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黄连素对四氯化碳诱导的小鼠肝损伤的治疗作用研究

Research on therapeutic effect of berberine on carbon tetrachloride-induced liver injury in mice

  • 摘要: 为了探究黄连素对四氯化碳(CCl4)诱导的肝损伤的治疗效果及作用机制,试验选取80只健康昆明雌性小鼠,其中40只用于急性肝损伤试验,另外40只用于慢性肝损伤试验。急、慢性肝损伤试验中均将小鼠均随机分为对照组、模型组、黄连素组、水飞蓟宾组,每组10只。急性肝损伤试验中,黄连素组、水飞蓟宾组每天分别以黄连素(按体重25 mg/kg)溶液、水飞蓟宾(50 mg/kg)溶液预处理小鼠7 d后,一次性口服0.6%CCl4(按体重5μL/g)。慢性肝损伤试验中,采用灌胃0.6%CCl4溶液(按体重5μL/g),每周2次,连用6周,成功复制慢性肝损伤模型后黄连素组、水飞蓟宾组每天用黄连素(按体重50 mg/kg)溶液、水飞蓟宾(50 mg/kg)溶液治疗30 d。急性肝损伤和慢性肝损伤小鼠末次给药后间隔24 h,眼眶采血后处死小鼠,收集血清,检测天门冬氨酸氨基转移(AST)与丙氨酸氨基转移酶(ALT)活性;取肝脏称湿重,计算肝脏指数;取肝脏左叶约1 cm×1 cm×0.25 cm,浸泡于4%多聚甲醛缓冲液中,用于病理组织学检查;其余肝脏组织称重匀浆,检测超氧化物歧化酶(SOD)、谷胱甘肽(GSH)活性及丙二醛(MDA)含量。结果表明:在急、慢性肝损伤试验中,与模型组比较,黄连素组小鼠肝脏指数极显著降低(P<0.01),肝脏组织病变明显减轻。在急性肝损伤试验中,与模型组比较,黄连素组小鼠血清AST、ALT活性均极显著降低(P<0.01),肝脏中MDA含量显著降低(P<0.05),SOD、GSH活性均显著升高(P<0.05)。在慢性肝损伤试验中,与模型组比较,黄连素组小鼠血清AST活性极显著降低(P<0.01),ALT活性显著降低(P<0.05),MDA含量显著降低(P<0.05),肝脏中SOD、GSH活性均极显著升高(P<0.01)。说明黄连素可减轻肝损伤小鼠炎症程度并明显改善慢性肝损伤小鼠组织增生情况。

     

    Abstract: In order to explore the therapeutic effect and mechanism of berberine on carbon tetrachloride(CCl4)-induced liver injury, in the experiment, 80 healthy female Kunming mice were selected, 40 of which were used for acute liver injury test and 40 for chronic liver injury test. The mice were randomly divided into control group, model group, berberine group and silybin group, with 10 mice in each group. In acute liver injury test, mice in berberine group and silybin group were pretreated with berberine solution(25 mg/kg, by body weight) and silybin solution(50 mg/kg, by body weight) every day for 7 days, and then orally administered 0.6% CCl4(5 μL/g, by body weight) at one time. In the chronic liver injury test, 0.6% CCl4 solution(5 μL/g, by body weight) was given intragastric administration twice a week for 6 weeks. After the chronic liver injury model was successfully established, berberine group and silybin group were given berberine solution(weight 50 mg/kg) and silybin solution(50 mg/kg) daily for 30 days. The mice with acute liver injury and chronic liver injury were killed 24 hours after the last administration, orbital blood was collected, and sera were collected to detect aspartate aminotransferase(AST) and alanine aminotransferase(ALT) activities; the liver was weighed wet and the liver index was calculated. The left lobe of the liver about 1 cm × 1 cm × 0.25 cm was taken and immersed in 4% paraformaldehyde buffer for histopathological examination; the remaining liver tissues were weighed and homogenized, and the activities of superoxide dismutase(SOD), glutathione(GSH) and malondialdehyde(MDA) were detected. The results showed that in acute and chronic liver injury tests, compared with the model group, the liver index of berberine group was significantly decreased(P<0.01), and the pathological changes of liver tissue were significantly alleviated. In acute liver injury test, compared with the model group, the activities of AST and ALT in serum of berberine group were significantly decreased(P<0.01); the content of MDA in liver was significantly decreased(P<0.05), and the activities of SOD and GSH were significantly increased(P<0.05). In chronic liver injury test, compared with the model group, the serum AST activity in berberine group were significantly decreased(P<0.01); the ALT activity and MDA content were significantly decreased(P<0.05), and the activities of SOD and GSH in liver were significantly increased(P<0.01).The results suggested that berberine could reduce the degree of inflammation in mice with liver injury and significantly improve the tissue proliferation in mice with chronic liver injury.

     

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