本文選題：類風(fēng)濕關(guān)節(jié)炎 + 實(shí)驗(yàn)性關(guān)節(jié)炎　； 參考：《安徽醫(yī)科大學(xué)》2017年博士論文

【摘要】：類風(fēng)濕關(guān)節(jié)炎(rheumatoid arthritis,RA)是一種全身性、自身免疫性疾病,以慢性炎癥、滑膜細(xì)胞異常增生、關(guān)節(jié)腫脹與壓痛為其臨床特征,可導(dǎo)致關(guān)節(jié)功能受限、工作能力喪失,給患者和社會(huì)帶來(lái)沉重的負(fù)擔(dān)。RA好發(fā)于35~50歲人群,女性發(fā)病率約為男性2~3倍。目前,RA具體發(fā)病機(jī)制尚不清楚,認(rèn)為可能與免疫因素、環(huán)境因素、遺傳等有關(guān)。因此,積極探索RA的發(fā)病機(jī)制,尋找潛在診斷標(biāo)志物具有重要的理論與現(xiàn)實(shí)意義。以前關(guān)于RA機(jī)制的研究主要集中在編碼基因。近年來(lái),越來(lái)越多的研究表明長(zhǎng)期以來(lái)被視為“噪音”和“暗物質(zhì)”的非編碼RNAs(non-coding RNAs,nc RNAs),具有復(fù)雜的生物學(xué)功能。nc RNAs中的長(zhǎng)鏈非編碼RNAs(long non-coding RNAs,Lnc RNAs)是由基因組中非編碼序列轉(zhuǎn)錄生成的、長(zhǎng)度大于200nt、不具有翻譯成蛋白質(zhì)能力的轉(zhuǎn)錄本,在表觀遺傳水平、轉(zhuǎn)錄水平、翻譯水平、蛋白修飾過(guò)程中均可發(fā)揮重要的調(diào)控作用,與多種疾病密切相關(guān)。但目前對(duì)RA發(fā)生、發(fā)展過(guò)程中Lnc RNAs的調(diào)控作用仍知之甚少。目前,西醫(yī)臨床上對(duì)于RA的治療,主要以減輕疼痛、控制癥狀為主,長(zhǎng)期應(yīng)用副反應(yīng)明顯,患者多不能耐受或依從性差,遠(yuǎn)程療效不理想。因此,從傳統(tǒng)中藥中開發(fā)治療RA的藥物,越來(lái)越受到重視。黃芪為豆科植物蒙古黃芪Astragalus membranaceus(Fisch.)Bge.var.mongolicus(Bge.)Hsiao或膜莢黃芪Astragalus membranaceus(Fisch.)Bge.的干燥根,具有行滯通痹、補(bǔ)氣升陽(yáng)、利水消腫等功效,為中醫(yī)臨床實(shí)踐中常用藥材。黃芪總皂苷(Astragalosides,AST)是黃芪的有效部位群,主要含有黃芪皂苷I~VIII等�，F(xiàn)代藥理學(xué)研究表明,AST具有抗炎、抗氧化、免疫調(diào)節(jié)、抗衰老等多種藥理作用。本課題擬在課題組前期研究的基礎(chǔ)上,開展如下研究:(1)實(shí)驗(yàn)性關(guān)節(jié)炎相關(guān)長(zhǎng)鏈非編碼RNAs的篩選及黃芪總皂苷的干預(yù)作用;(2)基于Lnc RNA-mi RNA-m RNA共表達(dá)網(wǎng)絡(luò)篩選實(shí)驗(yàn)性關(guān)節(jié)炎發(fā)病過(guò)程中關(guān)鍵Lnc RNAs;(3)Lnc RNA S56464.1靶向mi R-152/Wnt通路誘導(dǎo)成纖維樣滑膜細(xì)胞(fibroblast-like synoviocytes,FLS)增殖及黃芪總皂苷干預(yù)作用等研究,以期系統(tǒng)、深入地揭示Lnc RNAs在實(shí)驗(yàn)性關(guān)節(jié)炎發(fā)生、發(fā)展中所扮演的角色及黃芪總皂苷的干預(yù)作用,從Lnc RNAs的角度揭示實(shí)驗(yàn)性關(guān)節(jié)炎的發(fā)病機(jī)理,并闡明黃芪總皂苷治療實(shí)驗(yàn)性關(guān)節(jié)炎的可能機(jī)制。第一部分實(shí)驗(yàn)性關(guān)節(jié)炎相關(guān)長(zhǎng)鏈非編碼RNA的篩選及黃芪總皂苷的干預(yù)作用目的:篩選實(shí)驗(yàn)性關(guān)節(jié)炎發(fā)病過(guò)程中差異表達(dá)的長(zhǎng)鏈非編碼RNA(long non-coding RNAs,Lnc RNAs),探討實(shí)驗(yàn)性關(guān)節(jié)炎可能的發(fā)病機(jī)制及黃芪總皂苷可能的作用靶點(diǎn)。方法:采用大鼠Lnc RNA基因芯片檢測(cè)佐劑性關(guān)節(jié)炎(adjuvant arthritis,AA)大鼠滑膜組織中Lnc RNAs/m RNAs表達(dá)情況,以Fold change值1.5,P-value0.05篩選差異表達(dá)基因,進(jìn)行基因本體論(Gene Ontology,GO)和信號(hào)通路(Pathway)分析,構(gòu)建差異表達(dá)基因Lnc RNA-m RNA共表達(dá)網(wǎng)絡(luò),篩選關(guān)鍵差異Lnc RNAs并采用實(shí)時(shí)熒光定量PCR技術(shù)對(duì)其進(jìn)行驗(yàn)證。結(jié)果:正常組和模型組共篩選出260個(gè)差異表達(dá)的LncRNAs,其中模型組中上調(diào)Lnc RNAs表達(dá)譜數(shù)據(jù)170個(gè),下調(diào)Lnc RNAs表達(dá)譜數(shù)據(jù)90個(gè);獲得675個(gè)差異表達(dá)的m RNAs,模型組中上調(diào)m RNAs表達(dá)譜數(shù)據(jù)422個(gè),下調(diào)m RNAs表達(dá)譜數(shù)據(jù)253個(gè);共獲得4163個(gè)GO條目,其中上調(diào)差異基因富集于2494個(gè)GO條目,下調(diào)差異基因富集于1669個(gè)GO條目;獲得42條與差異基因相關(guān)的信號(hào)通路,其中上調(diào)差異基因富集于25條信號(hào)通路,下調(diào)差異基因富集于17條信號(hào)通路;6個(gè)關(guān)鍵Lnc RNAs(XR_008357,U75927,MRAK046251,XR_006457,DQ266363和MRAK003448)實(shí)時(shí)熒光定量PCR檢測(cè)結(jié)果與基因芯片的結(jié)果相一致。