本文選題：顆粒細胞 + 凋亡��； 參考：《南方醫(yī)科大學(xué)》2007年博士論文

【摘要】： 卵細胞和胚胎的衰老和死亡是制約體外受精-胚胎移植(in vitro fertilization embryo transfer，IVF-ET)等輔助生殖技術(shù)(assisted reproduetive techniques，ART)成功率提高的一個關(guān)鍵因素。而細胞凋亡是卵細胞和胚胎死亡的主要方式，也是導(dǎo)致卵細胞受精障礙和胚胎發(fā)育停滯、著床失敗的主要原因。可以設(shè)想，若能抑制卵細胞和胚胎的凋亡，將顯著提高胚胎的質(zhì)量及輔助生殖的成功率。導(dǎo)致細胞凋亡的原因很多，抗凋亡分子和促凋亡分子在調(diào)節(jié)卵細胞和胚胎細胞凋亡方面起著極為重要的作用，它們之間的平衡決定著細胞的存活和死亡。其中，Bcl-2家族起著重要的作用，Bax、Bak是其亞家族中的成員，具有促凋亡作用。本研究從一個全新的角度，首次提出通過抗凋亡人工干預(yù)的方法來促進胚胎發(fā)育。我們以人顆粒細胞和小鼠早期胚胎為研究對象，采用基因轉(zhuǎn)染法，在人顆粒細胞和小鼠胚胎內(nèi)轉(zhuǎn)入Bax、Bak等凋亡分子的小分子干擾RNA(small interfering RNA，siRNA)，通過干擾Bax等凋亡分子mRNA表達從而提升Bcl-2等抗凋亡分子的含量比例等方法分析體外人工抗凋亡干預(yù)措施對早期胚胎發(fā)育的影響，尋找一條提高卵子和胚胎質(zhì)量的新途徑，也為提高胚胎干細胞培養(yǎng)中的囊胚形成率奠定一定的基礎(chǔ)，從而為最終將抗凋亡干預(yù)應(yīng)用于臨床不孕癥輔助治療提供理論和實驗依據(jù)。 第一部分干擾Bax-Bak基因表達 目的 通過轉(zhuǎn)染Bax、Bak小分子干擾RNA(siRNA)，，干擾Bax、Bak等凋亡分子的功能，研究其對人顆粒細胞凋亡的影響，為提高卵子、胚胎質(zhì)量提供新的思路及理論依據(jù)。 方法 1、用Westernblot檢測Bax、Bak-siRNA； 2、將Bax、Bak-siRNA分別或同時轉(zhuǎn)染入人顆粒細胞，觀察基本形態(tài)，用流式細胞儀檢測顆粒細胞的凋亡。 3、實驗設(shè)置空白對照組、陽性對照組、陰性對照組、Bax干擾組、Bak干擾組、gax-Bak干擾組。 結(jié)果 1、esternblot檢測： 轉(zhuǎn)染了Bax-siRNA和Bak-siRNA后的條帶減弱，說明細胞內(nèi)Bax、Bak含量降低。 2、基本形態(tài)觀察： 1)空白對照組、Bak干擾組、Bak+Bax干擾組細胞形態(tài)正常，多為多邊形和梭形，以貼壁為主。 2)Bax干擾組細胞形態(tài)基本正常，胞質(zhì)中有少數(shù)黑點，多為多邊形和梭形，以貼壁為主。 3)陽性對照組、陰性對照組細胞變圓，收縮，細胞間距大，胞質(zhì)中有較多黑點。 3、流式細胞儀檢測結(jié)果： 1)Bak干擾組的凋亡指數(shù)為3.44％，BaxBak聯(lián)合干擾組的凋亡指數(shù)為3.97％，明顯低于陰性對照。 2)Bax干擾組的凋亡指數(shù)為19.98％，與陰性對照組相似。 結(jié)論 1、干擾Bak等凋亡分子的表達，可以抑制顆粒細胞的凋亡。 2、Bak干擾組以及BaxBak聯(lián)合干擾組抗顆粒凋亡效果顯著。 3、Bax干擾組抑制顆粒細胞凋亡的作用不明顯。 第二部分人工干預(yù)小鼠胚胎細胞凋亡 目的 通過轉(zhuǎn)染Bax-siRNA和Bak-siRNA，研究其對鼠胚凋亡的影響，尋找干預(yù)胚胎的凋亡、促進胚胎發(fā)育的新途徑。 方法 1、激光打孔轉(zhuǎn)染FAM標(biāo)記的陰性siRNA，熒光檢測轉(zhuǎn)染方法是否可行。 2、通過激光打孔分別以及同時將Bax、Bak-siRNA轉(zhuǎn)入小鼠胚胎，進行普通形態(tài)、卵裂觀察；并計算囊胚形成率。 3、通過激光打孔分別以及同時將Bax、Bak-siRNA轉(zhuǎn)染入小鼠胚胎，Hoechst33342和PI熒光染色檢測凋亡，并計數(shù)凋亡細胞。 4、免疫熒光檢測Bak、Bax的表達，并檢測其光密度與陰性對照比較。 5、分別用熒光檢測Bak及Bax干擾組中caspase-3前體的表達。 結(jié)果 1、轉(zhuǎn)染FAM標(biāo)記的陰性siRNA的胚胎有熒光，證明轉(zhuǎn)染方法有效。 2、囊胚形成率：空白對照組81.0％，陰性對照組69.5％，Bak干擾組92.5％，Bax干擾組74.0％，聯(lián)合干擾組89.5％。其中，Bak干擾組、聯(lián)合干擾組與陰性對照有顯著差異，p＜0.001；Bax干擾組與陰性對照無顯著差異，p=0.318；陰性對照與空白對照有差異，p=0.011。 3、Hoechst33342和PI染色檢測細胞凋亡：空白對照組26.0％，陰性對照組33.0％，Bak干擾組17.6％，Bax干擾組30.5％，聯(lián)合干擾組19.1％；與陰性對照組比較，Bak干擾組和聯(lián)合干擾組均有顯著差異，p＜0.001；但Bax干擾組無顯著差異，p=0.470。 4、熒光檢測Bak、Bax的表達：Bax干擾組及其陰性對照組光密度分別為25.39±4.73、52.89±3.91，前者顯著減弱p＜0.001；Bak干擾組及其陰性對照組光密度分別為：17.10±3.79、35.26±4.88，前者顯著減弱p＜0.001；聯(lián)合干擾組及其陰性對照組光密度分別為：TRITC標(biāo)記組：19.68±4.86、35.26±4.88；前者顯著減弱p＜0.001；FITC標(biāo)記組：32.78±3.73、52.89±3.91，均為前者顯著減弱p＜0.001。 5、熒光檢測caspase-3前體的表達。 Bak干擾組及其陰性對照中caspase-3光密度分別為：65.68±4.79、30.24±3.40，p＜0.001，有顯著差異；Bax干擾組及其陰性對照中caspase-3光密度分別為：31.48±2.65、30.24±3.40，p=0.318，無顯著差異。 結(jié)論 1．首次在小鼠胚胎上應(yīng)用激光打孔后轉(zhuǎn)染的實驗方法。 2．在轉(zhuǎn)染Bak／Bax-SiRNA后，Bak和Bax的表達減弱。 3．在Bak干擾和聯(lián)合干擾組中，鼠胚的凋亡細胞數(shù)明顯減少，囊胚的形成率明顯增加；而在Bax干擾組中，胚胎的凋亡細胞數(shù)、囊胚形成率與陰性對照相比無明顯改變；說明Bak干擾以及Bak-Bax聯(lián)合干擾對于抑制鼠胚的凋亡是有效的。 4．鼠胚中caspase-3前體的表達在Bak干擾組中增強；在Bax干擾組中無明顯變化。 第三部分鼠胚移植與染色體檢測 目的 1、初步研究鼠胚在進行抗凋亡處理后是否能發(fā)育至成熟個體。 2、初步觀察出生小鼠是否有生理缺陷及染色體異常。 方法 1、挑選Bak／Bax干擾組及聯(lián)合干擾組中發(fā)育較好的囊胚各10個移植入小鼠子宮；觀察出生小鼠的基本情況。 2、出生小鼠染色體的檢查。 結(jié)果 1、Bak干擾組共出生6只小鼠，Bax干擾組和聯(lián)合干擾組均出生5只小鼠，出生小鼠均無明顯畸形和行為異常。 2、出生小鼠染色體無明顯異常。 結(jié)論 1、經(jīng)Bak、Bax抗凋亡處理的鼠胚可以正常發(fā)育至成熟個體。 2、抗凋亡處理對出生小鼠無明顯影響。 3、抗凋亡處理對出生小鼠染色體無明顯影響。
