摘要
目的:观察解毒护肝方对药物性肝损伤大鼠JAK2/STAT3通路的干预作用。方法:大鼠随机分为:模型对照组、水飞蓟宾44.1 mg/kg组、解毒护肝方15.8、31.5、63 g/kg组,另设空白对照组。对乙酰氨基酚造模同时,分别灌胃给予相应药物或生理盐水,连续30日,生化法检测血清谷草转氨酶(AST)、谷丙转氨酶(ALT)、总胆红素(T-BIL)、直接胆红素(D-BIL)的变化,用酶标仪检测血清白介素13(IL-13)、白介素22(IL-22)、白介素6(IL-6)的含量;HE染色观察肝组织病理形态;RT-PCR和Western-blot技术检测肝组织中STAT3的基因、蛋白表达情况以及p-STAT3蛋白表达情况;免疫组化法观察肝组织p-JAK2的表达。结果:与正常组比较,模型组大鼠血清AST、ALT活性及D-BIL含量均显著升高,血清IL-13水平显著升高,肝脏p-STAT3和p-JAK2蛋白表达明显上调。与模型组比较,解毒护肝方15.8 g生药/kg、31.5 g生药/kg组能明显降低血清AST、ALT活性及D-BIL含量,对肝细胞病理形态具有一定的保护作用。解毒护肝方31.5 g生药/kg、63 g生药/kg组能显著下调肝组织p-STAT3和p-JAK2蛋白表达水平。结论:解毒护肝方各剂量组能不同程度地防治对乙酰氨基酚所致的肝损伤,但结合临床安全、有效的用药原则,以31.5 g生药/kg组效果较好,其护肝作用可能通过调节JAK2/STAT3途径来实现。
Objective:To observe the effect of Jiedu Hugan decoction on drug-induced liver injury by JAK2/STAT3 pathway in rats.Methods:Rats were randomly divided into the model group,44.1 mg/kg silibinin group,Jiedu Hugan decoction groups(15、31.5、63 g raw drug/kg)and the control group.Liver injury model was established by acetaminophen,corresponding drug or saline water was given for 30 days.After administration,levels of serum alanine transaminase(ALT),aspartate transaminase(AST),direct bilirubin(DBIL)and total bilirubin(TBIL)were detected by Automatic Biochemistry Analyzer.Contents of Interleukin 6(IL-6),Interleukin 13(IL-13),and Interleukin 22(IL-22)were measured by enzyme mark instrument.Histopathological changes of liver tissues were examined by HE staining.The mRNA expression levels of signal transducer and activator of transcription 3(STAT3)were determined by RT-PCR.The protein expression levels of STAT3 and p-STAT3 were detected by Western blot analysis.The expression of p-JAK2 in the liver tissue was observed by immunohistochemistry.Results:Compared with the control group,the levels of ALT,AST,DBIL and serum IL-13 were increased in the model group,protein expressions of p-STAT3 and p-JAK2 in liver tissues were up regulated.Compared with the model group,the activities of AST、ALT and D-BIL level was significantly decreased in Jiedu Hugan decoction groups(15.75 g/kg,31.5 g/kg),and pathological changes of liver cells were improved.In 31.5 g/kg and 63 g/kg Jiedu Hugan decoction groups groups,the expressionws of p-STAT3 and p-JAK2 in liver tissues were significantly reduced.Conclusion:Jiedu Hugan decoction has the protective effect on liver injury induced by acetaminophen.31.5 g/kg Jiedu Hugan decoction has advantage in clinical safety and effect,its mechanism may be related to regulating the STAT3/JAK2 pathway.
作者
王茜
郝蕾
韩雪
储心乔
石铖
郭秋红
张一昕
Wang Xi;Hao Lei;Han Xue;Chu Xinqiao;Shi Cheng;Guo Qiuhong;Zhang Yixin(HeBei University of Chinese Medicine,Hebei Higher Education Institute Applied Technology Research Center on TCM Formula Preparation,Shijiazhuang 050200)
出处
《中药药理与临床》
CAS
CSCD
北大核心
2019年第6期144-149,共6页
Pharmacology and Clinics of Chinese Materia Medica
基金
国家自然科学基金资助项目(81503268)
河北省高等学校科学技术研究青年拔尖计划项目(BJ2016038)
中央财政公共卫生专项"2017年中药资源普查项目(Z135080000022)".
作者简介
通信作者:张一昕,教授,主要从事中药及其复方药效机制研究,E-mail:hbzyx123@163.com。