正常組、模型組和AST組共篩選出75個(gè)差異表達(dá)的LncRNAs,與正常組和AST組相比,模型組上調(diào)Lnc RNAs表達(dá)譜數(shù)據(jù)41個(gè),下調(diào)Lnc RNAs表達(dá)譜數(shù)據(jù)34個(gè);篩選出247個(gè)差異表達(dá)的m RNAs,模型組中上調(diào)m RNAs表達(dá)譜數(shù)據(jù)171個(gè),下調(diào)m RNAs表達(dá)譜數(shù)據(jù)76個(gè);共獲得135個(gè)GO條目,其中上調(diào)差異基因富集于117個(gè)GO條目,下調(diào)差異基因富集于18個(gè)GO條目;共獲得17條與差異基因相關(guān)的信號(hào)通路,其中上調(diào)差異基因富集于14條信號(hào)通路,下調(diào)差異基因富集于3條信號(hào)通路;4個(gè)關(guān)鍵Lnc RNAs(MRAK012530、MRAK132628、MRAK003448、XR_00645)實(shí)時(shí)熒光定量PCR檢測(cè)結(jié)果與基因芯片的結(jié)果相一致。結(jié)論:LncRNAs在實(shí)驗(yàn)性關(guān)節(jié)炎發(fā)病過(guò)程中存在差異表達(dá),AST防治實(shí)驗(yàn)性關(guān)節(jié)炎的機(jī)制可能與調(diào)控差異表達(dá)的Lnc RNAs有關(guān)。第二部分基于Lnc RNA-mi RNA-m RNA共表達(dá)網(wǎng)絡(luò)篩選實(shí)驗(yàn)性發(fā)病過(guò)程中關(guān)鍵Lnc RNAs目的:篩選實(shí)驗(yàn)性關(guān)節(jié)炎發(fā)病過(guò)程中關(guān)鍵Lnc RNAs,探討其可能的發(fā)病機(jī)制。方法:mi RNAs基因表達(dá)譜數(shù)據(jù)來(lái)源于美國(guó)國(guó)立生物信息中心高通量基因表達(dá)數(shù)據(jù)庫(kù)和已發(fā)表文獻(xiàn),Lnc RNAs/m RNAs基因表達(dá)譜數(shù)據(jù)來(lái)源于課題組前期已發(fā)表文章;以差異倍數(shù)2和P-value0.05為標(biāo)準(zhǔn),篩選差異表達(dá)的Lnc RNAs、mi RNAs和m RNAs;借助miranda和targetscan預(yù)測(cè)差異mi RNAs靶向的m RNAs,借助RNAhybrid預(yù)測(cè)差異mi RNAs靶向的Lnc RNAs;將mi RNAs靶向的Lnc RNAs和m RNAs,分別與差異Lnc RNAs和m RNAs合并,取交集,得到共表達(dá)Lnc RNAs和m RNAs;以共表達(dá)Lnc RNAs、m RNAs和差異mi RNAs為基礎(chǔ),構(gòu)建Lnc RNA-mi RNA-m RNA共表達(dá)網(wǎng)絡(luò),并進(jìn)行功能信息學(xué)分析,篩選實(shí)驗(yàn)性關(guān)節(jié)炎發(fā)病過(guò)程中關(guān)鍵Lnc RNAs。結(jié)果:Lnc RNA-mi RNA-m RNA共表達(dá)網(wǎng)絡(luò)由7個(gè)Lnc RNAs節(jié)點(diǎn),24個(gè)mi RNAs節(jié)點(diǎn),90個(gè)m RNAs節(jié)點(diǎn),301個(gè)邊緣組成;功能信息學(xué)分析結(jié)果表明,差異基因主要富集于147個(gè)GO條目,23條信號(hào)通路;LncRNA S56464.1,LncRNA XR_006437.1和LncRNA J01878被鑒定為實(shí)驗(yàn)性關(guān)節(jié)炎發(fā)病過(guò)程中的關(guān)鍵基因。結(jié)論:LncRNAs在實(shí)驗(yàn)性關(guān)節(jié)炎發(fā)病過(guò)程中具有重要的調(diào)節(jié)作用,LncRNA S56464.1,Lnc RNA XR_006437.1和Lnc RNA J01878可作為其潛在的診斷生物標(biāo)志物和治療靶點(diǎn)。第三部分Lnc RNA S56464.1靶向mi R-152/Wnt通路誘導(dǎo)FLS增殖及黃芪總皂苷干預(yù)作用目的:明確Lnc RNA S56464.1通過(guò)靶向mi R-152/Wnt通路誘導(dǎo)滑膜細(xì)胞的增殖作用,探討黃芪總皂苷治療實(shí)驗(yàn)性關(guān)節(jié)炎的可能機(jī)制。方法:組織塊移植法分離、培養(yǎng)AA大鼠滑膜細(xì)胞,給予LncRNA S56464.1 siRNA和/或黃芪總皂苷干預(yù),MTT法檢測(cè)成纖維樣滑膜細(xì)胞(fibroblast-like synoviocyte,FLS)的增殖反應(yīng);RT-q PCR技術(shù)檢測(cè)Lnc RNA S56464.1干擾和/或AST作用下Lnc RNA S56464.1、mi R-152、β-連環(huán)蛋白(β-catenin)、原癌基因C-myc、細(xì)胞周期蛋白(Cyclin)D1、糖原合成激酶(GSK)-3β和分泌型卷曲相關(guān)蛋白(SFRP)4 m RNA表達(dá)變化;免疫熒光和Western Blot技術(shù)檢測(cè)β-catenin、C-myc、Cyclin D1、GSK-3β、p-GSK-3β(Ser9)和SFRP4蛋白表達(dá)變化。