本文關(guān)鍵詞：出生前后慢性鋁暴露對年輕大鼠海馬LTP及nNOS、NO、Ng的影響　出處：《中國醫(yī)科大學》2008年碩士論文　論文類型：學位論文

  更多相關(guān)文章： 出生前后鋁暴露 學習和記憶 長時稱增強 神經(jīng)型一氧化氮合酶 一氧化氮 神經(jīng)顆粒素 電鏡

【摘要】： 前言 鋁(aluminum)是地殼中含量最豐富的元素之一,大量蓄積可產(chǎn)生神經(jīng)毒性作用。國內(nèi)外流行病學調(diào)查和研究表明,鋁易致神經(jīng)元損傷,引起智力和認知能力下降等學習和記憶方面的缺陷。目前動物實驗已證實,鋁暴露可致大鼠癡呆,其不僅表現(xiàn)為學習和記憶的行為障礙,而且其病理形態(tài)學改變也與阿爾茨海默病(AD)相似。 海馬是學習和記憶的關(guān)鍵腦區(qū),海馬長時程增強(long-term potentiation,LTP)是NMDA受體依賴性突觸傳遞效能的持續(xù)性增強,是公認的腦學習記憶功能在突觸水平的研究模型和神經(jīng)基礎(chǔ)。因此研究鋁暴露對海馬LTP及與其突觸機制有關(guān)的各項生化指標的影響,有助于從突觸和蛋白分子水平闡明鋁損害腦學習和記憶功能的作用機制。目前雖然鋁對LTP損害作用的觀察很多,但其損害作用的突觸機制尚未完全闡明。 母體期和斷乳后發(fā)育期是腦發(fā)育和逐漸完善的重要階段,有關(guān)此階段鋁對學習和記憶及LTP影響的報道很少,因此我們應(yīng)該對鋁的潛在發(fā)育毒性及直接發(fā)育毒性給予特別關(guān)注。且文獻檢索顯示,鋁對NO的直接影響尚未見報道。 本實驗以出生前后(包括母體期和斷乳后發(fā)育期)慢性鋁暴露為模型,觀察鋁對母體期腦發(fā)育的間接發(fā)育毒性和斷乳后腦發(fā)育期的直接發(fā)育毒性所致學習和記憶能力、LTP誘導(dǎo)與維持的改變及對海馬細胞內(nèi)nNOS、NO、Ng的影響,進一步探討鋁對學習與記憶的影響及其突觸機制,為鋁所致兒童智力和認知能力低下性神經(jīng)疾病的早期防治提供重要的實驗依據(jù)。 材料與方法 1、動物分組與染毒 健康Wistar大鼠45只(由中國醫(yī)科大學實驗動物中心提供),體重300g左右,♀♂2:1。適應(yīng)飼養(yǎng)環(huán)境1 wk后按體重隨機分為3組:對照組、低劑量組和高劑量組,每組15只(♀♂2:1)。對照組(control group):飲用蒸餾水;低劑量組(0.2%-Al group):飲用含0.2%AlCl_3的蒸餾水溶液;高劑量組(0.4%-Al group):飲用含0.4%AlCl_3的蒸餾水溶液。各組自染毒始即分別合籠,子代鼠出生后通過母乳繼續(xù)染毒,出生后21 d斷乳,斷乳后各組子代鼠對應(yīng)分別以蒸餾水或母鼠染毒劑量的AlCl_3溶液喂養(yǎng),至子鼠生后90 d。然后按原母鼠染毒的劑量分組,每窩取1～2只子鼠(♀♂各半),組成子代各實驗組,各項實驗每組7～13只,撤毒后以蒸餾水喂養(yǎng)。各組分批交替進行各項測試實驗。動物室溫度18℃～23℃,相對濕度45%～55%,光照時間12h:12h。 2、腦組織及血液中鋁含量測定 準確稱取(0.1～0.5)g的腦組織或準確吸取(0.2-0.5)ml的全血于石英燒杯中,加(5～8)ml混酸,同時做空白對照。采用原子吸收石墨爐法測定腦鋁和血鋁含量。 3、學習與記憶的行為學測定 測試方法為跳臺法(即步下試驗)。學習行為訓練:將大鼠放入跳臺儀內(nèi)適應(yīng)3 min后訓練其找到平臺三次,大鼠跳下平臺時,立即通電給予持續(xù)電刺激(36 V)并開始計時,記錄5 min內(nèi)大鼠受到電刺激第一次跳上平臺躲避電擊的反應(yīng)時間(escape latency,EL)以及受到電擊的次數(shù)(number of errors)。24 h后進行記憶保持測試:記錄大鼠置于平臺到第1次跳下平臺的時間(step-down latency,SDL)和5 min內(nèi)受到電擊的次數(shù)(錯誤次數(shù))。 4、電生理LTP測定 烏拉坦麻醉后,將動物頭部固定于腦立體定位儀上,暴露顱骨。將雙極刺激電極插入右側(cè)海馬CA3區(qū)錐體細胞發(fā)出的Schaffer側(cè)枝部位(坐標:前囟后3.3mm;旁開3.8 mm;皮層下3.8 mm),將內(nèi)充3 mol/L的記錄玻璃微電極插入海馬CA1區(qū)部位(坐標:前囟后3.3 mm;旁開1.5 mm;電極尖端抵皮層表面),然后逐步推進行細胞外記錄。先找到穩(wěn)定的群體鋒電位(population spike,PS)后,首先記錄30 min每分鐘單脈沖刺激所誘發(fā)的PS。然后觀察給予同樣強度及波寬的的短串高頻條件刺激(100 HZ、持續(xù)5s)后,記錄45 min每分鐘給一個單脈沖檢驗刺激所誘發(fā)的PS的幅值變化。 5、nNOS表達的測定 電生理測試后的大鼠,4%多聚甲醛固定液心臟灌流固定。常規(guī)石蠟切片制作,用免疫組織化學的方法測定海馬nNOS表達。用Metamorph/Evolution/BX51顯微圖像分析系統(tǒng)進行圖像分析。 6、NO含量的測定 采用硝酸還原酶法。電生理測試后的大鼠,迅速斷頭取腦,在冰盤上快速剖取海馬,電子天平準確稱重后加入9倍冷生理鹽水,按試劑盒說明進行操作。 7、Ng表達的測定 電生理測試后的大鼠,迅速斷頭取腦,在冰盤上快速剖取海馬,按體積比為1:6～1:9放到預(yù)冷的裂解緩沖液中。4℃超聲粉碎后12 000 r/min離心1 h,取上清分裝。按照常規(guī)Western blot方法分離蛋白質(zhì)。將蛋白印跡顯影圖掃描,再利用ChemiImager 5500 V 2103圖像分析軟件對實驗結(jié)果(測定目標帶灰度值)進行分析。 8、海馬形態(tài)學超微結(jié)構(gòu)觀察 取大鼠海馬用常規(guī)透射電鏡觀察出生前后慢性鋁暴露情況下年輕大鼠的神經(jīng)細胞的形態(tài)變化。 9、統(tǒng)計學處理 實驗所得數(shù)據(jù)資料用(?)±s表示,組間資料統(tǒng)計用(SPSS軟件)單因素方差分析(ANOVA)檢驗,行為學數(shù)據(jù)不服從正態(tài)分布,采用秩和檢驗。 實驗結(jié)果 1、各組大鼠血鋁和腦鋁含量的比較 隨著鋁暴露劑量的升高,鋁暴露組大鼠的血鋁、腦鋁含量逐漸升高,且均顯著高于對照組(P＜0.05或P＜0.01),兩鋁暴露組間差異也顯著(P＜0.05)。 2、各組大鼠學習和記憶行為學的改變 與對照組相比,兩鋁暴露組大鼠第一次跳上平臺的時間(反應(yīng)時間)均明顯延長(P＜0.01),跳下平臺的潛伏期明顯縮短(P＜0.01),5 min內(nèi)錯誤次數(shù)顯著增加(P＜0.01),且兩鋁暴露組間亦有顯著性差異(P＜0.01或P＜0.05)。 3、各組大鼠PS幅值變化(即LTP增強率)的比較 隨著鋁暴露劑量的升高,高頻刺激后PS幅值增強率依次降低,兩鋁暴露組與對照組相比,顯著降低(P＜0.01),但兩暴露組之間差異不顯著。 4、各組大鼠海馬nNOS表達的變化 與對照組相比,各鋁暴露組海馬CA1、CA3區(qū)nNOS表達均顯著減少,且兩暴露組組間也有極顯著性差異(P＜0.01)。 5、各組大鼠海馬細胞內(nèi)NO含量的變化 隨著鋁暴露劑量的升高,大鼠海馬細胞內(nèi)NO含量依次降低。兩鋁暴露組均明顯低于對照組(P＜0.01),且兩暴露組間也有極顯著性差異(P＜0.01)。 6、各組大鼠海馬細胞內(nèi)Ng表達的變化 隨著染鋁濃度的增加,Ng表達量降低。與對照組相比,各染毒組海馬胞內(nèi)Ng含量均顯著降低,但兩鋁暴露組組間差異不顯著。 7、各組大鼠海馬形態(tài)學超微結(jié)構(gòu)觀察 與對照組相比,兩鋁暴露組海馬神經(jīng)元受到損傷,細胞膜和細胞質(zhì)溶解,核破損,細胞器破壞。 討論 母體期和斷乳后發(fā)育期腦的功能受損的研究是一個關(guān)系到嬰幼兒智力健康發(fā)育的重要問題,同時,研究鋁對此階段腦發(fā)育的影響及其機制,對預(yù)防鋁所致神經(jīng)性疾病有著重要意義。本實驗觀察到,出生前后慢性鋁暴露(孕期、哺乳期和斷乳后發(fā)育期)的各組年輕大鼠腦鋁及血鋁含量均顯著升高。與對照組相比,兩鋁暴露組的學習和記憶能力及LTP誘導(dǎo)與維持均明顯下降,表明出生前后的鋁暴露,可通過胎盤和血腦屏障進入子代大鼠體內(nèi),造成鋁在子代體內(nèi)蓄積,特別是腦內(nèi)的蓄積,進而損害了子代鼠的學習和記憶能力。