本文選題：DNA甲基化轉(zhuǎn)移酶1 + 激活素A��； 參考：《吉林大學(xué)》2017年博士論文

【摘要】：研究背景激活素A屬于TGF-β超家族成員,其受體屬于絲氨酸/蘇氨酸激酶(Ser/Thr)型受體,分為I型受體及II型受體,激活素與II型結(jié)合,再招募I型受體,進(jìn)而通過細(xì)胞內(nèi)Smads信號(hào)蛋白,或非Smads依賴的MAPK通路、Rho GTPase通路和PI3K/Akt通路傳導(dǎo)信號(hào)至細(xì)胞核,激活靶基因轉(zhuǎn)錄。有關(guān)研究顯示,激活素A的表達(dá)與腫瘤的發(fā)生發(fā)展密切相關(guān),參與多種腫瘤細(xì)胞增殖及凋亡調(diào)控。如大腸癌及骨肉瘤等患者外周血激活素A水平升高,大腸癌及卵巢癌等組織高表達(dá)激活素A,激活素A可以誘導(dǎo)肺腺癌細(xì)胞凋亡、促進(jìn)前列腺癌細(xì)胞轉(zhuǎn)移,激活素A表達(dá)異常還與腫瘤惡液質(zhì)形成有關(guān)等。DNA甲基化是由DNA甲基化轉(zhuǎn)移酶DNMTs(DNA methyltransferases,Dnmts)催化并維持的,DNMTs家族包括DNMT1、DNMT2、DNMT3a、DNMT3b及DNMT3L。DNMTs是調(diào)控表觀遺傳學(xué)DNA甲基化的重要分子,DNMT1主要起維持性甲基化酶作用。以往的研究顯示,DNMTs在腫瘤細(xì)胞中高表達(dá),DNMTs的表達(dá)還能影響胚胎發(fā)育過程,推測(cè)細(xì)胞核潛能越高與DNMTs的調(diào)控關(guān)系越密切。激活素也具有調(diào)控中胚層細(xì)胞發(fā)育及腫瘤細(xì)胞增殖的作用,但是,激活素A能否通過調(diào)控DNMTs表達(dá),影響腫瘤細(xì)胞增殖及凋亡,仍不清楚。因此,本研究通過預(yù)實(shí)驗(yàn),選擇對(duì)激活素A敏感的小鼠骨髓瘤細(xì)胞系NS-1細(xì)胞作為靶細(xì)胞,探討激活素A調(diào)控NS-1細(xì)胞增殖及凋亡與DNMT1表達(dá)的關(guān)系。課題分為四方面進(jìn)行論述,第一部分分析了激活素A對(duì)多種腫瘤細(xì)胞的生物學(xué)作用,探討激活素A作用與DNMT1關(guān)系。第二部分闡述了激活素A調(diào)控小鼠骨髓瘤細(xì)胞NS-1增殖及凋亡作用及其信號(hào)機(jī)制,分析激活素信號(hào)蛋白Smad3 Knock-down及過表達(dá)對(duì)DNMT1的影響。第三部分通過DNMT1Knock-down,進(jìn)一步探討改變DNMT1表達(dá)對(duì)激活素A抑制NS-1細(xì)胞增殖及誘導(dǎo)凋亡的影響及其機(jī)制。第四部分建立NS-1荷瘤鼠模型,評(píng)價(jià)激活素A及DNMT1 Knock-down對(duì)小鼠體內(nèi)NS-1細(xì)胞成瘤的影響。研究方法RT-PCR及Western blotting檢測(cè)DNMT1在NS-1細(xì)胞的表達(dá)。MTT法、CFSE染色、Hochest33342染色及Annexin V-7AAD評(píng)價(jià)NS-1腫瘤細(xì)胞活力及凋亡。構(gòu)建pLVX-U6/Puro-DNMT1 sh RNA表達(dá)質(zhì)粒,轉(zhuǎn)染NS-1細(xì)胞評(píng)價(jià)敲低DNMT1基因?qū)?xì)胞增殖及凋亡的影響。建立NS-1細(xì)胞荷瘤鼠模型,HE染色、免疫組織化學(xué)染色、Tunel法評(píng)價(jià)DNMT1基因Knock-down對(duì)NS-1細(xì)胞成瘤的影響。研究結(jié)果第一部分激活素A對(duì)多種腫瘤細(xì)胞活性及DNMT1表達(dá)的影響DNMT1在腫瘤細(xì)胞高表達(dá),而在正常組織來源細(xì)胞低表達(dá)。Giemsa染色法顯示激活素A作用于SW480、Hela、A549、NS-1細(xì)胞后發(fā)生明顯的細(xì)胞形態(tài)學(xué)改變,提示激活素A可以影響NS-1細(xì)胞形態(tài)變化。且在低濃度5ng/ml時(shí)激活素A即可影響NS-1細(xì)胞形態(tài)變化。同時(shí)可見激活素A可以顯著抑制骨髓瘤細(xì)胞系NS-1細(xì)胞DNMT1表達(dá)。因此,實(shí)驗(yàn)采用NS-1細(xì)胞作為激活素A敏感細(xì)胞,進(jìn)行后續(xù)研究。第二部分激活素A誘導(dǎo)小鼠骨髓瘤細(xì)胞系NS-1凋亡為了確定激活素A對(duì)NS-1細(xì)胞的作用,實(shí)驗(yàn)首先采用MTT法檢測(cè)NS-1細(xì)胞活力,結(jié)果顯示激活素A可以抑制NS-1細(xì)胞活力。CFSE染色進(jìn)一步顯示,激活素A抑制了NS-1細(xì)胞增殖。Hocheast染色和Annexin V-7AAD結(jié)果顯示激活素A可以促進(jìn)NS-1細(xì)胞凋亡。Western blotting結(jié)果顯示激活素A上調(diào)NS-1細(xì)胞Bax、Cyc C及Caspase3表達(dá),而抑制Bcl2及DNMT1表達(dá),提示激活素A通過線粒體凋亡途徑誘導(dǎo)NS-1細(xì)胞凋亡,其作用可能與下調(diào)DNMT1表達(dá)有關(guān)。進(jìn)一步研究顯示,激活素A可以促進(jìn)NS-1細(xì)胞表達(dá)激活素信號(hào)蛋白Smad3,但過表達(dá)和Knock-down Smad3不能影響NS-1細(xì)胞DNMT1表達(dá),提示激活素A可能通過Smad3信號(hào)非依賴途徑調(diào)控DNMT1表達(dá)。