[Abstract]:The aging and death of eggs and embryos is a key factor that restricts the success rate of the assisted reproductive technology (in vitro fertilization embryo transfer, IVF-ET), such as assisted reproduetive techniques (ART), and the apoptosis is the main way of egg and embryo death, and also the fertilization of egg cells. The main reasons for the stagnation of the barrier and embryo development and the failure of the implantation of the embryo can be conceived that, if the apoptosis of the eggs and embryos can be suppressed, the quality of the embryos and the success rate of assisted reproduction will be significantly increased. There are many reasons for the apoptosis, and the anti apoptotic molecules and the apoptotic molecules are very important in regulating the apoptosis of the egg cells and embryo cells. The balance between them determines the survival and death of cells. Among them, the Bcl-2 family plays an important role, Bax, Bak is a member of its subfamily, and has the role of promoting apoptosis. From a new point of view, the first proposed method of anti apoptosis artificial intervention to promote the development of embryos. We use human granulosa cells and mice. Early embryos as the research object, using gene transfection, the small molecules of apoptotic molecules such as Bax (small interfering RNA, siRNA) were transferred into RNA (small interfering RNA, siRNA) in human granulosa cells and mouse embryos, and the anti apoptosis intervention in vitro was analyzed by interfering mRNA expression of Bax and so on to enhance the content ratio of anti apoptotic molecules such as Bcl-2 and so on. The effect of measures on the development of early embryo, looking for a new way to improve the quality of egg and embryo, also lay a foundation for improving the rate of blastocyst formation in the culture of embryonic stem cells, so as to provide theoretical and experimental basis for the application of anti apoptosis intervention to the auxiliary treatment of clinical infertility.
The first part interferes with the expression of Bax-Bak gene
objective
By transfection of Bax, Bak small interfering RNA (siRNA), Bax interference, apoptosis Bak and other functions, to study its effect on the apoptosis of human granulosa cells, in order to improve the egg, to provide new way of embryo quality.
Method
1, Bax and Bak-siRNA were detected by Westernblot.
2, Bax and Bak-siRNA were transfected into human granulosa cells at the same time or at the same time. The basic morphology was observed and the apoptosis of granulosa cells was detected by flow cytometry.
3, the experiment was set up in blank control group, positive control group, negative control group, Bax interference group, Bak interference group and gax-Bak interference group.
Result
1, esternblot detection:
After transfection of Bax-siRNA and Bak-siRNA, the bands decreased, indicating that Bax and Bak contents in cells decreased.
