【摘要】：[目的]探討續(xù)斷提取物對血管性癡呆大鼠學(xué)習(xí)記憶能力的影響。[方法]1.急性毒性實驗：大鼠32只,隨機分為兩組(對照組,續(xù)斷提取物組)。實驗前動物禁食不禁水16h,灌胃后禁食不禁水4h,1d內(nèi)3次灌胃,每次間隔4h,續(xù)斷提取物組給予最大濃度的續(xù)斷提取物(0.3g/ml),另一組給予同等量的蒸餾水,按大鼠最大胃容量(4ml/100g),兩次灌胃間隔4h。灌胃1d后連續(xù)觀察7d,包括兩組大鼠呼吸、進食、體毛、口鼻分泌物、體重及一般狀態(tài)。2.續(xù)斷提取物對VAD大鼠學(xué)習(xí)記憶實驗：將48只雄性SD大鼠隨機分為正常組、假手術(shù)組、模型組和續(xù)斷提取物高、中、低劑量組,每組各8只。采用反復(fù)夾閉雙側(cè)頸動脈法制作血管性癡呆模型。各給藥組給予相應(yīng)劑量(0.25g/kg、0.5g/kg、 lg/kg)續(xù)斷提取物水溶液,假手術(shù)、模型組給予等容量蒸餾水,每日一次,連續(xù)灌胃21d。利用Miorris水迷宮進行定位航行實驗和空間探索能力實驗。利用酶聯(lián)免疫法測定血清中SOD、MDA和GSH含量。[結(jié)果]1.急性毒性試驗無法測定急性毒性。最大耐受量時,連續(xù)觀察7d,大鼠運動情況、呼吸、進食、飲水、體毛、口鼻分泌物、狀態(tài)及體重均未見明顯異常,動物一般狀態(tài)良好,無異常狀態(tài)及死亡。解剖后,肉眼觀察各主要臟器無明顯異常變化。續(xù)斷提取物的最大給藥量是0.3g/ml×40ml/kg×3次=36g/kg,是成人每日續(xù)斷提取物最大常用量(16g/60kg)的135倍。2.續(xù)斷提取物對血管性癡呆大鼠學(xué)習(xí)記憶能力的影響①一般狀態(tài)：灌胃期間各組大鼠一般狀態(tài)良好,體重普遍增長,增長無明顯差異。②續(xù)斷提取物對大鼠空間記憶及空間探索能力的影響：開始兩天各組間大鼠尋找站臺潛伏期相比無統(tǒng)計學(xué)意義。從第三天開始,中、高劑量組較模型組大鼠的尋找站臺潛伏期時間明顯縮短(P0.05),撤出平臺后其穿越平臺次數(shù)較模型組明顯增多(P0.05)。③血清中SOD、MDA、GSH的影響：續(xù)斷提取物中、高劑量組大鼠血清中SOD、GSH含量增高,MDA活力降低,與模型組比較均具有統(tǒng)計學(xué)意義(P0.05)。[結(jié)論]1.對于SD大鼠,續(xù)斷提取物最大給藥量為36g/kg,是成人每日最大常用量的135倍,無明顯的藥物毒性,說明續(xù)斷提取物藥物毒性極低；2.續(xù)斷提取物能夠提高血管性癡呆大鼠的學(xué)習(xí)記憶能力,可能因其提高了大鼠血清中SOD、GSH含量,降低MDA含量。
[Abstract]:Objective: to investigate the effect of Dipsacus extract on learning and memory ability of vascular dementia rats. [methods] 1. Acute toxicity test: 32 rats were randomly divided into two groups (control group, Dipsacus extract group). Before the experiment, the animals fasted for 16 hours. After 4 hours of fasting, the animals were fed with the same amount of distilled water for 4 hours. The dipsacus extract group was given the maximum concentration of dipsacus extract (0.3g/ml), and the other group was given the same amount of distilled water, and the dipsacus extract group was given the maximum concentration of dipsacus extract (0.3g/ml). According to the maximum gastric volume (4ml/100g) of rats, the interval of gastric perfusion was 4 h. The rats in the two groups were observed continuously for 7 days, including breathing, feeding, body hair, oral and nasal secretions, body weight and general state. 2. Learning and memory experiment of Dipsacus extract on VAD rats: 48 male SD rats were randomly divided into normal group, sham operation group, model group and Dipsacus extract high, middle and low dose groups, with 8 rats in each group. Vascular dementia model was established by repeatedly clipping bilateral carotid arteries. Each group was given corresponding dose (0.25 g / kg ~ 0.5 g 路kg ~ (-1) lg/kg) of dipsacus extract aqueous solution, sham operation, model group, equal volume distilled water, once a day, continuous oral administration for 21 days. The Miorris water maze is used to carry out the navigation experiment and the space exploration ability experiment. The levels of SOD,MDA and GSH in serum were determined by enzyme linked immunosorbent assay (Elisa). [result] 1. Acute toxicity tests cannot determine acute toxicity. At the maximal tolerance dose, the rats were observed continuously for 7 days, the movement, breathing, eating, drinking water, body hair, oral and nasal secretions, state and body weight were not abnormal, the animals were in good general state, no abnormal state and death. After dissection, no obvious abnormal changes were observed in the main organs. The maximum dose of dipsacus extract was 0.3g/ml 脳 40ml/kg 脳 3 times = 36g / kg, which was 135.2 times as much as that of adult dipsacus extract (16g/60kg). Effects of Dipsacus extract on the ability of Learning and memory in Vascular dementia Rats (2) the effect of Dipsacus extract on spatial memory and spatial exploration ability of rats: there was no significant difference between the two groups in the latency of searching for platform at the beginning of the first two days. From the third day onwards, the latency time of platform searching in the high dose group was significantly shorter than that in the model group (P0.05), and the number of platform crossing after the withdrawal of the platform was significantly higher than that in the model group (P0.05). 3 SOD,MDA, in serum of the rats in the high dose group was significantly shorter than that in the model group (P0.05). The effect of GSH: in the extract of Dipsacus, the content of SOD,GSH and the activity of MDA in the serum of high dose group were higher than those in the model group (P0.05). [conclusion] 1. For SD rats, the maximum dose of dipsacus extract was 36g / kg, which was 135 times that of adult's daily maximum dose, and had no obvious toxicity, indicating that the drug toxicity of Dipsacus extract was very low; 2. Dipsacus extract can improve the learning and memory ability of vascular dementia rats. It may be because it can increase the content of SOD,GSH and decrease the content of MDA in serum of rats.
【學(xué)位授予單位】：延邊大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R749.13

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