western Blot and PCR indicated that L-THP could ameliorate liver cell apoptosis and autophagy. L-THP could suppress T lymphocyte proliferation and the production of TNF- and IL-6 induced by ConA in a dose-dependent manner . Additionally, the protective functions of L-THP depended on downregulating TRAF6/JNK signaling. The present study indicated that L-THP attenuated acute liver injury in ConA-induced autoimmune hepatitis by inhibiting apoptosis and autophagy via the TRAF6/JNK pathway.
目的
左旋延胡索乙素（L-THP）是王炜团队研究的一种具有多种生物活性的有效成分。本研究旨在探讨 L-THP 对刀豆蛋白 A（ConA）诱导的小鼠肝炎的保护作用及其可能的作用机制。
方法
Balb/c 小鼠尾静脉注射 25mg/kg ConA 建立急性自身免疫性肝炎模型，L-THP（20 或 40mg/kg）灌胃给药，连续 5d，于 ConA 注射后 2、8 和 24h 检测血清肝酶水平、促炎细胞因子水平及其他标志物蛋白水平。
结果
L-THP 通过降低 IL-6 和 TNF-α等炎症因子的释放，降低血清肝酶水平和病理损伤。Western blot 和 PCR 结果表明，L-THP 可减轻细胞凋亡和自噬。L-THP 可剂量依赖性抑制 ConA 诱导的 T 淋巴细胞增殖以及 TNF-α和 IL-6 的产生。此外，L-THP 的保护作用依赖于下调 TRAF6/JNK 信号通路。本研究表明，L-THP 通过 TRAF6/JNK 通路抑制细胞凋亡和自噬，减轻 ConA 诱导的急性肝损伤。
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