2, basic morphological observation:
1) in the blank control group, the Bak interference group and the Bak+Bax interference group had normal morphology, mostly polygonal and fusiform, and mainly adhered to the wall.
2) the morphology of Bax interference group was basically normal, and there were a few black spots in the cytoplasm, mostly polygons and fusiform, mainly adhered to the wall.
3) in the positive control group, the cells in the negative control group became round and contracted, the cell spacing was large, and there were more black spots in the cytoplasm.
3, flow cytometry results:
1) the apoptotic index of the Bak interference group was 3.44%, and the BaxBak combined interference group had an apoptotic index of 3.97%, which was significantly lower than that of the negative control group.
2) the apoptotic index of the Bax interference group was 19.98%, which was similar to that of the negative control group.
conclusion
1, interfering with the expression of apoptotic molecules such as Bak can inhibit the apoptosis of granulosa cells.
2, Bak interference group and BaxBak combined interference group had significant effect on particle apoptosis.
3, inhibition of granulosa cell apoptosis by Bax interference group was not obvious.
The second part of artificial intervention in mouse embryonic cell apoptosis
objective
The effects of Bax-siRNA and Bak-siRNA on apoptosis of mouse embryos were studied.
Method
1, laser scanning was used to transfect FAM labeled negative siRNA, and fluorescence detection of transfection method was feasible.
2, through laser drilling, Bax and Bak-siRNA were transferred into mouse embryos at the same time, and the normal morphology and cleavage were observed, and the rate of blastocyst formation was calculated.
3, Bax and Bak-siRNA were transfected into mouse embryos by laser drilling respectively. Hoechst33342 and PI were used to detect apoptosis and apoptosis cells were counted.
4, the expression of Bak and Bax was detected by immunofluorescence and the optical density was compared with that of negative control.
5, the expression of Caspase-3 precursor in Bak and Bax interference groups was detected by fluorescence.
Result
1, transfected FAM labeled negative siRNA embryos showed fluorescence, indicating that the transfection method was effective.
2, the rate of blastocyst formation: blank control group 81%, negative control group 69.5%, Bak interference group 92.5%, Bax interference group 74%, combined interference group 89.5%., Bak interference group, combined interference group and negative control has significant difference, P < 0.001; Bax interference group and negative control no significant difference, p=0.318; negative control and blank control is different, p= 0.011.
3, Hoechst33342 and PI staining detected cell apoptosis: blank control group 26%, negative control group 33%, Bak interference group 17.6%, Bax interference group 30.5%, combined interference group 19.1%, compared with negative control group, Bak interference group and combined interference group were significantly different, P < 0.001; Bax interference group had no significant difference, p=0.470.