結(jié)果:與模型組相比,Lnc RNA S6464.1干擾組和/或黃芪總皂苷組,不僅可明顯抑制AA大鼠成纖維樣滑膜細(xì)胞的增殖反應(yīng),還可顯著降低Lnc RNA56464.1、β-catenin、C-myc、Cyclin D1 m RNA,明顯抑制β-catenin、C-myc、Cyclin D1和p-GSK-3β(Ser9)/GSK-3β蛋白表達(dá)水平,升高mi R-152和SFRP4 m RNA和/或蛋白表達(dá)水平。結(jié)論:黃芪總皂苷對(duì)實(shí)驗(yàn)性關(guān)節(jié)炎具有一定的治療作用,其機(jī)制可能與下調(diào)Lnc RNA S56464.1表達(dá),調(diào)控mi R-152/Wnt信號(hào)通路,抑制成纖維樣滑膜細(xì)胞增殖有關(guān)。
[Abstract]:Rheumatoid arthritis (RA) is a systemic, autoimmune disease, with chronic inflammation, dysplasia of synovial cells, joint swelling and pressure pain as its clinical features, which can lead to limited joint function, loss of working ability and a heavy burden on patients and society with.RA in 35~50 years of age, and the incidence of women is about approximately Male 2~3 times. At present, the specific pathogenesis of RA is not clear. It is believed that it may be related to immune factors, environmental factors and heredity. Therefore, it is of great theoretical and practical significance to actively explore the pathogenesis of RA and to find potential diagnostic markers. The previous research on the mechanism of RA should focus on the coding gene. In recent years, more and more studies have been made. The non coded RNAs (non-coding RNAs, NC RNAs), which has long been regarded as "noise" and "dark matter", has a complex biological function of the long chain non coded RNAs in.Nc RNAs (long non-coding RNAs, Lnc) is generated from a non coded sequence in the genome, with a length greater than that of a.Nc RNAs and does not have the ability to translate into protein. It can play an important regulatory role in epigenetic level, transcriptional level, translation level and protein modification, which is closely related to a variety of diseases. However, there is still little knowledge about the regulatory role of Lnc RNAs in the development of RA. At present, the treatment of RA in the clinic of Western medicine is mainly to reduce pain and control the symptoms. The side effect is obvious, the patient is not tolerable or poor compliance, and the remote effect is not ideal. Therefore, more and more attention has been paid to the development of RA drugs from traditional Chinese medicine. Astragalus membranaceus is the leguminous plant of Mongolia Astragalus Astragalus membranaceus (Fisch.) Bge.var.mongolicus (Bge.) Hsiao or membranous membranous Astragalus Astragalus membranaceus (Fisch.) Bge.. The