大鼠miR-185-3p調(diào)控的TrkB.FL信號通路抑制神經(jīng)元癇樣放電的研究
發(fā)布時間：2018-08-11 09:21
【摘要】：研究目的： 癲癇(Epilepsy)是一種常見的神經(jīng)系統(tǒng)疾病,在研究癲癇發(fā)病機制的基礎(chǔ)上,探索抑制癲癇發(fā)作的有效途徑,具有重要的科學意義和臨床應用價值。本論文在癲癇發(fā)生的TrkB (tropomyosin-related kinase B)受體和TrkB信號通路角度,以大鼠海馬神經(jīng)元癇樣放電模型(spontaneous recurrent epileptiform discharges, SREDs)為研究對象,通過大鼠miR-185-3p(miR-185*)激活全長型TrkB(TrkB.FL)信號通路,研究神經(jīng)元電壓門控性Ca2+通道(Voltage-gated calcium channels, VGCCs)特性和癇樣放電的抑制情況。探討TrkB.FL信號通路激活后抑制癲癇發(fā)生的機制,為臨床治療癲癇提供創(chuàng)新的調(diào)控思路。 研究方法： 1.通過無鎂液處理原代培養(yǎng)的大鼠海馬神經(jīng)元3h,構(gòu)建神經(jīng)元癇樣放電模型。 2.研究TrkB受體和TrkB信號通路在癇樣放電模型中的變化機制。 (1)通過實時熒光定量PCR和western blotting檢測全長型TrkB(TrkB.FL)和截短型TrkB(TrkB.T)受體在模型中的表達水平,并應用鈣蛋白酶抑制劑和轉(zhuǎn)錄翻譯抑制劑研究調(diào)控TrkB受體表達變化的機制。 (2)使用BDNF處理模型,應用western blotting檢測磷酸化TrkB.FL受體蛋白的表達水平,研究模型中TrkB受體表達變化調(diào)控TrkB.FL信號通路活性的相關(guān)機制。 3.研究miR-185*調(diào)控TrkB.FL信號通路活性后對癇樣放電的影響。 (1)利用包含miR-185*-pGLVHl/GFP表達載體的慢病毒轉(zhuǎn)染模型,實時熒光定量PCR和western blotting檢測TrkB.T受體表達和TrkB.FL信號通路活性的改變。 (2)全細胞膜片鉗檢測miR-185*轉(zhuǎn)染模型中神經(jīng)元VGCC電流和穩(wěn)態(tài)激活與失活特性的變化。 (3)全細胞膜片鉗檢測miR-185*轉(zhuǎn)染模型中神經(jīng)元放電的頻率變化情況。 4.應用翻譯抑制劑孵育癇樣放電模型,通過全細胞膜片鉗檢測神經(jīng)元放電頻率的變化,研究TrkB.FL信號通路活性改變后對癇樣放電的影響。 研究結(jié)果： 1.大鼠海馬神經(jīng)元癇樣放電模型的鑒定結(jié)果： 與正常對照組神經(jīng)元相比,模型組中神經(jīng)元放電頻率顯著上升(P0.001, n=9), inter-event interval累計分布曲線明顯左移(P0.001,n=9)。 2.TrkB受體和TrkB信號通路在癇樣放電模型中的變化結(jié)果： (1)在癇樣放電模型中,TrkB.T受體較正常對照組表達增加(P0.001,n=6),TrkB.FL受體表達降低(P0.001,n=6)。與模型組相比,鈣蛋白酶抑制劑孵育模型后,TrkB.FL受體表達上升(P0.001,n=6)；轉(zhuǎn)錄或翻譯抑制劑孵育模型后,TrkB.T受體表達均下降(P0.001,n=6)。 (2)與正常對照孵育BDNF組相比,BDNF處理癇樣放電模型,或者BDNF處理模型再孵育鈣蛋白酶抑制劑,以上兩組磷酸化的TrkB.FL受體蛋白與總TrkB.FL受體蛋白的比值(pTrkB.FL/total TrkB.FL)均降低(P0.01,n=6),證明TrkB.FL信號通路活性被抑制。而BDNF處理癇樣放電模型再孵育翻譯抑制劑后,與BDNF處理模型組相比,pTrkB.FL/total TrkB.FL比值升高(P0.001, n=6), TrkB.FL信號通路被激活。 3.利用miR-185*調(diào)控TrkB.FL信號通路活性后影響癇樣放電的研究結(jié)果： (1)利用miR-185*轉(zhuǎn)染癇樣放電模型72h后,miR-185*在模型中持續(xù)大量的表達,并調(diào)控模型中TrkB.T受體表達減少(P0.001, n=6)。miR-185*轉(zhuǎn)染癇樣放電模型后再經(jīng)BDNF處理,與BDNF處理模型組相比,pTrkB.FL/total TrkB.FL比值上升(P0.001,n=4),TrkB.FL信號通路同樣被激活。 (2)癇樣放電模型組中神經(jīng)元VGCC電流和穩(wěn)態(tài)激活與失活特性的相關(guān)參數(shù)與正常對照組比較后發(fā)現(xiàn),VGCC最大電流密度升高(P0.001,n=10-15)；激活曲線的V1/2和斜率因子k顯著降低(P0.001,n=7-10)。表示VGCC激活的閾電位減小,激活速度加快,通道相對容易被激活。模型組VGCC失活曲線的V1/2顯著增加(P0.001,n=7-9),而斜率因子k卻顯著降低(P0.001,n=7-9)。表示VGCC失活的閾電位增加,失活速度變慢,通道相對更難失活。 而miR-185*轉(zhuǎn)染癇樣放電模型后,VGCC特性的相關(guān)參數(shù)與未經(jīng)轉(zhuǎn)染的模型組相比,VGCC最大電流密度降低(P0.001,n=10.15)；激活曲線的V1/2顯著增加(P0.01,n=7-10),斜率因子k也顯著升高(P0.001,n=7-10)。表示VGCC激活的閾電位升高,激活速度降低,通道相對難以激活。而VGCC失活曲線的V1/2變化雖然降低,但不顯著(P0.05,n=7-9),反而斜率因子k顯著升高(P0.05,n=7-9),表明VGCC失活速度加快,通道相對更容易失活。 (3)miR-185*轉(zhuǎn)染癇樣放電模型后,與未經(jīng)處理的模型相比,神經(jīng)元放電頻率顯著降低(P0.001,n=9),其inter-event interval累計分布曲線右移(P0.001,n=9),結(jié)果顯示轉(zhuǎn)染模型神經(jīng)元的癇樣放電減弱。 4.應用翻譯抑制劑孵育癇樣放電模型,TrkB.FL信號通路變化后對癇樣放電的調(diào)節(jié)結(jié)果： 與未經(jīng)處理的模型相比,翻譯抑制劑孵育模型后的神經(jīng)元放電頻率顯著降低(P0.001,n=9), inter-event interval累計分布曲線右移(P0.001,n=9),神經(jīng)元的癇樣放電同樣減弱。 結(jié)論： 1.大鼠海馬神經(jīng)元經(jīng)無鎂液處理3h后,成功構(gòu)建癇樣放電模型。 2.癇樣放電模型中,鈣蛋白酶調(diào)控TrkB.FL受體表達減少,轉(zhuǎn)錄翻譯過程參與 TrkB.T受體表達的增加。TrkB.T受體的高表達抑制模型中TrkB.FL信號通路的激活。 3.miR-185*激活TrkB.FL信號通路后,抑制癇樣放電的產(chǎn)生。 (1)miR-185*轉(zhuǎn)染癇樣放電模型,通過下調(diào)TrkB.T受體的表達,可以激活TrkB.FL信號通路。 (2)激活的TrkB.FL信號通路抑制miR-185*轉(zhuǎn)染模型神經(jīng)元的VGCC電流和通道活性。 (3)激活的TrkB.FL信號通路降低miR-185*轉(zhuǎn)染模型神經(jīng)元的放電頻率。 4.翻譯抑制劑孵育癇樣放電模型,激活的TrkB.FL信號通路同樣降低了神經(jīng)元的放電頻率,最終抑制癇樣放電。
[Abstract]:Research purposes:
Epilepsy is a common nervous system disease. Based on the study of the pathogenesis of epilepsy, it is of great scientific significance and clinical value to explore effective ways to inhibit epileptic seizures. The spontaneous recurrent epileptiform discharges (SREDs) were used to study the characteristics of voltage-gated Ca2+ channels (VGCCs) and the inhibition of epileptiform discharges in neurons by activating the full-length TrkB (TrkB.FL) signaling pathway with rat microRNA185-3p (microRNA185*). The mechanism of inhibiting epilepsy after pathway activation provides innovative regulatory ideas for clinical treatment of epilepsy.