4, the expression of fluorescence detection Bak, Bax: the light density of Bax interference group and negative control group was 25.39 + 4.73,52.89 + 3.91 respectively, the former significantly weakened P < 0.001; the light density of Bak interference group and negative control group was 17.10 + 3.79,35.26 + 4.88, the former significantly weakened P < 0.001; the light density of the combined interference group and the negative control group was respectively. : TRITC tag group: 19.68 + 4.86,35.26 + 4.88; the former decreased P < 0.001; FITC tag group: 32.78 + 3.73,52.89 + 3.91, the former was significantly reduced P < 0.001.
5, the expression of Caspase-3 precursor was detected by fluorescence.
The Bak interference group and the negative control in the caspase-3 optical density was 65.68 + 4.79,30.24 + 3.40, P < 0.001, there are significant differences; the Bax interference group and the negative control in the caspase-3 optical density was 31.48 + 2.65,30.24 + 3.40, p=0.318, no significant difference.
conclusion
1. it is the first time to apply laser drilling to transfect mouse embryos.
2. after transfection of Bak / Bax-SiRNA, the expression of Bak and Bax decreased.
3. in Bak interference and combined interference group, the number of apoptotic cells in mouse embryos decreased significantly, and the rate of blastocyst formation was obviously increased. In the Bax interference group, the number of apoptotic cells, the rate of blastocyst formation and the negative ratio were not significantly changed, indicating that Bak interference and Bak-Bax interference were effective in inhibiting the apoptosis of rat embryos.
4. the expression of Caspase-3 precursor in mouse embryos increased in the Bak interference group, but there was no significant change in the Bax interference group.
The third part of mouse embryo transfer and chromosome detection
objective
1, we can preliminarily study whether mouse embryos can develop to mature individuals after anti apoptotic treatment.
2, we initially observed whether the birth mice had physiological defects and chromosomal abnormalities.
Method
1, in the Bak / Bax interference group and the combined interference group, 10 blastocysts with better blastocyst were transplanted into the mouse uterus, and the basic conditions of the mice were observed.
2, the examination of the chromosomes of the born mice.
Result
1, 6 mice were born in the Bak interference group, 5 mice were born in the Bax interference group and the combined interference group.
2, there were no obvious abnormalities in the chromosomes of the mice born.
conclusion
1, the anti apoptotic mouse embryos developed by Bak and Bax can normally develop to mature individuals.
2, the anti apoptosis treatment had no obvious effect on the birth mice.
3, the anti apoptotic treatment had no obvious effect on the chromosomes of the born mice.
【學(xué)位授予單位】：南方醫(yī)科大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2007
【分類號】：R321-33

