黄连素对四氯化碳诱导的小鼠急性肝损伤的保护作用

Berberine Protect Mice Againest CCl4-induced Acute Liver Injury

关键词:  黄连素  四氯化碳  急性肝损伤  炎症  JAK2/STAT3

Key words:  berberine  CCl₄  acute liver injury  inflammation  JAK2/STAT3

摘要:

目的 探讨黄连素对四氯化碳(CCl₄)诱导的小鼠急性肝损伤的保护作用及其机制。方法 30只C57小鼠，♂，随机分为对照组、CCl₄组和黄连素组，每组10只。黄连素组在CCl₄注射前1 h腹腔注射黄连素(10 mg·kg^-1)，CCl₄组和黄连素组腹腔注射CCl₄橄榄油溶液(0.5%，5 mL·kg^-1)，对照组腹腔注射橄榄油溶液(0.5%，5 mL·kg^-1)。24 h后麻醉下处死小鼠，收集血清和肝脏标本，采用生化检测ALT和AST，HE染色后观察肝脏病理学形态，western blot检测JAK2和STAT3，p-JAK2和p-STAT3。RT-PCR和ELISA检测炎症因子白介素-6(IL-6)和白介素8(IL-8)和肿瘤坏死因子-α(TNF-α)的表达和分泌。结果 与对照组相比，CCl₄组病理改变明显增加，p-JAK2、p-STAT3蛋白表达量明显增加，JAK2和STAT3表达无明显变化，IL-6、IL-8和TNF-α表达和分泌明显增加。与CCl₄组相比，黄连素组病理改变明显减轻，p-JAK2、p-STAT3表达明显减少，IL-6、IL-8和TNF-α表达和分泌也明显减少，但JAK2和STAT3表达仍无明显变化。结论 黄连素预处理可通过抑制JAK2/STAT3信号通路激活而减少炎症反应，从而减轻CCl₄诱导的急性肝损伤。

Abstract:

OBJECTIVE To investigate potential protection and mechanism of berberine in CCl₄-induced acute liver injury. METHODS 30 male C57 mice were randomly divided into three groups: control group, CCl₄ group and berberine group. The mice in berberine group were injected berberine(10 mg·kg^-1, ip) before 1 h of CCl₄ injection. Moreover, the mice in berberine group and CCl4 group received CCl₄ olive oil injection(0.5%, 5 mL·kg^-1, ip), and the control group injected with olive oil(0.5%, 5 mL·kg^-1, ip). These mice were sacrificed after 24 h CCl₄ olive oil injection under anesthesia. Blood samples and liver tissue were collected. The liver dysfunction were evaluated by examining ALT and AST. The pathology of liver tissues was observed according to HE staining. and the protein level of JAK2, STAT3, p-JAK2 and p-STAT3 were measured by Western blotting. Moreover, the expression of IL-6, IL-8 and TNF-a were evaluated by RT-PCR and ELISA. RESULTS Compared with the control group, the liver dysfunction, the pathology change of liver tissue, the protein expression level of p-JAK2 and p-STAT3, and the expression of IL-6, IL-8 and TNF-α in CCl₄ group were significantly increased. while the protein expression level of JAK2 and STAT3 had no difference. compared with the CCl₄ group, the liver dysfunction, the pathology change of liver tissue, the protein expression level of p-JAK2 and p-STAT3 and the expression of IL-6, IL-8 and TNF-α in berberine group were significantly decreased, but the protein expression level of JAK2 and STAT3 still had no difference. CONCLUSION Berberin pretreatment protect mice against CCl₄-induced acute liver injury by suppressing inflammation though reducing the activation of JAK2/STATA3 signal pathway.