Research methods:
1. The epileptiform discharge model of primary cultured rat hippocampal neurons was established by treating them with magnesium-free solution for 3 hours.
2. to study the mechanism of TrkB receptor and TrkB signaling pathway in epileptiform discharges.
(1) The expression levels of full-length TrkB (TrkB.FL) and truncated TrkB (TrkB.T) receptors were detected by real-time fluorescence quantitative PCR and Western blotting. Calpain inhibitors and transcriptional translation inhibitors were used to study the mechanism of regulating the expression of TrkB receptors.
(2) Western blotting was used to detect the expression of phosphorylated TrkB.FL receptor protein in BDNF treatment model, and the mechanism of TrkB.FL signaling pathway activity was studied.
3. to study the effect of miR-185* on the epileptiform discharges after regulating the activity of TrkB.FL signaling pathway.
(1) The expression of TrkB.T receptor and the activity of TrkB.FL signaling pathway were detected by real-time fluorescence quantitative PCR and Western blotting using a lentiviral transfection model containing the expression vector of Mi-185*-pGLVHl/GFP.
(2) Whole-cell patch clamp technique was used to detect the changes of VGCC current and steady-state activation and inactivation of neurons in the model of microarray-185 * transfection.
(3) whole cell patch clamp test was used to detect the frequency of neuronal firing in miR-185* transfection model.
4. Using the model of epileptiform discharges incubated by translation inhibitors, the changes of neuronal discharge frequencies were detected by whole-cell patch clamp to study the effects of changes in TrkB.FL signaling pathway activity on epileptiform discharges.
Research findings:
1. the epileptic discharge model of rat hippocampal neurons was identified.
Compared with the normal control group, the discharge frequency of neurons in the model group increased significantly (P 0.001, n = 9), and the cumulative distribution curve of inter-event interval shifted significantly to the left (P 0.001, n = 9).
The changes of 2.TrkB receptor and TrkB signaling pathway in epileptiform discharges model:
(1) In the epileptiform discharge model, the expression of TrkB.T receptor increased (P 0.001, n = 6) and the expression of TrkB.FL receptor decreased (P 0.001, n = 6) compared with the normal control group.
(2) The ratio of phosphorylated TrkB.FL receptor protein to total TrkB.FL receptor protein (pTrkB.FL/total TrkB.FL) in BDNF-treated epileptiform discharges model or BDNF-treated model was lower than that in BDNF-treated group (P 0.01, n=6), suggesting that the activity of TrkB.FL signaling pathway was inhibited. The ratio of pTrkB.FL/total TrkB.FL increased (P 0.001, n=6) and the TrkB.FL signaling pathway was activated in the BDNF treated group after incubation of the TrkB.FL inhibitor.
3. using miR-185* to regulate the activity of TrkB.FL signaling pathway, the results of epileptiform discharges were studied.
(1) After 72 hours of transfection of epileptiform discharge model with microRNAs-185 * the expression of microRNAs-185 * in the model continued to increase, and the expression of TrkB.T receptor decreased (P 0.001, n = 6). After transfection of epileptiform discharge model with microRNAs-185 * and BDNF treatment, the ratio of pTrkB.FL/total TrkB.FL increased (P 0.001, n = 4), and the TrkB.FL signaling pathway was the same as that of BDNF treatment group. Activated.