本實驗還觀察到,各組海馬細胞內(nèi)nNOS、Ng表達及NO含量也明顯降低,提示,出生前后連續(xù)慢性鋁暴露年輕大鼠學習記憶能力減退的可能原因之一是鋁干擾了nNOS的表達,進一步抑制了NO的生成。另一原因可能是鋁抑制了Ng的表達。 就我們所涉獵的文獻顯示,鋁可干擾谷氨酸能神經(jīng)傳遞、NMDA受體相關(guān)的信號轉(zhuǎn)導(dǎo)途徑,鋁可抑制參與胞內(nèi)鈣信號調(diào)節(jié)的多種分子途徑,鋁可降低小腦內(nèi)鈣調(diào)蛋白(CaM)的含量,鋁還可使膽堿能和去甲腎上腺素能神經(jīng)傳遞發(fā)生改變�？梢�,鋁損傷了LTP誘導(dǎo)中的一系列環(huán)節(jié),使Glu、NMDA受體、Ca~(2+)與CaM均減少,必然影響其下游過程。 Ca~(2+)/CaM可激活nNOS,鋁可抑制nNOS的表達,也可通過降低Ca~(2+)濃度及CaM使nNOS激活減少,從而使NO生成減少。此外,Ng是CaM的儲庫,鋁可抑制Ng的表達。通過上述途徑導(dǎo)致LTP的誘導(dǎo)和維持受阻,致使大鼠學習和記憶能力下降。 鋁能夠引起線粒體和DNA的損傷進而導(dǎo)致神經(jīng)元細胞的損傷和凋亡。 總之,鋁可損害LTP誘導(dǎo)中的多種突觸機制,從而損害大鼠的學習和記憶能力。 結(jié)論 (1)出生前后慢性鋁暴露使大鼠學習測試的反應(yīng)時間顯著延長,記憶測試的潛伏期明顯縮短,5 min錯誤次數(shù)均顯著增加,提示鋁暴露損害了大鼠的學習和記憶行為。 (2)出生前后慢性鋁暴露使PS幅值增強率減小,提示該暴露損害了大鼠LTP的誘導(dǎo)與維持。 (3)出生前后慢性鋁暴露使海馬細胞內(nèi)nNOS表達減少,進而使NO含量顯著降低,提示這可能是鋁損害LTP的另一突觸機制。 (4)出生前后慢性鋁暴露使海馬細胞內(nèi)Ng表達減少,可能是鋁損害LTP的機制之一。 (5)出生前后慢性鋁暴露使腦組織的結(jié)構(gòu)和細胞形態(tài)發(fā)生改變,提示鋁損害了細胞功能狀態(tài)可能是鋁損害學習記憶的機制之一。
[Abstract]:Preface
Aluminum (aluminum) is one of the most abundant elements in the earth, a large number of stock can produce neurotoxic effects. The epidemiological investigation and study showed that Al can impair neuronal damage, cause mental and cognitive decline of learning and memory defects. The animal experiments have confirmed that aluminum exposure can cause dementia rats, which shows for behavioral disorders of learning and memory, and the pathological change and Blzheimer disease (AD).
The hippocampus is the key brain area for learning and memory, hippocampal long term potentiation (long-term potentiation LTP) is NMDA receptor dependent persistent enhancement of synaptic transmission efficiency, is recognized in the study of brain function of learning and memory at the synaptic level model and neural basis. So the research of aluminum exposure effects on the biochemical indicators of the hippocampus LTP and its synaptic mechanism, helps to elucidate the mechanism of aluminum damage brain function of learning and memory from the level of synapse and protein molecules. Although many effects of aluminum on LTP damage, but the damage of synaptic mechanism has not been fully elucidated.
Maternal and postweaning period is an important stage of brain development and gradually perfect, the effect of this stage of aluminum on learning and memory and LTP are seldom reported, so we should potential developmental toxicity and developmental toxicity of aluminum is directly given special attention. And literature retrieval shows that the direct effect of aluminum on NO has not been reported.
In this experiment, before and after birth (including the development of maternal and postweaning chronic aluminum exposure) as a model, the direct developmental toxicity caused by the ability of learning and memory were aluminum on brain development of maternal indirect developmental toxicity and weaning hindbrain development period, and maintain the change and nNOS of sea horse cells induced by LTP NO, Ng the influence to further explore the influence of aluminum on learning and memory and synaptic mechanisms, provide an important experimental basis for early prevention and treatment of mental and cognitive ability of children of low aluminum induced nerve disease.
Materials and methods
1, animal grouping and poisoning
