四君子汤治疗肝硬化的转录学机制分析  

Mechanism of Sijunzi decoction in treatment of liver cirrhosis based on transcriptomic sequencing

作　　者：闵筱辉[1] 覃延翔 黎洁瑶[1] 陈其奎[1] 萧焕明[2] 许稷豪 Min Xiaohui;Qin Yanxiang;Li Jieyao;Chen Qikui;Xiao Huanming;Xu Jihao(Department of Gastroenterology,Sun Yat-sen Memorial Hospital of Sun Yat-sen University,Guangzhou 510120,China)

机构地区：[1]中山大学孙逸仙纪念医院消化内科,广州510120 [2]广东省中医院肝病科,广州510120

出　　处：《新医学》2021年第11期819-826,共8页Journal of New Medicine

基　　金：国家自然科学基金(81970464);国家“十三五”重大专项课题(2018ZX10725506-033);广东省自然基金基础与应用基础研究专项(2016A030313316);广州市科技计划项目民生科技攻关计划(201903010064)。

摘　　要：目的探讨四君子汤改善肝硬化病理改变的作用,并且研究四君子汤对肝细胞的转录组学改变情况,探索潜在的分子作用机制。方法采用四氯化碳(CCl_(4))诱导大鼠产生肝硬化,并用标准剂量的四君子汤灌胃治疗肝硬化大鼠12周,通过肝组织HE染色、Masson染色,从病理学改变评估四君子汤治疗肝硬化效果。随后采取Illumnia高通量测序,同步对转录组学测序结果筛选差异表达基因(DEG),并进行生物聚类分析、KEGG信号通路聚类分析。结果与正常SD大鼠相比,CCl_(4)诱导的肝硬化SD大鼠肝组织出现广泛的假小叶,转录组学测序共筛选出402个DEG。GO富集分析发现DEG主要富集于细胞周期相关生物学功能。KEGG分析提示DEG明显富集于细胞增殖、分化通路。CCl_(4)诱导肝硬化大鼠在经过四君子汤治疗后,肝脏组织中的假小叶明显减少,共有411个DEG。GO以及KEGG分析提示DEG分别富集于细胞周期生物学功能以及细胞增殖、肿瘤相关信号通路。结论四君子汤可有效缓解CCl_(4)所诱导的肝硬化,其中细胞增殖相关Wnt通路受到明显调控,可能是四君子汤治疗肝硬化的分子机制。Objective To investigate the effect and molecular mechanism of Sijunzi decoction on the pathological changes of CCl_(4)-induced liver cirrhosis(LC) and evaluate the role of Sijunzi decoction in the transcriptomic changes of liver cells. Methods SD rats were treated with CCl_(4) to induce LC and given with standard dose of Sijunzi decoction for 12 weeks by gavage. The efficacy of Sijunzi decoction in the treatment of LC was assessed according to pathological changes by HE and Masson staining. The deferentially-expressed genes(DEGs) in CCl_(4)-induced LC rats were identified using Illumina Hiseq sequencing system. The gene ontology(GO) and pathway enrichment analyses were performed in the DAVID and KEGG pathway databases, respectively. Results Compared with the SD wild-type rats, CCl_(4)-induced LC rats presented with multiple liver fibrous septa and cirrhotic nodules. The treatment of Sijunzi decoction significantly reduced liver fiber interval and degeneration degree in CCl_(4)-induced LC rats. A total of 402 DEGs were identified between the wild-type and CCl_(4)-induced LC rats. GO enrichment analysis demonstrated that the DEGs were mainly enriched in cell cycle-associated biological function. The KEGG pathway enrichment analysis revealed that the DEGs were significantly associated with cell proliferation-and cell division-associated signaling pathways. Similarly, Sijunzi decoction treatment led to 411 DEGs in the liver of LC rats. GO and KEGG analyses revealed that those DEGs were significantly enriched in the cell cycle process and cell proliferation-and tumor-associated signaling pathways, respectively. Conclusion Sijunzi decoction effectively attenuates CCl_(4)-induced LC in rat models by regulating the cell proliferation-associated Wnt signaling pathway, which is probably the underlying mechanism.

关 键 词：肝硬化 四君子汤 转录组学 细胞增殖 

分 类 号：R285.5[医药卫生—中药学]