dry root, which has the efficacy of stagnation, Qi Yang, and water elimination, is a common medicine in the clinical practice of traditional Chinese medicine. Astragalosides (AST) is an effective part of Astragalus, which mainly contains Astragalus saponins I~VIII. Modern pharmacological research shows that AST has many pharmacological effects, such as anti-inflammatory, antioxidant, immune regulation, anti aging, and so on. On the basis of the preliminary research of the project group, the following studies are carried out as follows: (1) screening of experimental arthritis related long chain noncoding RNAs and the intervention of Astragalus saponins; (2) screening the key Lnc RNAs in the pathogenesis of experimental arthritis based on the Lnc RNA-mi RNA-m RNA co expression network; (3) Lnc RNA S56464.1 targeting mi R-152/Wnt pathway To induce the proliferation of fibroblast-like synoviocytes (FLS) and the intervention of Astragalus saponins in order to systematically reveal the role of Lnc RNAs in the development of experimental arthritis and the role of the total saponins of Astragalus membranaceus, and to reveal the pathogenesis of experimental arthritis from the point of view of Lnc RNAs, and the mechanism of the pathogenesis of experimental arthritis is revealed. To elucidate the possible mechanism of Astragalus total saponins in the treatment of experimental arthritis. The first part of the experimental arthritis related long chain noncoding RNA and the intervention of Astragalus saponins: to screen the differential expression of long chain non coded RNA (long non-coding RNAs, Lnc RNAs) in the pathogenesis of experimental arthritis and to explore the possibility of experimental arthritis. The pathogenesis and the possible target of Astragalus saponins. Methods: the expression of Lnc RNAs/m RNAs in the synovial tissue of adjuvant arthritis (adjuvant arthritis, AA) rats was detected by Lnc RNA gene chip, and the Fold change value was 1.5, and the differential expression basis was screened by P-value0.05, and the gene ontology (Gene) and signal transduction were carried out. Lnc RNA-m RNA co expression network was constructed by Pathway analysis, and the key difference Lnc RNAs was screened and the real-time fluorescent quantitative PCR technique was used to verify it. Results: 260 differentially expressed LncRNAs were screened in the normal group and the model group, of which the Lnc RNAs expression data of the model group were 170, and the Lnc RNAs expression was downregulated. The data were 90, and 675 differentially expressed