第三部分DNMT1 Knock-down對(duì)NS-1細(xì)胞的活力及凋亡的影響Western blotting結(jié)果顯示構(gòu)建的pLVX-DNMT1干涉質(zhì)粒轉(zhuǎn)染NS-1細(xì)胞成功敲低了DNMT1表達(dá),同時(shí)上調(diào)NS-1細(xì)胞Cyc C及Caspase3表達(dá)及Bax/Bcl2比值。MTT結(jié)果顯示NS-1細(xì)胞轉(zhuǎn)染0.5μg pLVX-DNMT1質(zhì)粒24h后,與pLVX對(duì)照組質(zhì)粒轉(zhuǎn)染NS-1細(xì)胞組比較細(xì)胞活力明顯下降;添加5ng/ml激活素A組,較激活素A處理的pLVX對(duì)照組質(zhì)粒轉(zhuǎn)染NS-1細(xì)胞組細(xì)胞活力進(jìn)一步下降。Annexin V-7AAD結(jié)果顯示轉(zhuǎn)染pLVX-DNMT1質(zhì)粒可以誘導(dǎo)NS-1細(xì)胞發(fā)生凋亡。第四部分DNMT1 Knock-down對(duì)小鼠NS-1細(xì)胞成瘤的影響為了進(jìn)一步確定DNMT1 Knock-down對(duì)激活素A誘導(dǎo)NS-1細(xì)胞凋亡的影響,實(shí)驗(yàn)首先采用不同濃度的NS-1細(xì)胞接種Balb/c小鼠背部,觀察成瘤情況。結(jié)果顯示2.0x106 NS-1細(xì)胞/0.1ml接種小鼠背部皮下,成功構(gòu)建了NS-1細(xì)胞荷瘤鼠模型。進(jìn)一步分析DNMT1 Knock-down對(duì)小鼠NS-1細(xì)胞體內(nèi)成瘤影響。實(shí)驗(yàn)采用預(yù)轉(zhuǎn)染pLVX-NC空質(zhì)粒、轉(zhuǎn)染pLVX-DNMT1 sh RNA表達(dá)質(zhì)粒及未轉(zhuǎn)染質(zhì)粒的野生型NS-1接種Balb/c小鼠背部,體內(nèi)測(cè)量腫瘤體積結(jié)果顯示,與pLVX-NC組相比,pLVX-DNMT1組的NS-1細(xì)胞成瘤能力明顯減弱,且體積增長(zhǎng)減慢。提示DNMT1 Knock-down可以抑制NS-1細(xì)胞體內(nèi)成瘤能力。待腫瘤生長(zhǎng)到第18天處死Balb/c小鼠取腫瘤,結(jié)果顯示與pLVX-NC組相比,pLVX-DNMT1組的NS-1細(xì)胞腫瘤體積明顯降低,具有統(tǒng)計(jì)學(xué)差異。提取腫瘤組織總蛋白Westernblotting結(jié)果顯示pLVX-DNMT1組成功敲底了DNMT1的表達(dá),且HE染色結(jié)果和免疫組織化學(xué)染色結(jié)果顯示與pLVX-NC組相比,pLVX-DNMT1組細(xì)胞核漿比例明顯增加、排列紊亂、局部出現(xiàn)膿腫和壞死,提示DNMT1 Knock-down可以誘導(dǎo)NS-1細(xì)胞瘤發(fā)生凋亡,可能具有骨髓瘤治療價(jià)值。Tunnel染色顯示與激活素A處理的pLVX-NC組相比,激活素A處理的DNMT1 Knock-down的NS-1細(xì)胞腫瘤組織存在更多的染色陽性細(xì)胞,提示DNMT1 Knock-down促進(jìn)了激活素A誘導(dǎo)NS-1細(xì)胞凋亡作用。綜上所述,DNMT1是DNA甲基化表觀遺傳學(xué)調(diào)控的重要分子蛋白,降低NS-1細(xì)胞DNMT1的表達(dá)水平,可以通過線粒體凋亡途徑抑制NS-1細(xì)胞增殖、促進(jìn)NS-1細(xì)胞凋亡。激活素A可以調(diào)控腫瘤細(xì)胞DNMT1表達(dá),對(duì)治療DNA甲基化修飾異常所引發(fā)的腫瘤疾病具有重要的意義。
[Abstract]:Background activin A belongs to the member of the TGF- beta superfamily, whose receptor belongs to the serine / threonine kinase (Ser/Thr) receptor, which is divided into I type and II receptor. Activin is combined with II type, and then recruitment of I type receptor, and then through intracellular Smads signal protein, or MAPK pathway of non Smads dependent Lai, Rho GTPase pathway and transduction pathway. The study shows that the expression of activin A is closely related to the occurrence and development of tumor, and participates in the regulation of proliferation and apoptosis of various tumor cells. The levels of peripheral blood activin A in patients with colorectal cancer and osteosarcoma, such as large intestine and ovarian cancer, are high expression of activin