45 healthy Wistar rats (provided by the experimental animal center of China Medical University), weighing about 300g, female male 2:1. adapt to rearing environment after 1 wk were randomly divided into 3 groups: control group, low dose group and high dose group, 15 rats in each group (female male 2:1). The control group (control group): drinking distilled water; low dose group (0.2%-Al group): distilled water drinking water containing 0.2%AlCl_3 solution; high dose group (0.4%-Al group): distilled water drinking water containing 0.4%AlCl_3 solution. Since the beginning of the exposure group were caged offspring rats after birth through breast milk exposure continued, born 21 d after weaning, weaning after the corresponding each offspring rats respectively with AlCl_3 solution or distilled water were fed the dose to 90 D. after birth, offspring and maternal exposure to the original packet according to the dose, 1~2 offspring per litter (female male half), composed of offspring in each experimental group, the experimental group with 7~13 rats in each group, after the withdrawal of drugs with distilled water feeding The test experiments were carried out alternately in each group. The temperature of the animal room was 18 to 23, the relative humidity was 45% to 55%, and the light time was 12h:12h.
2, determination of aluminum content in brain tissue and blood
The brain tissues of (0.1 to 0.5) g were accurately selected, and the whole blood of (0.2-0.5) ml was extracted accurately in the quartz beaker, plus (5~8) ml mixed acid, while blank control was performed. Atomic absorption graphite furnace method was used to determine the content of aluminum and aluminum in brain.
3, behavioural determination of learning and memory
Test method for step-down test (i.e. step test). Learning behavior training: the rats in step-down test after 3 min training to adapt to find the three platform, the rat jumped off the platform, electricity immediately given continuous electrical stimulation (36 V) and the beginning of time, rats were recorded within 5 min by electricity the reaction time of stimulating the first jump onto the platform to avoid electric shock (escape latency, EL) and the number of shocks (number of errors).24 memory test H: after rats were recorded on the platform to the first platform jump time (step-down latency, SDL) and the number of electric shocks by 5 min (the number of errors).
4, electrophysiological LTP determination
Urethane anesthesia, the head of the animal was fixed in a stereotaxic instrument, exposing the skull. Bipolar stimulating electrode was inserted into the Schaffer site of a branch of CA3 pyramidal neurons in hippocampus of the right (coordinates: anterior fontanel 3.3mm; 3.8 mm lateral cortex; 3.8 mm, 3 mol/L) filled glass microelectrode record the insertion site in CA1 region of hippocampus (coordinates: anterior fontanelle after 3.3 mm; 1.5 mm lateral; the electrode tip against the cortical surface), and then gradually push for extracellular recording. To find a stable population spike (population spike, PS), the first recorded 30 min per minute single pulse stimulation induced by PS. and observed given the same strength and the duration of the short on condition of high frequency stimulation (100 HZ, 5S), recorded 45 min per minute to the change of the amplitude of a single pulse induced by PS stimulation test.
5, determination of nNOS expression
After electrophysiological tests, 4% paraformaldehyde fixed solution was perfused into the heart. Routine paraffin sections were made. The expression of nNOS in hippocampus was detected by immunohistochemical method. Image analysis system was performed by Metamorph/Evolution/BX51 microscopic image analysis system.
6, determination of NO content
After the electrophysiological tests, the rats were quickly decapitated, and the hippocampus was rapidly dissected on the ice tray. After weighing the electronic balance accurately, 9 times cold physiological saline was added to it, and the operation was carried out according to the kit.