m RNAs were obtained. In the model group, 422 m RNAs expression data were up-regulated and 253 of M RNAs expression profiles were downregulated; 4163 GO entries were obtained. Among them, the difference genes were enriched in 2494 GO entries and 1669 GO items were enriched with the difference genes, and 42 signal pathways related to differential genes were obtained. The up-regulated genes were enriched in 25 signal pathways, and the differentially regulated genes were enriched in 17 signal pathways. The real-time quantitative PCR detection results of 6 key Lnc RNAs (XR_008357, U75927, MRAK046251, XR_006457, DQ266363 and MRAK003448) were consistent with the results of the gene chip. The normal group, the model group and the AST group screened 75 differential expressions of Lnc RNAs, compared with the normal group and the AST group, the model group up-regulated the Lnc RNAs expression data 41, downregulated the Lnc RNAs expression data, selected 247 differentially expressed m RNAs, the model group raised the m RNAs expression data 171, down the m RNAs expression data 76, and obtained 135 entries, among which 117 items were enriched by 117 entries. The differentially regulated genes were enriched in 18 GO items, and 17 signal pathways related to differential genes were obtained, in which the difference genes were enriched in 14 signal pathways and the differential genes were enriched in 3 signal pathways; the 4 key Lnc RNAs (MRAK012530, MRAK132628, MRAK003448, XR_00645) real-time fluorescent quantitative PCR detection results and gene chips The results are consistent. Conclusion: there is a differential expression of LncRNAs in the pathogenesis of experimental arthritis. The mechanism of AST for the prevention and control of experimental arthritis may be related to the differential expression of Lnc RNAs. The second part is based on the Lnc RNA-mi RNA-m RNA co expression network to screen the key Lnc RNAs in the process of experimental pathogenesis: screening experimental arthritis. The key Lnc RNAs in the pathogenesis was to discuss the possible pathogenesis. Methods: the MI RNAs gene expression profiles were derived from the high throughput gene expression database and published literature in the national biological information center of the United States. The data of Lnc RNAs/m RNAs gene expression profiles were published in the earlier period of the project group, and the standard of differential multiplier 2 and P-value0.05 as the standard Select the differentially expressed Lnc RNAs, MI RNAs and m RNAs, with the help of Miranda