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侧脑室注射miR-7通过EGFR/STAT3途径抑制大鼠脑出血后脑损伤 被引量:11
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作者 钱红 胡柯 +5 位作者 谢明 武衡 李文军 武斌 满荣勇 聂萌 《细胞与分子免疫学杂志》 CAS CSCD 北大核心 2018年第2期141-147,共7页
目的观察微小RNA-7(miR-7)对大鼠脑出血后脑损伤的影响,并探讨其分子机制。方法选取75只SD大鼠,以Ⅶ型胶原酶注入苍白球构建脑出血模型,随机分为对照组、miR-7激动剂(miR-7 agomir)组、miR-7激动剂对照(agomir control)组、miR-7拮抗剂(... 目的观察微小RNA-7(miR-7)对大鼠脑出血后脑损伤的影响,并探讨其分子机制。方法选取75只SD大鼠,以Ⅶ型胶原酶注入苍白球构建脑出血模型,随机分为对照组、miR-7激动剂(miR-7 agomir)组、miR-7激动剂对照(agomir control)组、miR-7拮抗剂(miR-7 antagomir)组和miR-7拮抗剂对照(antagomir control)组,每组15只。造模后第2天通过侧脑室分别注射10μL的生理盐水、miR-7 agomir、agomir control、miR-7 antagomir、antagomir control,造模后第7天进行神经功能评分,然后处死动物,取出脑组织,HE染色观察脑组织病理改变,干湿重法测定脑组织含水量,荧光实时定量PCR检测血肿周围脑组织中miR-7、胶质纤维酸性蛋白(GFAP)和表皮生长因子受体(EGFR)表达,Western blot法分析血肿周围脑组织中GFAP、EGFR、信号转导子和转录激活子3(STAT3)、磷酸化STAT3(p-STAT3)水平。生物信息学预测miR-7与EGFR的靶向结合情况,构建野生型荧光素酶报告基因载体及相应的突变载体,与miR-7模拟物(mimic)共转染HEK293T细胞,检测荧光素酶活性。结果与对照组相比,miR-7 agomir明显增加血肿周围脑组织miR-7水平,减轻脑组织病理损害,减少神经功能评分和脑组织含水量,并降低血肿周围脑组织GFAP、EGFR表达水平及p-STAT3/STAT3比值;miR-7 antagomir的作用则相反。相应阴性对照物对上述指标无影响。生物信息学分析发现EGFR的3'-非翻译区存在miR-7结合位点,而且miR-7 mimic明显降低野生型EGFR荧光素酶活性,但对突变型无影响。结论 miR-7通过抑制EGFR/STAT3信号通路拮抗星形胶质细胞活化,从而减轻大鼠脑出血后脑损伤。 展开更多
关键词 微小RNA-7(miR-7) 表皮生长因子受体(EGFR) 信号转导子和转录激活子3(STAT3) 胶质纤维酸性蛋白(GFAP) 脑出血
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基于网络药理学和实验验证探讨苦参治疗乙型病毒性肝炎的作用机制 被引量:3
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作者 龙飘 房盛懿 +3 位作者 杨雨莹 欧阳丹 满荣勇 曹建中 《湖南中医药大学学报》 CAS 2022年第2期271-277,共7页
目的基于网络药理学和分子对接技术,探讨苦参治疗乙型病毒性肝炎的作用机制,为临床防治提供指导。方法通过GeneCards、OMIM和TTD数据库获取乙型病毒性肝炎靶点,使用TCMSP、BATMAN-TCM、ETCM、HERB数据库及查阅相关文献获取苦参活性成分... 目的基于网络药理学和分子对接技术,探讨苦参治疗乙型病毒性肝炎的作用机制,为临床防治提供指导。方法通过GeneCards、OMIM和TTD数据库获取乙型病毒性肝炎靶点,使用TCMSP、BATMAN-TCM、ETCM、HERB数据库及查阅相关文献获取苦参活性成分及靶点,并利用VENNY作图取两者的交集。用Cytoscape、STRING构建"活性成分-潜在靶点"网络图和蛋白互作网络图;应用DAVID数据库进行GO和KEGG通路的富集分析;最后通过分子对接和qPCR对上述结果进行验证。结果乙型病毒性肝炎靶标1827个,苦参活性成分39个,主要成分为刺芒柄花素、8-isopentenyl-kaempferol、(2R)-7-hydroxy-2-(4-hydroxyphenyl)chroman-4-one、高丽槐素、氧化苦参碱;苦参干预乙型病毒性肝炎共同靶点64个,其核心靶点为IL-6、AKT1、VEGFA、PTGS2、JUN、CASP3、TNF和MAPK1;KEGG富集得到通路111条,包括癌症的通路、乙型肝炎和TNF信号通路;分子对接技术显示氧化苦参碱与TNF、IL-6结合,结合能为-6.1~-9.8 kcal·mol;体外实验证实氧化苦参碱可下调HepG2.2.15细胞中TNF-α、IL-6 mRNA的表达,且随着剂量的增加,下调趋势更显著。结论苦参具有多成分、多靶点特性,其主要成分氧化苦参碱可通过激活TNF信号通路,下调TNF-α、IL-6 mRNA的表达,控制肝脏炎症,抑制HBV复制。 展开更多
关键词 苦参 乙型病毒性肝炎 网络药理学 实验验证 作用机制
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Clinical efficacy and safety of TCM prescriptions combined with nucleoside(acid)analogues in treating chronic hepatitis B:a meta-analysis 被引量:1
