基于JAK3/STAT1信号通路探讨解毒化瘀颗粒改善急性肝衰竭大鼠肝损伤的作用机制OA
Exploring the effect of Jiedu Huayu Granule(解毒化瘀颗粒)on liver injury in acute liver fail-ure rats via JAK3/STAT1 signaling pathway
目的 探讨JAK3/STAT1信号通路中解毒化瘀颗粒对ALF大鼠肝损伤的干预作用.方法 将92只SPF级SD雄性大鼠随机分为正常组20只、模型组36只、中药组36只.采用D-Galn/LPS构建ALF大鼠模型.正常组予蒸馏水灌胃,中药组在造模前72 h予解毒化瘀颗粒溶剂灌胃.观察24 h内的存活率,收集血清及肝组织样本,生化分析仪检测ALT、AST、TBIL,凝血酶仪检测PT,ELISA 检测TNF-α、IL-6,Western blot检测JAK3、STAT1蛋白相对表达水平,qPCR检测JAK3、STAT1 mRNA相对表达水平,光镜下观察肝组织病理,透镜下观察肝线粒体、内质网等超微改变.结果 与正常组相比,模型组的肝细胞呈现坏死,肝线粒体及内质网结构被破坏,大鼠存活率下降(P<0.05),肝功能指标、凝血功能指标、炎症水平、JAK3和STAT1 mRNA的相对表达水平及蛋白相对表达水平显著升高(P<0.01),肝线粒体显著减少(P<0.01);与模型组相比,中药组的肝细胞得到修复,肝线粒体及内质网结构得到恢复,大鼠存活率提高(P<0.05),凝血功能、JAK3和STAT1蛋白相对表达水平下降(P<0.05),肝功能指标、炎症水平、JAK3和STAT1 mRNA的相对表达水平显著下降(P<0.01),肝线粒体显著增加(P<0.01).结论 解毒化瘀颗粒可能通过JAK3/STAT1信号通路抑制炎症反应、改善线粒体功能障碍、减轻内质网应激,从而修复ALF大鼠受损肝脏.
Objective To explore the interventional effect of Jiedu Huayu Granule(解毒化瘀颗粒,JDHYG)on liver injury in acute liver failure(ALF)rats and its effect on the JAK3/STAT1 signaling pathway.Methods 92 SPF-grade male SD rats were randomly divided into the normal group(20 rats),model group(36 rats),and JDHYG group(36 rats).The ALF rat model was established by using D-Galn/LPS,the normal group was given distilled water by gavage,and JDHYG group was given JDHYG solvent by gavage 72 hours before modeling.The survival rate of rats within 24 hours was observed.Serum and liver tissue samples were collected.ALT,AST,TBIL levels were detected by automatic biochemical analyzer,PT by a coagulometer,TNF-α and IL-6 by ELISA,the relative protein expression levels of JAK3 and STAT1 levels by Western blot,and the relative mRNA expression levels of JAK3 and STAT1 by qPCR.Liver tissue pathology was observed by optical microscope,and ultrastructural changes of mitochondria and endoplasmic reticulum by transmission electron microscope.Results Compared with the normal group,the liver cells in the model group showed necrosis,the structures of liver mitochondria and endoplasmic reticulum were damaged,and the survival rate of rats decreased(P<0.05).The levels of liver function,coagulation function,inflammatory response,the relative mRNA expression levels of JAK3 and STAT1,and the relative pro-tein expression levels were significantly increased(P<0.01),and liver mitochondria significantly decreased(P<0.01).Com-pared with the model group,the liver cells in the JDHYG group were repaired,the structures of liver mitochondria and endoplasmic reticulum were restored,the survival rate of rats increased(P<0.05).The levels of coagulation function,the rela-tive protein expression levels of JAK3 and STAT1 decreased(P<0.05).The levels of liver function,inflammatory levels,the relative mRNA expression levels of JAK3 and STAT1 significantly decreased(P<0.01),and liver mitochondria significantly increased(P<0.01).Conclusion JDHYG may inhibit inflammatory response,improve mitochondrial dysfunction,alleviate endoplasmic reticulum stress through the JAK3/STAT1 signaling pathway,thereby repairing the damaged liver in ALF rats.
潘李轶;陈月桥;陈玉;黄钰雯;裴浩;吴亚林;吴凤兰;叶绿萍;王娜
广西中医药大学,广西 南宁 530000广西中医药大学第一附属医院,广西 南宁 530000广西中医药大学,广西 南宁 530000广西中医药大学,广西 南宁 530000广西中医药大学,广西 南宁 530000广西中医药大学,广西 南宁 530000广西中医药大学,广西 南宁 530000广西中医药大学第一附属医院,广西 南宁 530000广西中医药大学第一附属医院,广西 南宁 530000
医药卫生
解毒化瘀颗粒JAK3/STAT1信号通路急性肝衰竭炎症反应线粒体内质网
Jiedu Huayu Granule(解毒化瘀颗粒)JAK3/STAT1 signaling pathwayAcute liver failureInflammationMitochondriaEndoplasmic reticulum
《时珍国医国药》 2026 (11)
2015-2021,7
国家自然科学基金(82160888)广西自然科学基金(2022GXNSFAA035573)
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