and targetscan to predict the m RNAs of differential mi RNAs. On the basis of S, m RNAs and differential mi RNAs, the Lnc RNA-mi RNA-m RNA co expression network is constructed and functional informatics analysis is used to screen the key Lnc RNAs. results in the pathogenesis of experimental arthritis. This network consists of 7 nodes, 24 nodes, 90 nodes, and 301 edges; functional information credits. The results showed that the difference gene was mainly enriched in 147 GO items and 23 signal pathways; LncRNA S56464.1, LncRNA XR_006437.1 and LncRNA J01878 were identified as the key genes in the pathogenesis of experimental arthritis. Conclusion: LncRNAs plays an important role in the pathogenesis of experimental arthritis, LncRNA S56464.1, Lnc RNA. 1 and Lnc RNA J01878 can be used as a potential diagnostic biomarker and therapeutic target. Third part of Lnc RNA S56464.1 target mi R-152/Wnt pathway to induce FLS proliferation and the intervention of Astragalus saponins: Lnc RNA S56464.1 to induce the proliferation of synovial cells by targeting the target pathway, and to explore the treatment experiment of Astragalus saponins The possible mechanism of sexual arthritis. Methods: tissue block transplantation was used to isolate the synovial cells of AA rats and to give the intervention of LncRNA S56464.1 siRNA and / or Astragalus saponins. The proliferation reaction of fibroblast-like synoviocyte (FLS) was detected by MTT, and RT-q PCR technique was used to detect Lnc RNA. 6464.1, MI R-152, beta catenin (beta -catenin), proto oncogene C-myc, cyclin (Cyclin) D1, glycogen synthase kinase (GSK) -3 beta and secretory curl related protein (SFRP) 4 m RNA expression changes. Compared with the model group, the Lnc RNA S6464.1 interference group and / or the total saponins of Astragalus membranaceus can not only significantly inhibit the proliferation of fibroblast like synovial cells in AA rats, but also significantly reduce the Lnc RNA56464.1, beta -catenin, C-myc, Cyclin D1 m RNA, and obviously inhibit the beta protein expression level and increase the level of beta protein. 52 and SFRP4 m RNA and / or protein expression level. Conclusion: the total saponins of Astragalus membranaceus have a certain therapeutic effect on experimental arthritis. The mechanism may be related to the regulation of the expression of Lnc RNA S56464.1, the regulation of MI R-152/Wnt signaling pathway and the inhibition of the proliferation of fibroid synovial cells.
【學(xué)位授予單位】：安徽醫(yī)科大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2017
【分類號(hào)】：R593.22

