天然产物研究与开发 ›› 2018, Vol. 30 ›› Issue (2): 212-217.doi: 10.16333/j.1001-6880.2018.2.007

所属专题: No.2

• 研究论文 • 上一篇    下一篇

过墙风总黄酮对四氯化碳致急性肝损伤小鼠的保护作用及机制研究

黄思茂1,高雅1,曹后康1,葸博婷1,王刚1,马冬梅1,张可锋1,2*   

  1. 1桂林医学院药学院,桂林 541004;2甘肃中医药大学药学院,兰州 730000
  • 出版日期:2018-02-28 发布日期:2018-02-28
  • 基金资助:

    广西八桂学者专项(2017-143)

Protective Effects and Functional Mechanism of Clerodendrum philippinum Schauer var. simplex Mlodenke Total Flavonoids on Acute Liver Injury Induced by Carbon Tetrachloride in Mice

HUANG Si-mao1, GAO Ya1, CAO Hou-kang1, XI Bo-ting1, WANG Gang1, MA Dong-mei1, ZHANG Ke-feng1,2*   

  1. 1College of Pharmacy, Guilin Medical University, Guilin 541004, China; 2College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou 730000, China
  • Online:2018-02-28 Published:2018-02-28

摘要: 探讨过墙风总黄酮(CPTF)对四氯化碳(CCl4)致急性肝损伤小鼠的保护作用及作用机制。将60只小鼠随机分为正常组、模型组、水飞蓟素组(150 mg/kg)、CPTF高、中、低剂量组(200、100、50 mg/kg),每组10只。各给药组每天灌胃对应剂量的药物(25 mL/kg),正常组与模型组每天灌胃等体积蒸馏水,连续灌胃10 d。末次给药2 h后,除正常组腹腔注射花生油外,其余各组均腹腔注射0.1%的CCl4花生油溶液(10 mL/kg)。禁食不禁水16 h后,眼球取血,处死后收集肝脏。生化法检测血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)、总超氧化物歧化酶(T-SOD)、丙二醛(MDA)和谷胱甘肽过氧化物酶(GSH-Px)的含量,酶联免疫吸附试验(ELISA)检测肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)和白介素-6(IL-6)在肝组织中的含量。蛋白免疫印迹实验(Western blot)检测肝组织中酪氨酸蛋白激酶2(JAK2)、磷酸化JAK2(p-JAK2)、信号转导和转录激活因子3(STAT3)和磷酸化STAT3(p-STAT3)含量,HE染色观察肝组织病理学变化。结果显示,与模型组比较,CPTF可显著改善肝组织病变,降低血清中AST、ALT和MDA含量(P< 0.05),提高T-SOD和GSH-PX活性(P< 0.05),下调肝组织中TNF-α、IL-1β和IL-6表达(P< 0.05),并抑制p-JAK2和p-STAT3水平(P< 0.05)。综上所述,CPTF对CCl4致急性肝损伤小鼠具有保护作用,可减轻肝组织损伤程度,其作用机制可能与抗氧化、抑制炎症反应,并调控JAK2/STAT3信号通路有关。

关键词: 过墙风, 总黄酮, 四氯化碳, 急性肝损伤, 氧化应激, 炎症反应, JAK2/STAT3信号通路

Abstract: To explore the protective effects and its mechanism of Clerodendrum philippinum Schauer var. simplex Mlodenke total flavonoids (CPTF) on acute liver injury induced by carbon tetrachloride (CCl4) in mice.60 mice were randomly divided into normal group,model group,silymarin group (150 mg/kg),CPTF-high,medium and low dose group (200,100,50 mg/kg).The normal group and model group were given equivoluminal distilled water,and other groups were given the corresponding dose of drugs (25 mL/kg) for 10 days.After 2 h of the last administration,the mice of all groups except the normal group were injected intraperitoneally with 0.1% CCl4 peanut oil solution (10 mL/kg).16 h later,the blood was taken by removing eye balls,and the liver tissue was collected after killing the mice.The serum contents of alanine aminotransferase (ALT),aspartate aminotransferase (AST),total superoxide dismutase (T-SOD),malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) were measured by biochemical method;the levels of tumor necrosis factor-α (TNF-α),interleukin-1β (IL-1β) and interleukin-6 (IL-6) in liver tissue were detected by enzyme-linked immunosorbent assay (ELISA);janus kinase 2 (JAK2),phosphorylated JAK2 (p-JAK2),signal transducer and activator of transcription 3 (STAT3) and phosphorylated STAT3 (p-STAT3) in liver tissue were detected by Western blot;the histopathological changes of liver were observed by HE staining.The results showed that CPTF could significantly improve the liver tissue lesion,decrease the levels of AST,ALT and MDA in serum (P< 0.05),enhance the activity of T-SOD and GSH-Px (P < 0.05),inhibit the hepatic levels of TNF-α,IL-1β and IL-6 (P< 0.05),and inhibit the expression of p-JAK2 and p-STAT3 (P < 0.05).In summary,CPTF had a protective effect on CCl4-induced acute liver injury in mice,which could reduce the degree of liver injury,and its mechanism may be related to anti-oxidation,inhibition of inflammation and regulation of JAK2/STAT3 signaling pathway.

Key words: Clerodendrum philippinum Schauer var.simplex Mlodenke, total flavonoids, carbon tetrachloride, acute liver injury, oxidative stress, inflammatory response, JAK2/STAT3 signaling pathway

中图分类号: 

Q939.9