A, and activin A can induce lung gland. The apoptosis of cancer cells, the promotion of the metastasis of prostate cancer cells, the abnormal expression of activin A and the formation of.DNA methylation related to the formation of malignant tumor fluid are catalyzed and maintained by DNA methyltransferase DNMTs (DNA methyltransferases, Dnmts). The DNMTs family consists of DNMT1, DNMT2, DNMT3a, DNMT3b, and regulating the weight of epigenetic methylation. DNMT1 mainly acts as a maintainable methylation enzyme. Previous studies have shown that DNMTs is highly expressed in tumor cells, and the expression of DNMTs can also affect the process of embryonic development. It is presumed that the higher the cell nuclear potential is, the closer the relationship between the regulation of DNMTs and the regulation of mesoderm cell development and tumor cell proliferation. Whether or not A can affect the proliferation and apoptosis of tumor cells by regulating the expression of DNMTs and affecting the proliferation and apoptosis of tumor cells is still unclear. Therefore, this study selects the NS-1 cell line of murine myeloma cell line sensitive to activin A as a target cell, and discusses the relationship between activin A regulation of NS-1 cell proliferation and apoptosis and the expression of DNMT1. The subject is divided into four aspects. The first part analyses the biological effect of activin A on a variety of tumor cells, and discusses the relationship between activin A and DNMT1. Second the effect of activin A on the proliferation and apoptosis of murine myeloma cells and its signal mechanism and the effect of Smad3 Knock-down on activin signal protein and the effect of overexpression on DNMT1 are discussed. The third part is connected with the activity of activin protein. DNMT1Knock-down, further explore the effect and mechanism of DNMT1 expression on activin A inhibition of NS-1 cell proliferation and induction of apoptosis. Fourth the model of NS-1 bearing mice was established to evaluate the effect of activin A and DNMT1 Knock-down on the tumor formation of NS-1 cells in mice. The expression of.MTT, CFSE staining, Hochest33342 staining and Annexin V-7AAD were used to evaluate the viability and apoptosis of NS-1 tumor cells. PLVX-U6/Puro-DNMT1 sh RNA expression plasmid was constructed, and NS-1 cells were transfected to evaluate the effect of low DNMT1 gene on cell proliferation and apoptosis. The effect of NMT1 gene Knock-down on the tumor