(2) Compared with the normal control group, the parameters related to VGCC current and steady-state activation and inactivation of neurons in the epileptiform discharge model group showed that the maximum current density of VGCC increased (P 0.001, n = 10-15), and the V1/2 and slope factor K of activation curve decreased significantly (P 0.001, n = 7-10). V1/2 of the VGCC inactivation curve increased significantly (P 0.001, n=7-9) while the slope factor K decreased significantly (P 0.001, n=7-9). This indicated that the threshold potential of VGCC inactivation increased, the inactivation rate slowed down, and the channel was relatively more difficult to inactivate.
Compared with the untransfected group, the maximum current density of VGCC decreased (P 0.001, n = 10.15), the V1/2 of the activation curve increased significantly (P 0.01, n = 7-10), and the slope factor K increased significantly (P 0.001, n = 7-10). V1/2 of VGCC inactivation curve decreased, but not significantly (P 0.05, n = 7-9), but the slope factor K increased significantly (P 0.05, n = 7-9), indicating that VGCC inactivation speed increased, and the channel was relatively easier to inactivate.
(3) Compared with untreated model, the discharge frequency of neurons was significantly decreased (P 0.001, n = 9) and the cumulative distribution curve of inter-event interval shifted to the right (P 0.001, n = 9) after transfection of microRNA185* into the epileptiform discharge model. The results showed that the epileptiform discharge of neurons in the transfected model was decreased.
4. Using the model of epileptiform discharges incubated by translation inhibitors, the regulation of TrkB.FL signaling pathway on epileptiform discharges was studied.
Compared with the untreated model, the firing frequency of the neurons incubated with the translation inhibitor decreased significantly (P 0.001, n=9), the cumulative distribution curve of inter-event interval shifted to the right (P 0.001, n=9), and the epileptiform discharge of the neurons also decreased.
Conclusion:
1. rat hippocampal neurons were treated with magnesium free solution for 3h, and epileptiform discharges were successfully constructed.
2. In the epileptiform discharge model, the expression of TrkB.FL receptor is decreased and transcriptional translation is involved.
Increased expression of TrkB.T receptor. Activation of TrkB.FL signaling pathway in the TrkB.T receptor overexpression inhibition model.
3.miR-185* activates the TrkB.FL signaling pathway and suppresses epileptiform discharges.
(1) Mi-185* transfected epileptiform discharge model can activate TrkB.FL signaling pathway by down-regulating the expression of TrkB.T receptor.
(2) Activated TrkB.FL signaling pathway inhibits the VGCC current and channel activity in the model neurons transfected with miR-185*
(3) activation of TrkB.FL signaling pathway reduces the firing frequency of neurons in miR-185* transfection model.
4. Translator inhibitors incubate epileptiform discharges. Activated TrkB.FL signaling pathway also reduces the frequency of neuronal discharges and ultimately inhibits epileptiform discharges.
【學位授予單位】：天津醫(yī)科大學
【學位級別】：博士
【學位授予年份】：2014
【分類號】：R742.1
本文編號：2176573
[Abstract]:Research purposes:
Epilepsy is a common nervous system disease. Based on the study of the pathogenesis of epilepsy, it is of great scientific significance and clinical value to explore effective ways to inhibit epileptic seizures. The spontaneous recurrent epileptiform discharges (SREDs) were used to study the characteristics of voltage-gated Ca2+ channels (VGCCs) and the inhibition of epileptiform discharges in neurons by activating the full-length TrkB (TrkB.FL) signaling pathway with rat microRNA185-3p (microRNA185*). The mechanism of inhibiting epilepsy after pathway activation provides innovative regulatory ideas for clinical treatment of epilepsy.
Research methods:
1. The epileptiform discharge model of primary cultured rat hippocampal neurons was established by treating them with magnesium-free solution for 3 hours.
2. to study the mechanism of TrkB receptor and TrkB signaling pathway in epileptiform discharges.