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2 于�，�;肖秋生;洪建飛;王艷萍;陳正愛;劉瑩;王賀雷;郭玉香;;黃芪有效部位不同提取分離方法的比較[J];藥學(xué)實(shí)踐雜志;2008年01期

3 錢琳;鄧楠;;黃芪提取工藝研究[J];中國(guó)現(xiàn)代醫(yī)學(xué)雜志;2009年11期

4 賀一新;高艷;吳曉俊;王崢濤;;黃芪皂苷對(duì)實(shí)驗(yàn)性自身免疫性腦脊髓炎小鼠的干預(yù)作用[J];中國(guó)藥理學(xué)與毒理學(xué)雜志;2012年03期

5 張軍武;趙琦;王昌利;;正交試驗(yàn)法優(yōu)選黃芪總皂苷醇提工藝[J];河南中醫(yī);2012年08期

6 李文龍;瞿海斌;;黃芪提取過(guò)程總皂苷質(zhì)量濃度的在線監(jiān)測(cè)[J];中草藥;2012年08期

7 易炳學(xué);余書琦;張金蓮;李志強(qiáng);龔千鋒;;黃芪的研究概況[J];江西中醫(yī)藥大學(xué)學(xué)報(bào);2014年02期

8 段振離;;黃芪新功用——防癌[J];家庭中醫(yī)藥;2006年03期

9 唐春榮,張謹(jǐn)福,張秀云,宋強(qiáng),時(shí)曉州;黃芪藥理與治療研究進(jìn)展[J];基層中藥雜志;2002年03期

10 郁帥陸;何旬;陸利霞;熊曉輝;;黃芪固態(tài)發(fā)酵中有效成分的變化[J];食品與藥品;2007年03期

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1 賀一新;高艷;吳曉俊;王崢濤;;黃芪皂苷對(duì)實(shí)驗(yàn)性自身免疫性腦脊髓炎小鼠的干預(yù)作用[A];第十五屆中國(guó)神經(jīng)精神藥理學(xué)學(xué)術(shù)會(huì)議論文摘要[C];2012年

2 付娟;楊世海;黃林芳;陳士林;;黃芪質(zhì)量評(píng)價(jià)研究進(jìn)展[A];第十一屆全國(guó)青年藥學(xué)工作者最新科研成果交流會(huì)論文集[C];2012年

3 邱新茹;;黃芪的臨床應(yīng)用概況[A];中華中醫(yī)藥學(xué)會(huì)中醫(yī)、中西醫(yī)結(jié)合治療常見病研討會(huì)論文集[C];2007年

4 王海霞;羅耀群;;中醫(yī)理論與現(xiàn)代藥理學(xué)中的黃芪藥理作用研究進(jìn)展[A];2013年中國(guó)藥學(xué)大會(huì)暨第十三屆中國(guó)藥師周論文集[C];2013年

5 金由辛;;面向21世紀(jì)的RNA研究[A];面向21世紀(jì)的科技進(jìn)步與社會(huì)經(jīng)濟(jì)發(fā)展（下冊(cè)）[C];1999年

6 ;第四屆RNA全國(guó)研討會(huì)大會(huì)報(bào)告日程安排[A];第四屆全國(guó)RNA進(jìn)展研討會(huì)論文集[C];2005年

7 ;Function of Transfer RNA Modifications in Plant Development[A];植物分子生物學(xué)與現(xiàn)代農(nóng)業(yè)——全國(guó)植物生物學(xué)研討會(huì)論文摘要集[C];2010年

8 王峰;張秋平;陳金湘;;棉花總RNA的快速提取方法[A];中國(guó)棉花學(xué)會(huì)2011年年會(huì)論文匯編[C];2011年

9 關(guān)力;陳本iY;iJ云虹;郭培芝;魏重琴;邱蘇吾;苗健;;關(guān)于動(dòng)物}D~T中RNAn,定方法的研究[A];中國(guó)生理科學(xué)會(huì)學(xué)術(shù)會(huì)議論文摘要匯編（生物化學(xué)）[C];1964年

10 夏海濱;;小RNA在免疫學(xué)領(lǐng)域中的應(yīng)用研究進(jìn)展[A];中國(guó)免疫學(xué)會(huì)第五屆全國(guó)代表大會(huì)暨學(xué)術(shù)會(huì)議論文摘要[C];2006年

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1 陳治奎;黃芪長(zhǎng)期給藥降壓效果好[N];中國(guó)醫(yī)藥報(bào);2004年

2 張曉丹；佟欣；劉琳；朱英淑;黨參與黃芪抗心肌缺血各有千秋[N];中國(guó)醫(yī)藥報(bào);2004年

3 張中橋;黃芪丹參復(fù)方制劑對(duì)心肌細(xì)胞起保護(hù)作用[N];中國(guó)醫(yī)藥報(bào);2006年

4 記者 馮衛(wèi)東;研究人員發(fā)現(xiàn)可破壞腫瘤抑制基因的小RNA[N];科技日?qǐng)?bào);2009年

5 記者 儲(chǔ)笑抒 通訊員 盛偉;人體微小RNA有望提前發(fā)出癌癥預(yù)警[N];南京日?qǐng)?bào);2011年

6 瀘州醫(yī)學(xué)院副教授、科普作家 周志遠(yuǎn);“大頭兒子”與環(huán)狀RNA[N];第一財(cái)經(jīng)日?qǐng)?bào);2014年

