發(fā)布時(shí)間：2018-06-25 01:32

  本文選題：垂體切除 + 神經(jīng)發(fā)生�。� 參考：《南方醫(yī)科大學(xué)》2015年碩士論文

【摘要】：研究背景：哺乳動(dòng)物的下丘腦神經(jīng)垂體束(Hypothalamo-neurohypophyseal Tract)由下丘腦室旁核(Paraventricular hypothalamic Nucleus,PVN)和視上核(Supraoptic Nucleus,SON)大細(xì)胞神經(jīng)元發(fā)出的神經(jīng)軸突形成,軸突延伸至垂體后葉,主要有合成、轉(zhuǎn)運(yùn)和釋放大細(xì)胞神經(jīng)元分泌的精氨酸加壓素(Arginine Vasporessin, AVP)和催產(chǎn)素(Oxytocin, OT)的功能。而缺乏精氨酸加壓素則會(huì)出現(xiàn)尿量增多、尿比重減少、多飲等癥狀。下丘腦神經(jīng)垂體系統(tǒng)的垂體束損傷方式可以通過(guò)切除垂體來(lái)達(dá)到造模目的,常用的手術(shù)入路有咽旁入路和經(jīng)耳入路,而咽旁入路因?yàn)閷?duì)動(dòng)物損傷大,術(shù)后并發(fā)癥多,術(shù)后長(zhǎng)期存活率較低的缺點(diǎn),不適合長(zhǎng)期觀察實(shí)驗(yàn),所以擬使用經(jīng)耳入路,而立體定向下經(jīng)耳入路為方便快捷的造模方法,術(shù)后恢復(fù)快,存活率較高,但是也具有不能全切除垂體和造模率低的缺點(diǎn),而同時(shí)也有對(duì)動(dòng)物大小有限制,為了穩(wěn)定造模成功率,迫切需要探求適合手術(shù)的動(dòng)物。垂體切除術(shù)后的一系列復(fù)雜的病理生理改變?nèi)匀恍枰粩嗟奶剿?不少學(xué)者認(rèn)為是由于下丘腦神經(jīng)垂體系統(tǒng)(Hypothalamo-neurohypophyseal System,HNS)損傷后,導(dǎo)致下丘腦的大細(xì)胞神經(jīng)元的逆行性退變,最終因?yàn)榉置诩に販p少產(chǎn)生中樞性尿崩癥。同時(shí)也有不少研究提示中樞神經(jīng)系統(tǒng)的損傷可能伴隨新生細(xì)胞,而部分新生細(xì)胞通過(guò)一段時(shí)間的生長(zhǎng)后會(huì)分化并成熟為神經(jīng)元,并具有神經(jīng)元表達(dá)的蛋白和功能。然而并未確切報(bào)道證實(shí)垂體切除模型中下丘腦室旁核或視上核是否有神經(jīng)發(fā)生,而新生細(xì)胞是否并具有釋放激素功能以及新生神經(jīng)元與中樞性尿崩癥的關(guān)系進(jìn)行進(jìn)一步闡述。神經(jīng)發(fā)生為神經(jīng)前體細(xì)胞產(chǎn)生具有功能的神經(jīng)元的一個(gè)過(guò)程,近幾十年來(lái)越來(lái)越多的證據(jù)表明成年哺乳動(dòng)物腦中存在神經(jīng)干細(xì)胞,能增值和分化為新的神經(jīng)元,具有功能性并整合到成年中樞神經(jīng)系統(tǒng)中,成年動(dòng)物腦內(nèi)存在神經(jīng)干細(xì)胞的意義尚不太清楚,可能與其通過(guò)不斷的自我更新、遷移和分化來(lái)補(bǔ)充因疾病、損傷或凋亡而丟失的神經(jīng)細(xì)胞,以維持腦功能的可塑性有關(guān)。現(xiàn)在普遍認(rèn)為至少在兩個(gè)腦區(qū)存在神經(jīng)發(fā)生,即側(cè)腦室的室管膜下區(qū)(Subventricular Zone, SVZ)和海馬齒狀回的顆粒下層(Subgranular Zone,SGZ)。另外在黑質(zhì)、杏仁核、皮層、紋狀體等區(qū)域均有散在的神經(jīng)發(fā)生。而最近的研究發(fā)現(xiàn)在下丘腦也可能存在神經(jīng)發(fā)生。由此,我們推想在去垂體大鼠模型中,神經(jīng)元的逆行性退變是否會(huì)同時(shí)引起同類(lèi)神經(jīng)元的重新補(bǔ)充,其新生神經(jīng)元的起源位置是否在下丘腦附近,是否與中樞性尿崩癥有關(guān)仍待研究證實(shí)。探索闡明垂體切除術(shù)后是否有神經(jīng)發(fā)生,對(duì)神經(jīng)修復(fù)的研究有重要意義,也對(duì)以后的臨床治療提供新的思路�；谝陨峡紤],我們通過(guò)使用立體定向儀行大鼠垂體切除術(shù),并描述對(duì)術(shù)后大鼠的中樞性尿崩的規(guī)律,找到適合觀察的時(shí)間點(diǎn),同時(shí)利用新生細(xì)胞標(biāo)記方法,追蹤觀察術(shù)后大鼠下丘腦內(nèi)視上核與室旁核是否存在新生細(xì)胞,以及對(duì)新生細(xì)胞進(jìn)行定性,探討神經(jīng)發(fā)生在垂體切除模型中的規(guī)律。研究目的：1.使用立體定向儀去除不同體重范圍的大鼠垂體,以建立穩(wěn)定的立體定向去垂體大鼠模型,并觀察術(shù)后中樞性尿崩的變化特征,尋找適宜觀察神經(jīng)發(fā)生的時(shí)間窗；2.在不同時(shí)間段觀察大鼠去垂體術(shù)后下丘腦視上核、室旁核區(qū)域是否出現(xiàn)神經(jīng)發(fā)生,并觀察其成熟及存活情況；材料與方法：第一部分立體定向下大鼠垂體切除術(shù)模型及中樞性尿崩的觀察1.造模方法：利用立體定向儀經(jīng)耳入路行大鼠垂體切除。2.實(shí)驗(yàn)分組：實(shí)驗(yàn)一：雄性SD大鼠共60只,體重150-200g15只,200-250g15只,250-300g15只,300-450g15只。實(shí)驗(yàn)二：選用150-250g大鼠,垂體切除組12只,假手術(shù)組10只；3.記錄術(shù)后3天內(nèi)出現(xiàn)尿崩的大鼠數(shù)量,以術(shù)后尿量大于空手術(shù)組的2倍,尿色清亮為標(biāo)準(zhǔn),統(tǒng)計(jì)比較各組術(shù)后尿崩的發(fā)生率；4.記錄各組術(shù)后短期存活天數(shù)(5天)以及長(zhǎng)期存活天數(shù)(30天)大鼠數(shù)量,統(tǒng)計(jì)比較各組術(shù)后短期長(zhǎng)期存活率；5.術(shù)后解剖觀察垂體窩是否有殘存,統(tǒng)計(jì)各組立體定向下的全切率；6.術(shù)后測(cè)定大鼠的中樞性尿崩癥的生物學(xué)特性的變化：每日測(cè)尿量、尿比重、攝水量,并繪制尿崩曲線；7.數(shù)據(jù)處理：用SPSS20.0作統(tǒng)計(jì)學(xué)處理,數(shù)據(jù)用均數(shù)±標(biāo)準(zhǔn)差表示,采用卡方檢驗(yàn)、方差分析、重復(fù)測(cè)量數(shù)據(jù)方差分析以及各時(shí)間點(diǎn)單獨(dú)效應(yīng)的比較(LSD方法),以P0.05表示有顯著性差異。第二部分大鼠去垂體術(shù)后不同時(shí)期下丘腦新生AVP神經(jīng)元的情況1.