formation of NS-1 cells. The first part of the study was the effect of activin A on the activity of various tumor cells and the expression of DNMT1, DNMT1 was highly expressed in the tumor cells, and the expression of activin A in the normal tissue derived cells showed that the activin A acted upon SW480, Hela, A549, and NS-1 cells. It is suggested that activin A can affect the morphological changes of NS-1 cells, and activin A can affect the morphological changes of NS-1 cells at low concentration of 5ng/ml. At the same time, activin A can significantly inhibit the expression of DNMT1 in myeloma cell line NS-1 cells. Therefore, the experiment uses NS-1 cells as activin A sensitive cells for follow-up study. Second parts Activin A induced the apoptosis of mouse myeloma cell line NS-1 in order to determine the effect of activin A on NS-1 cells. First, the MTT assay was used to detect the activity of NS-1 cells. The results showed that activin A can inhibit the.CFSE staining of NS-1 cell viability further. Activin A inhibits NS-1 cell proliferation.Hocheast staining and the result of NS-1. Activin A can promote NS-1 cell apoptosis,.Western blotting results show that activin A up-regulated NS-1 cells Bax, Cyc C and Caspase3 expression, and inhibits Bcl2 and DNMT1 expression, suggesting that activin may induce apoptosis through mitochondrial apoptosis pathway, and its role may be related to down regulation. The expression of activin signal protein Smad3 was expressed in NS-1 cells, but overexpression and Knock-down Smad3 did not affect the DNMT1 expression in NS-1 cells, suggesting that activin A may regulate DNMT1 expression through non dependent pathway of Smad3 signal. Third part DNMT1 Knock-down on the vitality and apoptosis of NS-1 cells The transfection of NS-1 cells with the interference plasmid successfully knocked down the expression of DNMT1, at the same time, the expression of Cyc C and Caspase3 in NS-1 cells and the Bax/Bcl2 ratio.MTT results showed that the NS-1 cells transfected to 0.5 mu g pLVX-DNMT1 plasmid 24h, compared with the control group plasmids transfected to the cell group, the cell viability was significantly decreased. LVX control group plasmid transfected NS-1 cell cell viability further decreased.Annexin V-7AAD results showed that transfection of pLVX-DNMT1 plasmids could induce apoptosis of NS-1 cells. Fourth the effect of DNMT1 Knock-down on the tumor formation of mice NS-1 cells in order to further determine the effect