7 麥迪信;小分子RNA可能有大作用[N];醫(yī)藥經(jīng)濟(jì)報(bào);2003年

8 董映璧;美發(fā)現(xiàn)基因調(diào)控可回應(yīng)“RNA世界”[N];科技日?qǐng)?bào);2006年

9 張忠霞;特制RNA輕推一下,就能“喚醒”基因[N];新華每日電訊;2007年

10 聶翠蓉;RNA：縱是配角也精彩[N];科技日?qǐng)?bào);2009年

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1 姜輝;實(shí)驗(yàn)性關(guān)節(jié)炎相關(guān)長(zhǎng)鏈非編碼RNAs的篩選、功能研究及黃芪總皂苷的干預(yù)作用[D];安徽醫(yī)科大學(xué);2017年

2 劉小花;基于抗胃潰瘍作用的黃芪譜效關(guān)系和相關(guān)成分的體內(nèi)代謝研究[D];蘭州大學(xué);2015年

3 張瑜;淫羊藿、黃芪、葛根有效成分組方對(duì)阿爾茨海默病腦鐵超載的干預(yù)作用及其機(jī)制研究[D];河北醫(yī)科大學(xué);2016年

4 陳云志;基于維生素D系統(tǒng)探討黃芪皂苷抗心肌肥大的分子機(jī)制[D];北京中醫(yī)藥大學(xué);2017年

5 段琦梅;黃芪、黨參質(zhì)量評(píng)價(jià)及其提取物活性研究[D];西北農(nóng)林科技大學(xué);2010年

6 崔寧;基于全基因表達(dá)譜的黃芪及其拆分組分健脾祛濕機(jī)制研究[D];山東中醫(yī)藥大學(xué);2015年

7 蘇敬澤;黃芪組分對(duì)肥厚心肌能量代謝的干預(yù)作用及機(jī)制研究[D];北京中醫(yī)藥大學(xué);2008年

8 王趙瑋;昆蟲RNA病毒復(fù)制及昆蟲抗病毒天然免疫機(jī)制研究[D];武漢大學(xué);2014年

9 包純;一類新非編碼RNA的發(fā)現(xiàn)以及產(chǎn)生和功能的初探[D];華中師范大學(xué);2015年

10 李語(yǔ)麗;基于MeRIP-seq的水稻RNA m6A甲基化修飾的研究[D];中國(guó)科學(xué)院北京基因組研究所;2015年

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1 高彥云;綠葉揮發(fā)物介導(dǎo)黃芪生長(zhǎng)及次生代謝作用研究[D];山西大學(xué);2015年

2 李艷敏;黃芪、葛根組分配伍對(duì)糖尿病大鼠肝臟糖脂代謝的影響[D];遼寧中醫(yī)藥大學(xué);2015年

3 郝明芬;黃芪葛根配伍對(duì)糖尿病大鼠胰腺糖脂代謝的影響及交互效應(yīng)[D];遼寧中醫(yī)藥大學(xué);2016年

4 楊楠;基于胞內(nèi)蛋白/膜蛋白結(jié)合特性的金復(fù)康優(yōu)化方防治肺癌物質(zhì)基礎(chǔ)研究：黃芪相關(guān)的組分結(jié)構(gòu)特征及其生物藥劑學(xué)性質(zhì)[D];南京中醫(yī)藥大學(xué);2017年

5 閆明明;黃芪中黃芪皂苷成分的提取分離與純化工藝研究[D];東北林業(yè)大學(xué);2010年

6 許平平;真菌微生物酶轉(zhuǎn)化黃芪皂苷的研究[D];大連工業(yè)大學(xué);2009年

7 張金紅;提高黃芪中有效成分的提取方法研究[D];天津醫(yī)科大學(xué);2010年

8 賈剛;黃芪有效組分的提取分離及結(jié)構(gòu)鑒定[D];長(zhǎng)春中醫(yī)藥大學(xué);2008年

9 趙向國(guó);人參、黃芪炮制前后化學(xué)成分及活性研究[D];長(zhǎng)春中醫(yī)藥大學(xué);2012年

10 張潮林;保留灌腸劑—復(fù)方黃芪腸寧顆粒的藥學(xué)部分研究[D];廣東藥學(xué)院;2008年

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