造模及分組：造模跟第一部分一致,分組：雄性SD大鼠18只,隨機(jī)分為空手術(shù)組6只,術(shù)后10天組6只,術(shù)后20天組6只。2.BrdU標(biāo)記：術(shù)后每只大鼠每天每次腹腔注射100mg/kg的BrdU,連續(xù)7天；3. 灌注取腦及免疫熒光檢測(cè)：假手術(shù)組和垂體切除術(shù)后10天組于第10天灌注處死、20天組于術(shù)后第20天灌注處死,用生理鹽水和冰凍4%多聚甲醛心尖灌注取腦后,進(jìn)行蔗糖梯度脫水,腦組織沉底后,用冰凍切片包埋劑包埋,連續(xù)切冠狀位片,做成漂片放置4度冰箱保存。視上核與室旁核BrdU染色：漂洗腦片后經(jīng)鹽酸酸化和四硼酸鈉中和,用5%BSA室溫封閉2h,用小鼠抗BrdU抗體1：800孵育,4度過(guò)夜,漂洗后用熒光二抗488避光孵育,隔日避光PBS-T漂洗,避光孵育DAPI,滴防熒光淬滅劑熒光顯微鏡下觀察。BrdU/AVP免疫共染色：漂洗后用5%BSA封閉,用兔抗AVP抗體1：2000孵育,4度過(guò)夜,漂洗后用熒光二抗546避光孵育,避光孵育DAPI后用甲醇固定,漂洗后經(jīng)鹽酸酸化和四硼酸鈉中和后,用小鼠抗BrdU抗體1：800孵育,4度過(guò)夜,漂洗后用熒光二抗488避光孵育,滴防熒光淬滅劑熒光顯微鏡下觀察.4. 熒光顯微鏡下各組取6張間隔腦片拍照,并計(jì)數(shù)各組BrdU陽(yáng)性細(xì)胞數(shù)、AVP陽(yáng)性細(xì)胞數(shù)、BrdU與AVP共同陽(yáng)性表達(dá)細(xì)胞數(shù)。5.數(shù)據(jù)處理：用SPSS20.0作統(tǒng)計(jì)學(xué)處理,數(shù)據(jù)用均數(shù)±標(biāo)準(zhǔn)差表示,采用卡方檢驗(yàn)、方差分析,以P0.05表示有顯著性差異。結(jié)果：1.立體定向下經(jīng)耳行大鼠垂體切除術(shù),術(shù)后各組短期(5天)存活率和長(zhǎng)期(30天)存活率各組之間無(wú)明顯差異。各組尿崩發(fā)生率、全切除率無(wú)統(tǒng)計(jì)學(xué)差異。2.立體定向大鼠垂體切除術(shù)后出現(xiàn)中樞性尿崩,經(jīng)統(tǒng)計(jì)檢驗(yàn)?zāi)虮罃?shù)據(jù)可劃分為小于47.5ml/24h與高于47.5ml/24h兩個(gè)范圍,將波動(dòng)趨勢(shì)曲線被劃分為3部分,分別為術(shù)后第1天至第6天、第7天至第11天、第12天至20天。呈三相型尿崩。術(shù)后第1天到第6天為急性期,尿量、攝水量急劇升高、尿比重下降,此期尿量均值為56.4±18.9m1/24h,攝水量為63.9±27.5ml/24h,緊接著會(huì)出現(xiàn)1天或數(shù)天尿量、攝水量下降、尿比重上升的間歇期尿量、攝水量分別為40.8±12.3ml/24h,57.2±31.2ml/24h,之后尿量、攝水量重新上升,然后緩慢下降維持到一定水平的持續(xù)期,尿量、攝水量均值分別為61.1±16.5ml,63.6±30.2ml/24h,而尿比重反復(fù)波動(dòng),急性期降至1.018±0.109、間歇期1.026±0.008與空手術(shù)組無(wú)明顯差異、持續(xù)期為1.019±0.11。3.術(shù)后10天、20天觀察到大鼠下丘腦視上核與室旁核內(nèi)出現(xiàn)新生細(xì)胞,以視上核區(qū)域出現(xiàn)較多。10天組視上核的BrdU陽(yáng)性細(xì)胞數(shù)為552.7±247.9個(gè)對(duì)比20天(449.5±217.3個(gè))無(wú)明顯統(tǒng)計(jì)學(xué)差,10天組的BrdU陽(yáng)性細(xì)胞數(shù)為117.6±66.2個(gè)對(duì)比20天組63.7±45.3個(gè)也無(wú)顯著統(tǒng)計(jì)學(xué)差異。4.10天組中視上核表達(dá)AVP的BrdU為113±61.1個(gè)與20天組(130±65.8個(gè))比較無(wú)統(tǒng)計(jì)學(xué)差異。而在室旁核上,術(shù)后10天組的免疫共染雙陽(yáng)性的細(xì)胞數(shù)為34.8±27.6個(gè)對(duì)比20天組22.8±16.3個(gè)無(wú)統(tǒng)計(jì)學(xué)差異,而10天組的視上核與室旁核相比,有統(tǒng)計(jì)學(xué)意義。提示術(shù)后一段時(shí)間后視上核與室旁核的新生細(xì)胞有部分可分化成熟為為表達(dá)AVP的神經(jīng)元,以視上核區(qū)域較多,而術(shù)后20天視上核的新生AVP神經(jīng)元占總AVP神經(jīng)元比例較視上核術(shù)后10天組較大。5.10天組的6只大鼠視上核AVP陽(yáng)性細(xì)胞合計(jì)總數(shù)為11694個(gè),6只大鼠BrdU與AVP共染雙陽(yáng)性細(xì)胞總數(shù)為678個(gè),陽(yáng)性率為5.8%；20天組6只大鼠視上核陽(yáng)性細(xì)胞總數(shù)為6324個(gè),6只大鼠BrdU與AVP共染雙陽(yáng)性細(xì)胞總數(shù)為781個(gè),陽(yáng)性率為12.3%。χ2246.38,P0.01,提示20天組的視上核新生的AVP細(xì)胞占分泌AVP細(xì)胞的比例比10天組要高。而在室旁核10天組與20天組無(wú)明顯統(tǒng)計(jì)學(xué)差異。結(jié)論：1.立體定向儀輔助下行大鼠垂體切除術(shù)模型的適合體重范圍為150-400g；2.立體定向下行大鼠垂體切除術(shù)可成功模擬中樞性尿崩,其尿量、尿比重及攝水量呈三相性尿崩的規(guī)律；3.垂體切除術(shù)大鼠下丘腦視上核與室旁核在有新生細(xì)胞；視上核較室旁核多,而間歇期與持續(xù)期的新生細(xì)胞區(qū)別不大,而有下降的趨勢(shì)；4.新生的細(xì)胞經(jīng)過(guò)一段生長(zhǎng)可以分化成熟為分泌AVP神經(jīng)元,提示神經(jīng)發(fā)生可能為損傷后的另一代償反應(yīng)。