of DNMT1 Knock-down on the apoptosis of activin A induced cells. First of all, NS-1 cells with different concentrations were inoculated on the back of Balb/c mice to observe the tumor formation. The results showed that the 2.0x106 NS-1 cell /0.1ml was inoculated subcutaneously on the back of the mouse, and the tumor mouse model of NS-1 cells was successfully constructed. The effect of DNMT1 Knock-down on the tumor formation in the mice NS-1 cells was further analyzed. The experiment was carried out by pre transfection of pLVX-NC empty plasmid and transfection pLV. X-DNMT1 sh RNA expression plasmid and untransfected wild type NS-1 were inoculated on the back of Balb/c mice. The volume of tumor volume measured in vivo showed that the tumor formation ability of NS-1 cells in pLVX-DNMT1 group decreased significantly and slowed down compared with pLVX-NC group, suggesting that DNMT1 Knock-down could inhibit the tumorigenesis of NS-1 cells. 18 days after the death of Balb/c mice, the results showed that the volume of NS-1 cells in the group pLVX-DNMT1 was significantly lower than that in the pLVX-NC group, with a statistically significant difference. The result of the extraction of the total protein of the tumor tissue Westernblotting showed that the pLVX-DNMT1 group successfully knocked down the expression of DNMT1, and the results of HE staining and immunohistochemical staining showed pLVX-. Compared with group NC, the proportion of cell nuclear plasma in pLVX-DNMT1 group was obviously increased, arranged in disorder, local abscess and necrosis, suggesting that DNMT1 Knock-down could induce apoptosis of NS-1 cytoma, which might have the value of myeloma treatment with.Tunnel staining, compared with pLVX-NC group treated with activin A, DNMT1 Knock-down NS-1 cell swelling of activin A treatment. More staining positive cells exist in the tumor tissue, suggesting that DNMT1 Knock-down promotes the apoptosis of NS-1 cells induced by activin A. To sum up, DNMT1 is an important molecular protein of DNA methylation epigenetic regulation, which reduces the expression level of DNMT1 in NS-1 cells, and can inhibit the proliferation of NS-1 cells through mitochondrial apoptosis pathway and promote NS-1 cells. Apoptosis, activin A can regulate the expression of DNMT1 in tumor cells, which is of great significance in the treatment of tumor diseases caused by abnormal DNA methylation.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2017
【分類號(hào)】：R730.2

