摘要
目的:通过体内、外实验研究益气逐瘀解毒颗粒(YQZYJD)调控相关长链非编码RNA(long non-coding RNA,LncRNA)的表达抗肝纤维化的作用。方法:体内实验采用CCl_(4)构建小鼠肝纤维化模型,给予YQZYJD灌胃治疗8周;体外实验分离、诱导原代肝星状细胞(Primary hepatic stellate cells,p-HSCs)活化,给予YQZYJD水提物干预120h。结果:与模型对照组相比,YQZYJD显著降低小鼠肝组织纤维化程度,YQZYJD组α1-Ⅰ型胶原基因(Collagen typeⅠalpha 1,COL1α1)、α-平滑肌肌动蛋白(alpha smooth muscle Actin,α-SMA)蛋白水平显著降低(P<0.01),肺腺癌相关转录本1(Metastasis-Associated Lung Adenocarcinoma Transcript 1,Malat1)、同源盒转录反义RNA(Homeobox transcript antisense RNA,Hotair)、核旁装配转录本1(Nuclear paraspeckle assembly transcript 1,Neat1)mRNA的表达显著降低(P<0.05或P<0.01),母系表达基因3(Maternally expressed gene 3,Meg3)、信息沉默调节因子1(Silent information regulator 1,Stirt1)mRNA表达显著升高(P<0.01);此外,p-HSCs经YQZYJD处理120h后,YQZYJD组Malat1、Hotair mRNA表达降低,Neat1mRNA表达升高,Meg3mRNA表达降低,Stirt1mRNA表达显著升高(P<0.01),YQZYJD组COL1α1、α-SMA蛋白表达显著降低(P<0.01)。结论:YQZYJD可通过上调具有抑制HSCs活化作用的Meg3表达,下调促进HSCs活化作用的Hotair、Malat1表达,减少其对Stirt1的靶向作用,发挥抗肝纤维化的作用。
Objective:The objective of this study is to investigate the effect of YQZYJD on regulating the expression of long non-coding RNA(LncRNA)on liver fibrosis through in vivo and in vitro experiments.Methods:In vivo experiments were conducted by administering YQZYJD via gavage for 8 weeks to a mouse liver fibrosis model induced by CCl_(4).In vitro experiments were conducted by isolating and inducing the activation of primary hepatic stellate cells(p-HSCs)and administering YQZYJD aqueous extract for 120 h.Results:Compared with the model control group,YQZYJD significantly reduced the levels ofα1-collagen typeⅠalpha 1(COL1α1),α-smooth muscle actin(α-SMA),and lung adenocarcinoma-associated transcript 1(P<0.01).Moreover,YQZYJD significantly reduced the expression of Metastasis-Associated Lung Adenocarcinoma Transcript 1(Malat1),Homeobox transcript antisense RNA(Hotair),and Nuclear paraspeckle assembly transcript 1(Neat1)(P<0.01).The expression of maternally expressed gene 3(Meg3)and Silent information regulator 1(Stirt1)mRNA,which have inhibitory effects on the activation of HSCs,was significantly increased(P<0.01),while the expression of Neat1 mRNA,which promotes the activation of HSCs,was significantly reduced(P<0.05 or P<0.01).Additionally,after 120 h of treatment of p-HSCs with YQZYJD,the mRNA expression of Malat1 and Hotair was decreased,the mRNA expression of Neat1 was increased,and the mRNA expression of Meg3 was decreased.The targeting effect of Hotair and Malat1 on Stirt1 was reduced(P<0.01),and the protein expression of COL1α1 andα-SMA was significantly decreased in the YQZYJD group(P<0.01).Conclusion:YQZYJD can exert anti-liver fibrosis effects by up-regulating the expression of Meg3,which has an inhibitory effect on the activation of HSCs,and down-regulating the expression of Hotair and Malat1,which promote the activation of HSCs,and reducing their targeting effect on Stirt1.
作者
邓秀秀
李晖
张泽凤
陈婧
曾子键
董海舰
陶雨静
郭佳玲
DENG Xiuxiu;LI Hui;ZHANG Zefeng(Central Laboratory,Hospital of Chengdu University of Traditional Chinese Medicine,Chengdu Sichuan 610072,China;Chengdu Pidu District Hospital of Traditional Chinese Medicine,Chengdu Sichuan 611730,China)
出处
《四川中医》
2023年第4期43-48,共6页
Journal of Sichuan of Traditional Chinese Medicine
基金
四川省科技厅项目资助(编号:2020YFS0379:益气逐瘀解毒颗粒改善肝脏微环境逆转小鼠肝纤维化的机制研究,负责人:李晖)
作者简介
第一作者:邓秀秀,硕士,医师,研究方向:中西医结合临床,E-mail:861785267@qq.com;通讯作者:李晖,博士,教授,研究方向:肝纤维化的中西医结合防治,E-mail:1400124746@qq.com。