(1) The expression levels of full-length TrkB (TrkB.FL) and truncated TrkB (TrkB.T) receptors were detected by real-time fluorescence quantitative PCR and Western blotting. Calpain inhibitors and transcriptional translation inhibitors were used to study the mechanism of regulating the expression of TrkB receptors.
(2) Western blotting was used to detect the expression of phosphorylated TrkB.FL receptor protein in BDNF treatment model, and the mechanism of TrkB.FL signaling pathway activity was studied.
3. to study the effect of miR-185* on the epileptiform discharges after regulating the activity of TrkB.FL signaling pathway.
(1) The expression of TrkB.T receptor and the activity of TrkB.FL signaling pathway were detected by real-time fluorescence quantitative PCR and Western blotting using a lentiviral transfection model containing the expression vector of Mi-185*-pGLVHl/GFP.
(2) Whole-cell patch clamp technique was used to detect the changes of VGCC current and steady-state activation and inactivation of neurons in the model of microarray-185 * transfection.
(3) whole cell patch clamp test was used to detect the frequency of neuronal firing in miR-185* transfection model.
4. Using the model of epileptiform discharges incubated by translation inhibitors, the changes of neuronal discharge frequencies were detected by whole-cell patch clamp to study the effects of changes in TrkB.FL signaling pathway activity on epileptiform discharges.
Research findings:
1. the epileptic discharge model of rat hippocampal neurons was identified.
Compared with the normal control group, the discharge frequency of neurons in the model group increased significantly (P 0.001, n = 9), and the cumulative distribution curve of inter-event interval shifted significantly to the left (P 0.001, n = 9).
The changes of 2.TrkB receptor and TrkB signaling pathway in epileptiform discharges model:
(1) In the epileptiform discharge model, the expression of TrkB.T receptor increased (P 0.001, n = 6) and the expression of TrkB.FL receptor decreased (P 0.001, n = 6) compared with the normal control group.
(2) The ratio of phosphorylated TrkB.FL receptor protein to total TrkB.FL receptor protein (pTrkB.FL/total TrkB.FL) in BDNF-treated epileptiform discharges model or BDNF-treated model was lower than that in BDNF-treated group (P 0.01, n=6), suggesting that the activity of TrkB.FL signaling pathway was inhibited. The ratio of pTrkB.FL/total TrkB.FL increased (P 0.001, n=6) and the TrkB.FL signaling pathway was activated in the BDNF treated group after incubation of the TrkB.FL inhibitor.
3. using miR-185* to regulate the activity of TrkB.FL signaling pathway, the results of epileptiform discharges were studied.
(1) After 72 hours of transfection of epileptiform discharge model with microRNAs-185 * the expression of microRNAs-185 * in the model continued to increase, and the expression of TrkB.T receptor decreased (P 0.001, n = 6). After transfection of epileptiform discharge model with microRNAs-185 * and BDNF treatment, the ratio of pTrkB.FL/total TrkB.FL increased (P 0.001, n = 4), and the TrkB.FL signaling pathway was the same as that of BDNF treatment group. Activated.
(2) Compared with the normal control group, the parameters related to VGCC current and steady-state activation and inactivation of neurons in the epileptiform discharge model group showed that the maximum current density of VGCC increased (P 0.001, n = 10-15), and the V1/2 and slope factor K of activation curve decreased significantly (P 0.001, n = 7-10). V1/2 of the VGCC inactivation curve increased significantly (P 0.001, n=7-9) while the slope factor K decreased significantly (P 0.001, n=7-9). This indicated that the threshold potential of VGCC inactivation increased, the inactivation rate slowed down, and the channel was relatively more difficult to inactivate.
Compared with the untransfected group, the maximum current density of VGCC decreased (P 0.001, n = 10.15), the V1/2 of the activation curve increased significantly (P 0.01, n = 7-10), and the slope factor K increased significantly (P 0.001, n = 7-10). V1/2 of VGCC inactivation curve decreased, but not significantly (P 0.05, n = 7-9), but the slope factor K increased significantly (P 0.05, n = 7-9), indicating that VGCC inactivation speed increased, and the channel was relatively easier to inactivate.