【相似文獻(xiàn)】

相關(guān)期刊論文 前10條

1 周璐,李定國;激活素A與肝臟[J];中華消化雜志;2001年12期

2 楊軍;張峰;;激活素A的基礎(chǔ)及臨床研究[J];黑龍江醫(yī)藥科學(xué);2009年06期

3 董輝,黃志紅,楊煜,柳忠輝;不同年齡段健康成年人外周血激活素A水平的變化[J];中國老年學(xué)雜志;2004年12期

4 安麗;王學(xué)燕;烏娟;;激活素對(duì)新生大鼠缺氧缺血性腦損傷后神經(jīng)元的保護(hù)[J];中國臨床康復(fù);2006年12期

5 于f ;王軼楠;楊清;孟小丹;孫洋;臺(tái)桂香;柳忠輝;;激活素A及激活素結(jié)合蛋白在急性酒精性肝損傷小鼠肝組織中的表達(dá)[J];中國生物制品學(xué)雜志;2011年03期

6 張宸豪;李瑤;方芳;李妍;;激活素的生理功能及其臨床意義的研究進(jìn)展[J];吉林醫(yī)藥學(xué)院學(xué)報(bào);2012年03期

7 王世瑤;柳忠輝;牟大鵬;張紅軍;楊瓊;常穎;臺(tái)桂香;;激活素受體相互作用蛋白4的基因克隆[J];吉林大學(xué)學(xué)報(bào)(醫(yī)學(xué)版);2007年01期

8 裴穎;左玲;欒永昕;于維芹;蘇冠方;;激活素A對(duì)人皮膚微血管內(nèi)皮細(xì)胞周期的影響[J];中國老年學(xué)雜志;2009年05期

9 胡德恩;;調(diào)節(jié)細(xì)胞激活素在抗癌治療中的意義[J];國外醫(yī)學(xué)(腫瘤學(xué)分冊(cè));1992年05期

10 于曉明;友情是健康的激活素[J];中國保健營(yíng)養(yǎng);1997年10期

相關(guān)會(huì)議論文 前10條

1 劉海巖;臺(tái)桂香;崔雪玲;陳芳芳;葛敬巖;柳忠輝;;激活素受體相互作用蛋白1，2在小鼠組織中的表達(dá)及其功能研究[A];第六屆全國免疫學(xué)學(xué)術(shù)大會(huì)論文集[C];2008年

2 葛偉;;激活素在魚類繁殖和發(fā)育中的調(diào)控作用[A];生命科學(xué)與生物技術(shù)：中國科協(xié)第三屆青年學(xué)術(shù)年會(huì)論文集[C];1998年

3 柳忠輝;張學(xué)軍;勞鳳學(xué);李一;;激活素受體相互作用蛋白3的基因克隆和鑒定[A];中國免疫學(xué)會(huì)第四屆學(xué)術(shù)大會(huì)會(huì)議議程及論文摘要集[C];2002年

4 張學(xué)軍;;巨噬細(xì)胞一氧化氮檢測(cè)及激活素對(duì)——氧化氮產(chǎn)生的調(diào)節(jié)機(jī)制[A];第五次全國中青年檢驗(yàn)醫(yī)學(xué)學(xué)術(shù)會(huì)議論文匯編[C];2006年

5 于玲;李俊;孔剛;李玉俠;尚濤;王雁玲;;激活素A對(duì)滋養(yǎng)層細(xì)胞浸潤(rùn)和凋亡的雙相作用[A];第一屆中華醫(yī)學(xué)會(huì)生殖醫(yī)學(xué)分會(huì)、中國動(dòng)物學(xué)會(huì)生殖生物學(xué)分會(huì)聯(lián)合年會(huì)論文匯編[C];2007年

6 袁發(fā)煥;李芙蓉;;激活素A及卵泡抑素對(duì)大鼠腎間質(zhì)成纖維細(xì)胞的影響[A];中華醫(yī)學(xué)會(huì)腎臟病學(xué)分會(huì)2006年學(xué)術(shù)年會(huì)論文集[C];2006年

7 宋綺穎;沈宗姬;;抑制素A和激活素A與胎兒生長(zhǎng)受限關(guān)系的研究[A];2011中國婦產(chǎn)科學(xué)術(shù)會(huì)議暨浙江省計(jì)劃生育與生殖醫(yī)學(xué)學(xué)術(shù)年會(huì)暨生殖健康講習(xí)班論文匯編[C];2011年

8 張學(xué)軍;姚智;;IL-1β在巨噬細(xì)胞中的檢測(cè)及激活素A對(duì)其活性的調(diào)節(jié)[A];第四屆全國臨床檢驗(yàn)學(xué)術(shù)會(huì)議論文匯編[C];2006年

9 柳忠輝;張鵬宇;張紅軍;張學(xué)軍;王世瑤;臺(tái)桂香;;ActRIPs介導(dǎo)的激活素調(diào)控小鼠巨噬細(xì)胞活性的信號(hào)傳導(dǎo)機(jī)制研究[A];中國免疫學(xué)會(huì)第五屆全國代表大會(huì)暨學(xué)術(shù)會(huì)議論文摘要[C];2006年