【相似文獻】

相關(guān)期刊論文 前10條

1 丁曉潔;顧曉靜;杜奉榮;;高壓氧對腦缺血再灌注后神經(jīng)細胞凋亡的影響[J];黑龍江醫(yī)藥;2011年04期

2 舒琦瑾;李萍;王彬彬;;南方紅豆杉水提物誘導(dǎo)人肺癌A549細胞凋亡及其分子機制的實驗研究[J];中國中西醫(yī)結(jié)合雜志;2011年09期

3 練海東;任兵;高曉唯;郭繼華;解玉軍;張改麗;趙旭東;劉瑩;;米諾環(huán)素對糖尿病大鼠視網(wǎng)膜神經(jīng)細胞凋亡的影響[J];現(xiàn)代生物醫(yī)學(xué)進展;2011年13期

4 張武;朱建華;;雷公藤甲素誘導(dǎo)大鼠腎上腺皮質(zhì)細胞凋亡研究[J];遼寧中醫(yī)藥大學(xué)學(xué)報;2011年07期

5 郭建紅;楊麗紅;;脂多糖對非酒精性脂肪性肝炎大鼠肝細胞凋亡的影響[J];山西醫(yī)科大學(xué)學(xué)報;2011年07期

6 徐瑾;于蓮珍;唐玉林;王海洋;吳雨潔;楊樹平;;2-DG對體外培養(yǎng)人食管癌細胞周期及凋亡的影響[J];南京醫(yī)科大學(xué)學(xué)報(自然科學(xué)版);2011年08期

7 韓純杰;王凱;秦秀龍;馬慧勇;曹江龍;;軟骨終板細胞凋亡與頸椎間盤退變關(guān)系的研究[J];長治醫(yī)學(xué)院學(xué)報;2011年04期

8 李威;季小彬;叢晶;吳效科;;甘草次酸、水飛薊賓對體外培養(yǎng)的胰島素抵抗豬卵巢顆粒細胞的影響[J];科技導(dǎo)報;2011年19期

9 李淑芬;孫國瑛;周勇;周慧芳;段佳熙;管茶香;;TREM-2對小鼠肺成纖維細胞凋亡的影響[J];國際病理科學(xué)與臨床雜志;2011年04期

10 劉占國;張婕;何懿;常平;顧冬生;羅宇維;孫爾維;;凋亡和壞死細胞輸注對膿毒癥小鼠存活率的影響[J];南方醫(yī)科大學(xué)學(xué)報;2011年06期

相關(guān)會議論文 前10條

1 潘伯臣;葉瑩心;何麗霞;趙冬妮;楊大磊;王秀霞;張淑蘭;;人黃素化顆粒細胞中HB-EGF及其受體的表達[A];第八次全國婦產(chǎn)科學(xué)學(xué)術(shù)會議論文匯編[C];2004年