[Abstract]:Study background: the hypothalamic neurohypophysis bundle (Hypothalamo-neurohypophyseal Tract) of mammals is formed by the axons of the paraventricular paraventricular nucleus (Paraventricular hypothalamic Nucleus, PVN) and the large cell neurons of the supraventricular (Supraoptic Nucleus, SON) cells. The axons extend to the posterior pituitary, which are mainly synthesized, transported and amplified. The function of the Arginine Vasporessin (AVP) and oxytocin (Oxytocin, OT) secreted by the cell neurons. But the lack of arginine vasopressin will increase the amount of urine, decrease the proportion of urine, and drink and so on. The pituitary tract injury of the hypothalamus neurohypophysis system can be used to achieve the purpose of modeling by excising the pituitary gland. The parapharyngeal approach and through the ear approach, while the parapharyngeal approach is not suitable for long-term observation, because of the large injury to the animals, many complications after the operation and the low survival rate after the operation, so it is not suitable for the long term observation. In order to stabilize the size of the animals, there is an urgent need to explore the animals that are suitable for the operation. A series of complicated pathophysiological changes after the resection of the pituitary gland still need to be explored, and some scholars believe that the hypothalamus neurohypophysis system (Hy Pothalamo-neurohypophyseal System, HNS), after injury, causes retrograde degeneration of the large cell neurons in the hypothalamus, eventually resulting in central diabetes insipidus due to a decrease in the secretion of hormones, and many studies suggest that the damage of the central nervous system may be accompanied by new cells, and some new cells are divided for a period of time. However, there is no definite report on whether the paraventricular nucleus or supraventricular nucleus has neurogenesis in the pituitary excision model, and whether the newborn cells have the function of releasing hormone and the relationship between the newborn neurons and central diabetes insipidus. A process in which neural progenitor cells produce functional neurons. In recent decades, more and more evidence shows that there are neural stem cells in the adult mammalian brain that can add and differentiate into new neurons, which are functional and integrated into the adult central nervous system, and adult brain is in the mind of neural stem cells in the brain. It is not clear that it is possible to supplement the nerve cells lost by disease, injury or apoptosis through continuous self renewal, migration and differentiation to maintain the plasticity of brain function. It is now generally believed that at least two brain regions have neurogenesis, the Subventricular Zone, SVZ, and the dentate dentate of the lateral ventricle. Subgranular Zone, SGZ. Also in the substantia nigra, the amygdala, the cortex, the striatum, and other neurogenesis. And recent studies have found that there may be neurogenesis in the hypothalamus. Thus, we think in the pituitary rat model, whether retrograde degeneration of nerve element can cause similar neurons in the rat model. Whether or not the origin of the newborn neurons is located near the hypothalamus, whether it is related to the central diabetes insipidus remains to be studied. The stereotactic rat pituitary adenohypophysis was performed, and the rules of central diabetes insipidus in the rats were described, and the time points were