(3) Compared with untreated model, the discharge frequency of neurons was significantly decreased (P 0.001, n = 9) and the cumulative distribution curve of inter-event interval shifted to the right (P 0.001, n = 9) after transfection of microRNA185* into the epileptiform discharge model. The results showed that the epileptiform discharge of neurons in the transfected model was decreased.
4. Using the model of epileptiform discharges incubated by translation inhibitors, the regulation of TrkB.FL signaling pathway on epileptiform discharges was studied.
Compared with the untreated model, the firing frequency of the neurons incubated with the translation inhibitor decreased significantly (P 0.001, n=9), the cumulative distribution curve of inter-event interval shifted to the right (P 0.001, n=9), and the epileptiform discharge of the neurons also decreased.
Conclusion:
1. rat hippocampal neurons were treated with magnesium free solution for 3h, and epileptiform discharges were successfully constructed.
2. In the epileptiform discharge model, the expression of TrkB.FL receptor is decreased and transcriptional translation is involved.
Increased expression of TrkB.T receptor. Activation of TrkB.FL signaling pathway in the TrkB.T receptor overexpression inhibition model.
3.miR-185* activates the TrkB.FL signaling pathway and suppresses epileptiform discharges.
(1) Mi-185* transfected epileptiform discharge model can activate TrkB.FL signaling pathway by down-regulating the expression of TrkB.T receptor.
(2) Activated TrkB.FL signaling pathway inhibits the VGCC current and channel activity in the model neurons transfected with miR-185*
(3) activation of TrkB.FL signaling pathway reduces the firing frequency of neurons in miR-185* transfection model.
4. Translator inhibitors incubate epileptiform discharges. Activated TrkB.FL signaling pathway also reduces the frequency of neuronal discharges and ultimately inhibits epileptiform discharges.
【學位授予單位】：天津醫(yī)科大學
【學位級別】：博士
【學位授予年份】：2014
【分類號】：R742.1
【共引文獻】
相關(guān)期刊論文 前10條
1 吳春蓉;羅治彬;;腫瘤相關(guān)性microRNA在胃癌研究中的新進展[J];國際消化病雜志;2010年01期
2 彭雅亞;;AKT-1在乳腺良惡性病變中的表達及其臨床意義[J];標記免疫分析與臨床;2013年04期