2 盧翠玲;劉以訓(xùn);;Inhibin-α可能通過調(diào)節(jié)FSHR的表達,從而調(diào)節(jié)FSH的作用[A];第十屆全國生殖生物學(xué)學(xué)術(shù)研討會論文摘要集[C];2005年

3 李蕾;李尚為;靳松;秦朗;黃仲英;馬黔紅;李培旭;;應(yīng)用顆粒細胞部分剝除法提高常規(guī)體外受精-胚胎移植(IVF-ET)胚胎質(zhì)量和妊娠率的實驗研究[A];第二屆全國不育癥研討會論文匯編[C];2007年

4 韓春錫;廖建湘;韓春錫;河西奈保子;小林未明;鳥光慶一;文善姬;;移植的齒狀回顆粒細胞在體外培養(yǎng)的大鼠海馬組織切片上移行特征[A];中華醫(yī)學(xué)會第十四次全國兒科學(xué)術(shù)會議論文匯編[C];2006年

5 章曉梅;鄧蓮;李春華;李永剛;馬艷萍;高夢瑩;馮懷瑛;;妊娠相關(guān)血漿蛋白-A與卵泡刺激素在卵泡發(fā)育中的關(guān)系[A];澳門、香港、內(nèi)地生殖健康研討會論文集[C];2004年

6 吳敏秋;王子軾;武彩紅;張斌;;顆粒細胞的去除方法對豬成熟卵母細胞冷凍效果的影響[A];中國畜牧獸醫(yī)學(xué)會小動物醫(yī)學(xué)分會第四次學(xué)術(shù)研討會、中國畜牧獸醫(yī)學(xué)會獸醫(yī)外科學(xué)分會第十六次學(xué)術(shù)研討會論文集（1）[C];2009年

7 薛曉鷗;楊毅;艾浩;李健;牛建昭;王繼峰;;順鉑對正常大鼠卵巢顆粒細胞的毒性和金雀黃素的保護作用[A];第八屆全國中西醫(yī)結(jié)合實驗醫(yī)學(xué)研討會論文匯編[C];2006年

8 許峰;朱遂強;康慧聰;;鋰-匹魯卡品致癇促進大鼠齒狀回顆粒細胞神經(jīng)生發(fā)[A];第九次全國神經(jīng)病學(xué)學(xué)術(shù)大會論文匯編[C];2006年

9 王春生;李晶;張滕子;寧方勇;樸善花;安鐵洙;;擬蜘蛛絲蛋白基因在小鼠顆粒細胞中的整合及其鑒定[A];中國畜牧獸醫(yī)學(xué)會動物解剖學(xué)及組織胚胎學(xué)分會第十六次學(xué)術(shù)研討會論文集[C];2010年

10 易康樂;陳華海;李純錦;孫艷玲;陳露;石德順;周虛;;BDNF和NGF對牛顆粒細胞體外生長的影響[A];中國畜牧獸醫(yī)學(xué)會動物繁殖學(xué)分會第十五屆學(xué)術(shù)研討會論文集（下冊）[C];2010年

