基于转录组学探讨小红参对心力衰竭的影响和作用机制  

Effect of Rubia yunnanensis on heart failure and the underlying mechanism based on transcriptomics

作　　者：江小丽 李高一舟 程江豪 陈普 段小花 JIANG Xiaoli;LI Gaoyizhou;CHENG Jianghao;CHEN Pu;DUAN Xiaohua(Yunnan Key Laboratory of Dai and Yi Medicines,Yunnan University of Traditional Chinese Medicine,Yunnan Kunming 650500,China)

机构地区：[1]云南中医药大学云南省傣医药与彝医药重点实验室,云南昆明650500

出　　处：《中国医院药学杂志》2025年第2期173-180,共8页Chinese Journal of Hospital Pharmacy

基　　金：云南省兴滇英才支持计划“青年人才”(编号:XDYC-QNRC-2022-0284);国家中医药管理局高水平中医药重点学科建设项目“少数民族医学(傣医学)”(项目号:Zyyzdxk-2023193)。

摘　　要：目的:探讨小红参对小鼠心力衰竭的影响及作用机制。方法:取6只野生型C57 BL/6J为对照组,18只ApoE缺陷(ApoE-/-)小鼠随机分为模型组、治疗组和阳性对照组,给予高脂饮食建立心力衰竭模型。治疗组给予7.5 g·kg^(–1)小红参水煎液,阳性对照组给予曲美他嗪0.5 mg·kg^(–1)灌胃治疗;HF组给予灌胃等体积生理盐水。养殖12周后取心脏组织进行HE染色法检测小鼠心肌组织病理变化;Masson染色法检测小鼠心肌纤维化,天狼猩红染色法检测Ⅰ/Ⅲ胶原纤维百分比。而BNP作为衡量心力衰竭的金标准,通过RT-qPCR验证小鼠心脏组织中BNP的表达再次确认模型建立成功。提取心脏组织进行mRNA测序,分析差异基因,对差异基因进行GO、KEGG富集分析,通过RT-qPCR法验证差异基因mRNA表达,Western blot验证自噬通路蛋白。结果:与对照组相比,模型组细胞数量明显降低(P<0.05),模型组小鼠心肌纤维化和Ⅰ/Ⅲ胶原纤维百分比明显增加(P<0.05)。与模型组相比,治疗组和阳性对照组细胞数量明显增加(P<0.05),小鼠心肌纤维化和Ⅰ/Ⅲ胶原纤维百分比明显减少(P<0.05)。治疗组与模型组共有个197个差异基因,模型组与对照组之间共有205个差异基因,再次取交集有21个差异基因,其中有13个基因改变被治疗逆转,5个差异基因与心力衰竭相关:H2-Ab1、Ddit4、Mycn、Myl4、Nppa。RT-qPCR结果显示小红参可以逆转H2-Ab1、Ddit4、Mycn、Myl4、Nppa等基因在心力衰竭模型小鼠心脏组织中的表达。Western blot结果显示小红参可以降低LC3-Ⅰ,LC3-Ⅱ和P62蛋白表达。结论:小红参通过细胞因子-细胞因子受体的相互作用,趋化因子信号通路和自噬等通路调控差异基因H2-Ab1、Ddit4、Mycn、Myl4、Nppa和BNP的表达来改善小鼠心力衰竭。OBJECTIVE To investigate the effect of Rubia yunnanensis on heart failure(HF) in mice and the underlying mechanism.METHODS Six wild-type C57 BL/6J mice were taken as the control group,and 18 apoE-knockout(ApoE-/-) mice were randomly divided into the HF group,treatment group,and positive control group for establishing HF model via a highfat diet.Mice in the treatment group were given 7.5 g·kg^(–1) Rubia yunnanensis decoction,and those in the positive control group were given oral gavage of trimetazidine 0.5 mg·kg^(–1).Mice in the HF group were given an equal volume of saline by gavage.After feeding for 12 weeks,heart tissues were taken for H&E staining to detect the myocardial tissue changes.Myocardial fibrosis was detected by Masson's trichrome staining,and type Ⅰ/Ⅲ collagen ratio was detected by Sirius red staining.The positive expression of brain natriuretic peptide(BNP) served as the golden standard for HF,which was measured in mouse heart to validate the success of modeling.Heart tissue was extracted for mRNA sequencing,and differentially expressed genes(DEGs) were subjected to GO and KEGG enrichment analyses.The mRNA expressions of DEGs were verified by real-time reverse transcriptase-polymerase chain reaction(RT-qPCR).Protein levels of autophagy markers were detected by Western blot.RESULTS Compared with the control group,cell number in the model group was significantly lower(P<0.05),and the myocardial fibrosis and type Ⅰ/Ⅲ collagen ratio were significantly higher(P<0.05).Compared with the model group,cell number in the treatment and the positive control groups was significantly higher(P<0.05),and myocardial fibrosis and type Ⅰ/Ⅲ collagen ratio were significantly lower(P<0.05).There were 197 DEGs in the treatment group versus the model group,205 DEGs in the model group versus the control group,and 21 DEGs in their intersection.Among them,expression levels of 13 DEGs were altered by the treatment of Rubia yunnanensis,involving 5 associated with HF:H2-Ab1,Ddit4,Mycn,Myl4,and Nppa.RTqPCR show

关 键 词：小红参 心力衰竭 心肌纤维化 转录组学 

分 类 号：R965[医药卫生—药理学]