found suitable for observation. At the same time, the new cells were traced and observed in the hypothalamus and paraventricular nucleus of the hypothalamus in the rats after the operation. The rule in the pituitary resection model. Objective: 1. using stereotactic apparatus to remove the rat pituitary of different weight range to establish a stable stereotactic pituitary rat model, and to observe the changes of the central diabetes insipidus after the operation, to find the time window suitable for the observation of the neurogenesis, and 2. to observe the rat pituitary surgery at different time periods. The hypothalamic supraventricular nucleus and paraventricular nucleus are neurogenesis, and their maturation and survival are observed. Materials and methods: the first part of the stereotactic rat pituitary resection model and central diabetes insipidus 1. model methods: the stereotactic approach by the ear approach to the rat pituitary resection.2. experiment group: Experiment 1: Male A total of 60 SD rats, body weight 150-200g15, 200-250g15 only, 250-300g15 only, 300-450g15 only. Experiment two: 150-250g rats, 12 pituitary excision group and 10 sham operation group; 3. the number of diabetes insipidus in 3 days after operation was recorded, the urine volume was 2 times greater than that of the empty operation group, and the urine color was clear as the standard, and the statistical comparison of postoperative diabetes insipidus was made. The number of short-term survival days (5 days) and the number of long term survival days (30 days) of rats after operation were recorded, and the short-term long-term survival rate of each group after operation was compared. The survival of the pituitary fossa was observed after 5. operation, and the total resection rate under stereotactic stereotactic in each group was observed. 6. the biological characteristics of central diabetes insipidus in rats were measured after 6. operation. Changes: daily measurement of urine volume, urine specific gravity, water intake, and mapping of diabetes insipidus; 7. data processing: statistical processing with SPSS20.0, data using mean standard deviation of mean number, chi square test, variance analysis, repeated measurements of variance analysis and the comparison of individual response at each time point (LSD method), showing significant differences in P0.05. The 1. model and grouping of the hypothalamus AVP neurons in the second part of the rat after the hypophysis operation: the model was in accordance with the first part, group: 18 male SD rats were randomly divided into 6 rats in the empty operation group, 6 rats in the 10 day group after the operation, and 6.2.BrdU markers in the group 20 days after the operation: each rat after the operation was intraperitoneally injected with BrdU of 100mg/kg a day each time each time intraperitoneal injection of 100mg/kg, each rats intraperitoneally each day, each time intraperitoneal injection of BrdU, each time abdominal injection of 100mg/kg, each rats intraperitoneally each day, each time intraperitoneal injection of BrdU, each rat, every day. 7 consecutive