3 隗黎麗;吳華東;熊六鳳;;柱狀黃桿菌對草魚TLRs基因表達水平的影響[J];大連海洋大學學報;2013年04期
4 謝婧雯;劉曉燕;;Akt信號轉(zhuǎn)導通路在心血管系統(tǒng)中作用的研究進展[J];重慶醫(yī)學;2013年30期
5 廖萌;嚴孫杰;;成骨細胞Toll樣受體4信號通路研究進展[J];中華骨質(zhì)疏松和骨礦鹽疾病雜志;2013年03期
6 李致宏;馬振剛;李晚軍;劉軍;韓冰;李田;潘國慶;李春峰;周澤揚;;感染家蠶微孢子蟲的蠶體血淋巴蛋白質(zhì)差異表達分析及質(zhì)譜鑒定[J];蠶業(yè)科學;2013年05期
7 余夢辰;李斌;周紅;;內(nèi)毒素識別、內(nèi)化及清除相關(guān)受體的研究進展[J];重慶醫(yī)學;2013年29期
8 肖玲;舒暢;唐記華;王曉萍;王高華;;不同時程的慢性不可預計溫和應激對大鼠海馬神經(jīng)可塑性相關(guān)蛋白水平的影響[J];神經(jīng)損傷與功能重建;2013年06期
9 馮婭妮;孫艷紅;馬虹;;丙泊酚預處理對SK-N-SH神經(jīng)母細胞缺氧/復氧損傷的保護作用[J];廣東醫(yī)學;2013年22期
10 王德勇;徐慧高;;Akt/mTOR信號通路與口腔鱗狀細胞癌的研究進展[J];蚌埠醫(yī)學院學報;2013年11期
相關(guān)會議論文 前1條
1 Wei Long;Jinhang Zan;Zewei Zhou;Xin He;Jin Jin;Saijun Fan;Peixun Liu;;Computational Simulation for Binding Interaction of TLR5 with Flagellin[A];第二屆國際計算科學與工程國際學術(shù)研討會論文集[C];2013年
相關(guān)博士學位論文 前10條
1 周嘉梁;MicroRNA-142-3p對結(jié)直腸癌生物學行為的影響及作用機制的初步研究[D];蘇州大學;2013年
2 李蓮蓮;感覺神經(jīng)節(jié)對腦運動神經(jīng)元軸突生長的影響及其分子機制[D];蘭州大學;2013年
3 宗燦華;奶牛乳腺主要乳成分合成代謝的轉(zhuǎn)錄組學研究[D];東北農(nóng)業(yè)大學;2013年
4 趙一萍;蒙古馬免疫相關(guān)基因表達研究及脾臟表達譜分析[D];內(nèi)蒙古農(nóng)業(yè)大學;2013年
5 薛雪;AQP4基因缺失對中腦TGF-β產(chǎn)生的影響及其與帕金森疾病的相關(guān)研究[D];南京醫(yī)科大學;2013年
6 王晶晶;中華絨螯蟹免疫致敏現(xiàn)象及相關(guān)分子機制的初步研究[D];中國科學院研究生院（海洋研究所）;2013年
7 王雷雷;扇貝補體相關(guān)分子的結(jié)構(gòu)及功能研究[D];中國科學院研究生院（海洋研究所）;2013年
8 袁世英;AMPK信號通路在大鼠慢性糖皮質(zhì)激素應激中的作用及機制[D];華中科技大學;2013年
9 趙敏;高脂飲食對大鼠肝臟內(nèi)質(zhì)網(wǎng)應激和炎癥的影響及低脂膳食干預效果研究[D];華中科技大學;2013年
10 李莉;腦紅蛋白對神經(jīng)元突起生長的作用及其潛在機制[D];華中科技大學;2013年
相關(guān)碩士學位論文 前10條
1 朱恩東;幽門螺桿菌感染相關(guān)miR-30b在胃癌發(fā)生中的功能研究[D];第三軍醫(yī)大學;2011年
2 葉敏;miRNAs在胃癌中的差異表達[D];廣州醫(yī)學院;2010年
3 唐儀;二烯丙基二硫抑制人胃低分化腺癌增殖的轉(zhuǎn)錄組學研究[D];南華大學;2010年
4 趙達;鼠傷寒沙門氏菌鞭毛蛋白對牛金黃色葡萄球菌GapC蛋白的免疫增強作用[D];黑龍江八一農(nóng)墾大學;2013年
5 楊麗敏;腦源性神經(jīng)營養(yǎng)因子Val66Met基因多態(tài)性與中國漢族精神分裂癥認知功能的相關(guān)性研究[D];山東大學;2013年
6 張惠莉;骨髓間充質(zhì)干細胞移植改善慢性腦缺血大鼠空間學習記憶能力并影響B(tài)DNF及P75NTR表達[D];鄭州大學;2013年
7 楊穎珂;骨髓間充質(zhì)干細胞移植對腦出血大鼠血腫周圍凋亡及P75NTR、TrkA表達的影響[D];鄭州大學;2013年
8 劉曉東;GDC-0941誘導人食管癌EC9706細胞凋亡及相關(guān)機制的研究[D];鄭州大學;2013年
9 徐漢陽;擬南芥EFR與黑腹果蠅SCOT蛋白重組表達、純化及晶體研究[D];安徽大學;2013年
10 王志明;FBXW7和Ki-67在人腦膠質(zhì)瘤中的表達及臨床意義[D];河北醫(yī)科大學;2013年
，本文編號：2176573
本文鏈接：http://www.sikaile.net/yixuelunwen/shenjingyixue/2176573.html
最近更新
教材專著