7, determination of Ng expression
Rats after electrophysiological testing, quickly decapitated, hippocampus quickly split in the ice tray, according to the volume ratio of 1:6 to 1:9 in lysis buffer pre cooling.4 C ultrasonic pulverization after 12000 r/min centrifugation for 1 h, the supernatant of packaging. According to the conventional Western blot method for the isolation of protein. Protein blotting the developing map scanning, using ChemiImager V 5500 analysis software on the experimental results of 2103 images (determination of target band gray value) were analyzed.
8, ultrastructural observation of hippocampal morphology
The morphologic changes of the nerve cells in the young rats were observed with conventional transmission electron microscopy (TEM) before and after the exposure to chronic aluminum exposure.
9, statistical treatment
The experimental data were expressed by (+) s. The data between groups were statistically analyzed by single factor analysis of variance (ANOVA) with SPSS software. Behavioral data did not obey normal distribution, and rank sum test was used.
experimental result
1, comparison of blood aluminum and brain Al content in rats of each group
With the increase of aluminum exposure dose, the contents of Al and Na in the aluminum exposed group increased gradually, and all were significantly higher than those in the control group (P < 0.05 or P < 0.01), and the difference between the two aluminum exposed groups was also significant (P < 0.05).
2, changes in learning and memory behavior of rats in each group
Compared with the control group, two aluminum exposure rats first jumped on the platform of the time (reaction time) were significantly prolonged (P < 0.01), jumped off the platform was significantly shortened (P < 0.01), 5 min in the number of errors increased significantly (P < 0.01), and the two groups were exposed to aluminum there is significant difference (P < 0.01 or P < 0.05).
3, comparison of PS amplitude change (LTP enhancement rate) in rats of each group
With the increase of aluminum exposure dose, the amplitude of PS amplitudes decreased after high frequency stimulation. The two aluminum exposure group was significantly lower than the control group (P < 0.01), but the difference between two exposure groups was not significant.
4, changes in the expression of nNOS in the hippocampus of rats in each group
Compared with the control group, the expression of nNOS in CA1 and CA3 areas in the hippocampus of all aluminum exposed groups decreased significantly, and there was also significant difference between the two exposed groups (P < 0.01).
5, the changes of NO content in the hippocampal cells of rats in each group
With the increase of aluminum exposure dose, the content of NO in hippocampus cells in turn decreased. The two aluminum exposed group was significantly lower than that of the control group (P < 0.01), and there was a significant difference between the two exposed groups (P < 0.01).
6, changes in the expression of Ng in the hippocampal cells of rats in each group
As the concentration of aluminum increased, the expression of Ng decreased. Compared with the control group, the Ng content in hippocampus of each exposure group was significantly reduced, but the difference between the two aluminum exposure group was not significant.
7, ultrastructural observation of hippocampal morphology in rats of each group
Compared with the control group, the hippocampal neurons in the two aluminum exposure group were damaged, the cell membrane and cytoplasm dissolve, the nucleus was damaged, and the organelles were destroyed.
discuss
