胡萝卜苷对刀豆蛋白A诱导的急性肝损伤的保护作用

Protective Effect of Daucosterol on Acute Liver Injury Induced by Concanavalin A

关键词:  胡萝卜苷  刀豆蛋白A  自身免疫性肝炎  炎症  肝损伤

Key words:  daucosterol  concanavalin A  autoimmune hepatitis  inflammation  liver injury

摘要:

目的 探究胡萝卜苷对刀豆蛋白A （concanavalin A，conA）诱导的急性肝损伤的保护作用及相关机制。方法 将50只C57 BL/6小鼠随机分成5组：正常组、模型组和胡萝卜苷低、中、高剂量组，每组10只。尾静脉注射conA制备急性肝损伤模型后，胡萝卜苷各剂量组立即灌胃胡萝卜苷治疗，12 h后处死动物。测定肝指数，检测血清中谷丙转氨酶（alanine aminotransferase，ALT）、谷草转氨酶（aspartate aminotransferase，AST）活性及肿瘤坏死因子-a （tumor necrosis factor-α，TNF-α）、白细胞介素-1β（interleukin-1β，IL-1β）、白细胞介素-6（interleukin-6，IL-6）的含量。HE染色观察肝组织病理学改变。qRT-PCR检测TNF-α、IL-1β、IL-6在肝组织中的转录水平。Western blotting检测信号转导与转录激活子（signal transduction and activator of transcription，STAT3）及p-STAT3的表达。结果 胡萝卜苷各剂量组的血清ALT、AST、TNF-α、IL-1β、IL-6含量，肝脏TNF-α、IL-1β、IL-6 mRNA表达，肝脏STAT3、p-STAT3水平皆低于模型组（P<0.05或P<0.01）。HE染色结果也表明，胡萝卜苷的治疗能够有效减轻肝损伤。结论 胡萝卜苷具有抵抗conA诱导的肝损伤的作用，该作用可能与抑制STAT3的表达有关。

Abstract:

OBJECTIVE To explore the protective effect and mechanisms of daucosterol on acute liver injury induced by concanavalin A(conA). METHODS Fifty C57 BL/6 mice were randomly divided into 5 groups:normal group, model group, low, medium and high dose group of daucosterol, 10 rats in each group. After injection of conA into the tail vein, the daucosterol was administered immediately in each group of daucosterol. After 12 h, killed the animals. The liver index was measured, and the activity of alanine aminotransferase(ALT), aspartate aminotransferase(AST) and the contents of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β) and interleukin-6(IL-6) in serum were detected. The pathological changes of liver tissue were observed by HE. qRT-PCR was used to detect the transcription levels of TNF-α, IL-1β and IL-6 in liver. Western blotting was used to detect the expression of STAT3 and p-STAT3. RESULTS The indexes of each group of daucosterol were lower than the model group(P<0.05 or P<0.01), such as the content of ALT, AST, TNF-α, IL-1β, IL-6 in serum, the expression of TNF-α, IL-1β, IL-6 mRNA in liver, and the levels of STAT3 and p-STAT3 in liver. The results of HE staining also showed that the treatment of daucosterol can effectively reduce liver damage. CONCLUSION Daucosterol has a protective effect on liver injury induced by conA, which may be related to inhibition of STAT3 expression and activation.