days; 3. perfusion of brain and immunofluorescence test: 10 days after 10 days after the sham operation group and the pituitary resection, the 20 day group was perfused at the twentieth day after the operation, and then the brain was perfused with saline and 4% POM apex, and the sucrose gradient dehydration was carried out. After the brain group was weave the bottom, the frozen section embedding agent was buried continuously and cut continuously. Coronary film, make a drifting piece to store 4 degrees fridge. Visual nucleus and paraventricular nucleus BrdU staining: after rinsing the brain slices through acidification of hydrochloric acid and four sodium borate, closed 2H at room temperature with 5%BSA room temperature, incubated with anti BrdU antibody 1:800 in mice, 4 degrees for night, after rinsing with fluorescent two against 488 light and incubating, avoiding PBS-T rinsing every other day, incubating DAPI in light of light and dropping fluorescent fluorescence The.BrdU/AVP immunofluorescence was observed under the fluorescence microscope: after rinsing with 5%BSA, the rabbit was incubated with the Rabbit anti AVP antibody 1:2000, 4 degrees were spent overnight, after rinsing, the fluorescent two was incubated with 546 anti light, and after DAPI was incubated with methanol to fix it. After rinsing, the mice were incubated with anti BrdU antibody 1:800 and 4 degrees for the night after acidification of hydrochloric acid and four of sodium borate. After rinsing after rinsing with fluorescent two anti 488 light, the fluorescence microscope was used to observe the number of 6 spaced brain slices under.4. fluorescence microscope, and count the number of BrdU positive cells in each group, the number of AVP positive cells, and the number of BrdU and AVP positive expression cells.5. data processing: SPSS20.0 for statistical processing and the data used for mean number There was significant difference between Chi square test and variance analysis by P0.05. Results: 1. stereotactic stereotactic rat pituitary excision was performed. There was no significant difference in the survival rate and the long-term (30 day) survival rate between each group after the operation. The incidence of diabetes insipidus in each group and the total resection rate were not statistically different from the.2. stereotactic rat drooping. Central diabetes insipidus occurred after body resection. The data of diabetes insipidus could be divided into two areas of less than 47.5ml/24h and higher than 47.5ml/24h by statistical test. The wave trend curve was divided into 3 parts, which were first to sixth days after operation, seventh to eleventh days, twelfth to 20 days, and three phase diabetes insipidus. The acute period was first days to sixth days after operation, urine volume and perturbation. The amount of water increased rapidly and the proportion of urine decreased. The mean urine volume was 56.4 + 18.9m1/24h, and the water intake was 63.9 27.5ml/24h. The urine volume was 1 days or several days, the water intake was decreased and the urine specific gravity was increased in the intermittent period of urine. The