相關(guān)重要報紙文章 前10條

1 陸文;凋亡細胞 被擠出上皮組織[N];醫(yī)藥經(jīng)濟報;2002年

2 張荔子;終端分化細胞克隆小鼠成功[N];健康報;2006年

3 洪敏;細胞凋亡研究引人關(guān)注[N];中國醫(yī)藥報;2008年

4 常麗君;基因在腦記憶區(qū)發(fā)育中扮關(guān)鍵角色[N];科技日報;2010年

5 宋立新;生育中有余與不足的相互補償[N];大眾科技報;2001年

6 北京協(xié)和醫(yī)院 主管檢驗技師 張時民;白細胞是如何分類的[N];家庭醫(yī)生報;2005年

7 吳一福;廣東惠州學(xué)院實驗表明:黃芪注射液可改善腹透療效[N];中國醫(yī)藥報;2005年

8 白毅;TRPC通道參與保護小腦神經(jīng)元[N];中國醫(yī)藥報;2007年

9 張時民;專家教您學(xué)看化驗單[N];農(nóng)村醫(yī)藥報（漢）;2008年

10 ;臺灣用自體細胞粒腺體置換技術(shù)治療不孕癥[N];中國高新技術(shù)產(chǎn)業(yè)導(dǎo)報;2002年

相關(guān)博士學(xué)位論文 前10條

1 齊軍元;骨髓增生異常綜合征細胞凋亡的研究[D];中國協(xié)和醫(yī)科大學(xué);1999年

2 安立峰;特異性的抑制AQP1對喉癌細胞的生長抑制作用[D];吉林大學(xué);2007年

3 孫巍;蒺藜皂苷對心肌缺血的保護作用及其分子機制研究[D];吉林大學(xué);2007年

4 龍新兵;平衡針療法對顱腦損傷急性期影響的研究[D];廣州中醫(yī)藥大學(xué);2007年

5 白宇;白藜蘆醇對人膀胱癌T24細胞的抑制作用及其機制研究[D];浙江大學(xué);2008年

6 陳琰;外源性PUMA表達增加HPV陽性宮頸癌放療敏感性的體外研究[D];中國協(xié)和醫(yī)科大學(xué);2008年

7 李紅;人工抗凋亡促進胚胎發(fā)育的研究[D];南方醫(yī)科大學(xué);2007年

8 慈光新;抗氧化性生物活性物質(zhì)對雞等級前卵泡細胞發(fā)育的影響及其機理的研究[D];浙江大學(xué);2009年

9 馮雪瑩;小鼠巨噬細胞吞噬凋亡細胞的炎癥調(diào)節(jié)及性別差異[D];北京協(xié)和醫(yī)學(xué)院;2011年

10 孔令紅;人自體顆粒細胞線粒體移植改善卵子質(zhì)量和胚胎發(fā)育的研究[D];第一軍醫(yī)大學(xué);2004年

相關(guān)碩士學(xué)位論文 前10條

1 霍道坦;胎豬卵巢發(fā)育早期細胞凋亡的研究[D];安徽農(nóng)業(yè)大學(xué);2008年

2 劉海洋;內(nèi)質(zhì)網(wǎng)應(yīng)激參與視網(wǎng)膜脫離后細胞凋亡的研究[D];上海交通大學(xué);2007年

3 張仁民;納秒級高壓陡脈沖裝置及其誘導(dǎo)腫瘤細胞凋亡效應(yīng)的研究[D];重慶大學(xué);2007年

4 孫臻峰;雷諾考特致鼻息肉成纖維細胞凋亡的實驗研究[D];第二軍醫(yī)大學(xué);2007年

5 王鵬;克羅卡林對大鼠腦缺血再灌注損傷的保護作用及其機制研究[D];青島大學(xué);2009年

6 麻小浩;ADFMChR對人肺癌A549細胞生長和凋亡的影響[D];湖南師范大學(xué);2009年

7 兌宏志;鹽酸戊乙奎醚對大鼠心肌微血管內(nèi)皮細胞缺氧/復(fù)氧后凋亡的影響[D];第四軍醫(yī)大學(xué);2009年

8 劉勝勇;9-順式維甲酸和維生素D3對神經(jīng)母細胞瘤細胞系體外生長的協(xié)同抑制作用[D];安徽醫(yī)科大學(xué);2009年

9 韓慧敏;腫瘤壞死因子（TNF-α）對耐藥腫瘤細胞凋亡誘導(dǎo)作用的研究[D];大連醫(yī)科大學(xué);2007年

10 張帆;熊果酸誘導(dǎo)人胃癌BGC-803細胞凋亡及機制研究[D];內(nèi)蒙古醫(yī)學(xué)院;2007年

本文編號：2045373