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作者 XIA Yu LI Xin +2 位作者 man rongyong WANG Aibing CAO Jianzhong 《Digital Chinese Medicine》 2021年第3期170-179,共10页
Objective There are many clinical reports on traditional Chinese medicine(TCM)combined with nucleoside(acid)analogues(NAs)for the treatment of chronic hepatitis B(CHB),but its efficacy and safety are not completely cl... Objective There are many clinical reports on traditional Chinese medicine(TCM)combined with nucleoside(acid)analogues(NAs)for the treatment of chronic hepatitis B(CHB),but its efficacy and safety are not completely clear.This meta-analysis aims to evaluate the clinical efficacy and safety thus providing evidence for clinical applications.Methods We searched Chinese databases the China National Knowledge Infrastructure(CNKI),Wanfang Data,and China Science and Technology Journal Database(VIP),as well as English databases Pub Med and Cochrane Library,from time of establishment to April 14,2021.Literature quality was evaluated according to the bias risk assessment criteria of Cochrane Collaboration network.Rev Man 5.3 and Stata 12.0 software were used to perform this research.Results A total of 23 articles,3282 patients,and 25 TCM prescriptions were included in this study.NAs plus TCM remarkably improved the clinical total effective rate[Odds ratio(OR)=3.92,P<0.00001],TCM syndrome score(Mean difference=-3.73,P<0.00001),hepatitis B virus(HBV)DNA negative conversion rate(OR=1.49,P=0.0001),hepatitis Be antigen(HBe Ag)negative conversion rate(OR=2.03,P<0.00001),alanine aminotransferase levels[Std mean difference(SMD)=-0.95,P<0.00001],and aspartate aminotransferase levels(SMD=-0.70,P=0.0004).Adverse reaction rates did not increase in the combined treatment group(OR=0.97,P=0.84).A comprehensive analysis of the 25 TCM prescriptions suggested that the combination of spleen-strengthening prescriptions with NAs showed better effects than other prescriptions.Conclusion TCM in combination with NAs,demonstrated better clinical efficacy against CHB than NAs alone.In addition,the combination of spleen-strengthening prescriptions and NAs was identified as the best therapeutic strategy.However,more randomized controlled trials of high quality are needed to provide more reliable clinical basis for the application of TCM. 展开更多
关键词 Traditional Chinese medicine(TCM)prescriptions Spleen-strengthening prescriptions Nucleoside(acid)analogues(NAs) Complementary and alternative medicine Chronic hepatitis B(CHB) META-ANALYSIS
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