Study on brain development of maternal and postweaning impairment is vital to the healthy growth of infants and young children, at the same time, influence of aluminum in stage of brain development and its mechanism, has important significance to the prevention of aluminum induced neurological diseases. This study observed that before and after birth (pregnancy, chronic aluminum exposure lactation and postweaning period) groups of young rat brain blood aluminum and aluminum content increased significantly. Compared with the control group, two of aluminum exposure on learning and memory ability and LTP group in the induction and maintenance were significantly decreased, that of aluminum exposure before and after birth, can enter offspring rats through the placenta and blood brain barrier, resulting in the aluminum accumulation in the offspring, especially the accumulation in the brain that impairs learning and memory ability of offspring rats. This experiment also observed hippocampal cells in each group nNOS, Ng expression and NO content was significantly decreased, suggesting that, One of the possible reasons for the decrease in learning and memory ability of young rats is that aluminum interferes with the expression of nNOS and further inhibits the generation of NO. Another reason is that aluminum inhibits the expression of Ng.
We read of the literature shows that aluminum can interfere with the transmission of glutamate and NMDA receptor signal transduction pathway is involved in a variety of aluminum can inhibit the molecular regulation of intracellular calcium signaling pathway, aluminum can reduce the brain calmodulin (CaM) content of aluminum can also make the cholinergic and noradrenergic neurotransmission occurs change. Obviously, LTP induced damage of aluminum in a series of links, Glu, NMDA receptor, Ca~ (2+) and CaM were reduced, will inevitably affect the downstream process.
Ca~ (2+) /CaM can activate nNOS, the expression of aluminum can inhibit nNOS, also can reduce Ca~ (2+) concentration and CaM nNOS is activated to reduce, thereby reducing NO production. In addition, Ng is the storage of CaM, the expression of Al inhibited Ng. By the way leads to the induction and maintenance of blocked LTP, resulting in the decrease of learning and memory ability in rats.
Aluminum can cause damage to mitochondria and DNA and lead to neuronal cell damage and apoptosis.
In conclusion, aluminum can damage a variety of synaptic mechanisms induced by LTP, thereby damaging the learning and memory ability of rats.
conclusion
(1) chronic aluminum exposure before and after birth significantly increased the response time of learning test, significantly shortened the latency of memory test, and significantly increased the number of erroneous errors at 5 min, suggesting that aluminum exposure impairs learning and memory behavior in rats.
(2) chronic aluminum exposure before and after birth reduced the PS amplitude enhancement rate, suggesting that the exposure damage the induction and maintenance of LTP in rats.
(3) chronic aluminum exposure before and after birth reduced the expression of nNOS in the hippocampal cells and reduced the content of NO significantly, suggesting that this may be another synaptic mechanism of aluminum damage to LTP.
(4) chronic aluminum exposure before and after birth reduces the expression of Ng in the hippocampal cells, which may be one of the mechanisms of aluminum damage to LTP.
(5) the chronic aluminum exposure before and after birth has changed the structure and cell morphology of the brain, suggesting that aluminum damages the functional state of cells, which may be one of the mechanisms that aluminum damages learning and memory.