10 劉錫梅;尉紅;耿巖;;妊娠中期CRP、激活素A等水平與LBWF關(guān)系的研究[A];中華醫(yī)學(xué)會(huì)第二次全國產(chǎn)科熱點(diǎn)問題研討會(huì)及第一屆全國產(chǎn)科主任論壇學(xué)術(shù)會(huì)議論文匯編[C];2004年

相關(guān)博士學(xué)位論文 前10條

1 吳雙;激活素A在人大腸癌組織中的表達(dá)及其作用研究[D];吉林大學(xué);2016年

2 張?jiān)封?激活素A通過甲基轉(zhuǎn)移酶1誘導(dǎo)骨髓瘤細(xì)胞系NS-1細(xì)胞凋亡[D];吉林大學(xué);2017年

3 李楠;激活素A調(diào)控單核巨噬細(xì)胞活性及其作用機(jī)制[D];吉林大學(xué);2013年

4 張紅軍;激活素受體相互作用蛋白2在小鼠肝細(xì)胞中的表達(dá)及其作用機(jī)制研究[D];吉林大學(xué);2007年

5 霍德勝;激活素A促炎作用研究[D];吉林大學(xué);2009年

6 徐桂月;激活素受體相互作用蛋白3的基因克隆及其特性研究[D];吉林大學(xué);2006年

7 張宸豪;激活素受體相互作用蛋白5基因克隆及其在小鼠胰腺組織中的表達(dá)和作用研究[D];吉林大學(xué);2010年

8 張學(xué)軍;激活素受體相互作用蛋白2在巨噬細(xì)胞中介導(dǎo)激活素信號(hào)傳導(dǎo)機(jī)制的研究[D];吉林大學(xué);2004年

9 李占東;人激活素受體結(jié)合蛋白2的克隆、鑒定及其與乳腺癌相關(guān)性的研究[D];東北師范大學(xué);2009年

10 李俊;激活素A對(duì)人早孕滋養(yǎng)層細(xì)胞凋亡的調(diào)節(jié)及與妊娠期高血壓疾病關(guān)系研究[D];中國醫(yī)科大學(xué);2005年

相關(guān)碩士學(xué)位論文 前10條

1 程序;激活素A的真核表達(dá)以及中藥抗腫瘤激活素A相關(guān)機(jī)制的初步探討[D];東北師范大學(xué);2008年

2 李繼茹;激活素A和脂多糖對(duì)小鼠腹腔巨噬細(xì)胞的活化作用及其機(jī)制研究[D];吉林大學(xué);2013年

3 李楠;激活素A誘導(dǎo)小鼠單核巨噬細(xì)胞分化和成熟的作用研究[D];吉林大學(xué);2010年

4 孔剛;不同濃度激活素A對(duì)細(xì)胞滋養(yǎng)層細(xì)胞行為的影響[D];中國醫(yī)科大學(xué);2006年

5 李海燕;激活素A對(duì)小鼠巨噬細(xì)胞白細(xì)胞介素6表達(dá)調(diào)控的研究[D];吉林大學(xué);2006年

6 徐妍婷;胎盤中激活素受體的表達(dá)及與胎兒生長(zhǎng)受限的關(guān)系[D];蘇州大學(xué);2014年

7 謝姣;激活素A及其信號(hào)蛋白在小鼠肝切除再生中的表達(dá)研究[D];吉林大學(xué);2008年

8 常霞;激活素A對(duì)新生大鼠缺氧缺血性腦損傷后腦組織巢蛋白的影響[D];山西醫(yī)科大學(xué);2010年

9 宋春雷;草魚激活素Ⅰ型和Ⅱ型受體的cDNA克隆、結(jié)構(gòu)分析及其在垂體細(xì)胞中的表達(dá)調(diào)控的研究[D];電子科技大學(xué);2009年

10 常穎;激活素A促進(jìn)人晶狀體上皮細(xì)胞增殖作用的研究[D];吉林大學(xué);2006年

，

本文編號(hào)：2098495