water intake was 40.8 + 12.3ml/24h and 57.2 + 31.2ml/ 24h respectively. Then the urine volume, the water intake rose again, and then slowly decreased. At a certain level of duration, the mean urine volume and water intake were 61.1 16.5ml and 63.6 30.2ml/24h respectively, while the urine specific gravity fluctuated repeatedly, the acute phase decreased to 1.018 + 0.109, and the intermittent period was 1.026 + 0.008 with the empty operation group. The duration was 1.019 + 0.11.3. after 10 days, and the new hypothalamic supraventricular nucleus and the hypothalamus of the rat were observed on the 20 day. The number of BrdU positive cells in the suprasiasal nucleus was 552.7 + 247.9 compared to 20 days (449.5 + 217.3), and the number of BrdU positive cells in the 10 day group was 117.6 + 66.2 compared to 20 days in 63.7 + 63.7 and no statistically difference.4.10 days, and the BrdU of AVP in the supra optic nucleus was 113 + 61.. There was no statistical difference between the 1 and the 20 day group (130 + 65.8). On the paraventricular nucleus, the number of immune co dyed double positive cells in the 10 day group was 34.8 + 27.6 compared to 20 days and 22.8 + 16.3, but the supraventricular nucleus of the optic nucleus in the 10 day group was statistically significant. The new cells could be partially differentiated and mature to express AVP, with more optic nucleus area, and the proportion of the new AVP neurons in the supra optic nucleus 20 days after the operation was 11694 in the 6 rats of the 10 day group of the larger.5.10 day group, and 6 rats with BrdU and AVP were co dyed double positive. The total number of cells was 678, the positive rate was 5.8%, the total number of positive cells of the upper nucleus of 6 rats in the 20 day group was 6324, the total number of BrdU and AVP co dyed double positive cells in 6 rats was 781, the positive rate was 12.3%. Chi 2246.38, P0.01, suggesting that the proportion of the AVP cells in the supraventricular nucleus of the 20 day group was higher than that of the 10 days group, and in the paraventricular nucleus 10 days group. There was no significant difference between the 20 days and the 20 day group. Conclusion: 1. stereotactic assisted pituitary adenohypophysis model is suitable for the body weight range of 150-400g; 2. stereotaxic pituitary adenohypophysis can successfully simulate central diabetes insipidus, and the urine volume, urine specific gravity and water uptake are three phase diabetes insipidus; 3. pituitary resection of the lower colliculus in rats There are new cells in the supraventricular nucleus and supraventricular nucleus; the supraventricular nucleus is more than the paraventricular nucleus, while the intermittent and persistent new cells are not very different and have a downward trend. 4. new cells can differentiate and mature to secrete AVP neurons after a period of growth, suggesting that neurogenesis may be another compensatory response after injury.
【學(xué)位授予單位】：南方醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類(lèi)號(hào)】：R651.1

【共引文獻(xiàn)】

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