【學位授予單位】：中國醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2008
【分類號】：R363;R749.16

【參考文獻】

相關(guān)期刊論文 前10條

1 王曉波,孔繁增;鋁對人體健康研究新進展[J];環(huán)境與健康雜志;1997年04期

2 邱幸凡;袁德培;王平;張六通;;醒腦益智方對老年性癡呆模型大鼠大腦皮質(zhì)及海馬區(qū)nNOS表達的影響[J];河南中醫(yī);2006年04期

3 柳剛,陳麗,冉祥凱,韓杰,鄭冬梅,陳青,牟忠卿,白秀燕;NOS在糖尿病大鼠海馬中的表達及其與認知功能的關(guān)系[J];山東大學學報(醫(yī)學版);2003年02期

4 殷盛明;于德欽;彭巖;高溪;趙杰;唐一源;張萬琴;;蝎毒耐熱蛋白保護MPTP小鼠空間學習記憶障礙的一氧化氮機制[J];神經(jīng)解剖學雜志;2006年01期

5 張蔚婷,羅非,韓濟生;更聰明的小鼠!?[J];生理科學進展;1999年04期

6 楊永堅,胡浩,李小平,王取南;亞慢性鋁暴露致小鼠腦神經(jīng)細胞DNA損傷[J];中國工業(yè)醫(yī)學雜志;2005年03期

7 肖林,程雅琴;檢測人血白蛋白中鋁含量的石墨爐原子吸收分光光度法的建立[J];中國生物制品學雜志;2001年03期

8 李云濤,晉光榮,徐漢榮,劉俊華,陸澄;局灶性腦缺血大鼠學習記憶能力與海馬齒狀回nNOS表達的關(guān)系[J];現(xiàn)代醫(yī)學;2005年03期

9 謝寧,柳琳,周妍妍,何秀麗,鄒純樸;地黃飲子對老年性癡呆模型大鼠腦組織NO、NOS含量及行為學的影響[J];中國中醫(yī)藥科技;2004年02期

10 王林平;牛僑;陳藝蘭;張勤麗;劉慧君;高茂龍;王靜;;鋁對大鼠海馬神經(jīng)細胞線粒體酶的影響[J];毒理學雜志;2005年04期

，

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