本文選題：抑郁 + 谷氨酸代謝�。� 參考：《廣州中醫(yī)藥大學(xué)》2016年博士論文

【摘要】：目的：通過觀察電針及手針四關(guān)穴對慢性不可預(yù)見性溫和刺激致郁大鼠行為學(xué)及腦內(nèi)谷氨酸代謝功能的影響,對比兩種針刺方法改善CUMS大鼠抑郁行為的效應(yīng)差異,并探討其內(nèi)在機制。實驗一 電針與手針四關(guān)穴改善CUMS大鼠行為的效應(yīng)比較方法：1.動物分組雄性SD大鼠60只,體重220-270g,隨機分為5組：空白組、模型組、電針組、手針組、藥物組,每組12只。2.干預(yù)措施空白組3只/籠,正常飼養(yǎng)。模型組、電針組、手針組與藥物組采用慢性不可預(yù)見性溫和刺激聯(lián)合孤養(yǎng)方法建立抑郁大鼠模型(選擇7種不同溫和刺激,每日施加一種刺激,連續(xù)施加35日)。行為學(xué)結(jié)果提示造模成功后開始治療,治療期間各組大鼠進行相同程度的捉抓與束縛。(1)模型組：建模成功后不予其他干預(yù)。(2)電針組：建模成功后第二日予電針四關(guān)穴,連續(xù)波,頻率2Hz,留針30min,強度以見大鼠肢體微微顫抖而未嘶叫為度；治療第一周每日一次,治療第二、第三周每兩日一次。(3)手針組：建模成功后第二日予針刺四關(guān)穴,施捻轉(zhuǎn)行針法,平補平瀉,每10min行針1次,每次捻轉(zhuǎn)10s,留針30min；療程同電針組。(4)藥物組：造模成功第二日予利魯唑灌胃治療(4mg/kg, i.p),每12h灌胃一次,連續(xù)治療3周。3.行為學(xué)評價指標在造模前、造模3周結(jié)束時及造模5周結(jié)束時對各組大鼠進行體質(zhì)量、糖水偏好率、曠場實驗及Morris水迷宮實驗檢測,以評價造模成功與否：在治療1周結(jié)束時及治療3周結(jié)束時對各組大鼠進行上述行為學(xué)檢測,評價電針、手針與西藥的治療效應(yīng)。4.統(tǒng)計分析采用SPSS20.0統(tǒng)計軟件整理數(shù)據(jù),計量資料采用均數(shù)±標準差表示；各行為學(xué)檢測評分組間比較在重復(fù)測量方差分析基礎(chǔ)上,進行正態(tài)性檢驗及方差齊性檢驗,符合正態(tài)分布及方差齊性檢驗則選用單因素方差分析,檢驗標準P0.05。若不符合者則選用Kruskal-Wallis H秩和檢驗觀察整體差異,進一步采用wilcoxon秩和檢驗兩兩比較,采用SPSS調(diào)整后顯著性結(jié)果,檢驗標準P0.05。實驗室計量資料則根據(jù)正態(tài)性檢驗及方差齊性檢驗結(jié)果選用單因素方差分析或秩和檢驗。結(jié)果：1.電針、手針與利魯唑?qū)UMS大鼠體質(zhì)量的影響CUMS造模5周后,與空白組比較,各造模組體重顯著下降(P0.05)；治療3周后,與模型組比較,電針組、手針組與西藥組體重顯著增加(P=0.022,P=0.004,P0.001)；西藥組與手針組療效相當(dāng),電針組與西藥組差異有統(tǒng)計學(xué)意義(P=0.019)。2.電針、手針與利魯唑?qū)UMS大鼠糖水偏好的影響CUMS造模5周后,與空白組比較,各造模組糖水偏好率顯著降低(P0.05)；治療3周后,與模型組比較,電針組、手針組與西藥組糖水偏好率顯著升高(均為P0.001)；各組療效比較無統(tǒng)計學(xué)差異(P0.05)。3.電針、手針與利魯唑?qū)UMS大鼠曠場實驗評分的影響①水平活動：CUMS造模5周后,與空白組比較,各造模組水平活動顯著減少(P0.001)；治療3周后,與模型組比較,電針組、手針組與西藥組水平活動均有增加,手針與西藥組有統(tǒng)計學(xué)差異(P=0.234,P=0.038,P=0.038)；手針組與西藥組療效相當(dāng)(P0.05)。②垂直活動：CUMS造模5周后,與空白組比較,各造模組垂直活動顯著減少(P0.05)；治療3周后,與模型組比較,電針組、手針組與西藥組垂直活動均有增加,手針組有統(tǒng)計學(xué)差異(P=0.58,P=0.035,P=0.177)。4.電針、手針與利魯唑?qū)UMS大鼠Morris水迷宮評分的影響①潛伏期：CUMS造模5周后,與空白組比較,各造模組潛伏期明顯高于空白組(P0.05)；治療3周后,與模型組比較,電針組、手針組與西藥組潛伏期均有縮短,手針組、西藥組有統(tǒng)計學(xué)差異(P=0.168,P=0.016,P=0.007)；手針組與西藥組療效比較無統(tǒng)計學(xué)差異(P0.05)。②總距離：CUMS造模5周后,與空白組比較,各造模組移動總距離明顯大于空白組(P0.001)；治療3周后,與模型組比較,電針組、手針組與西藥組移動總距離均有縮短,電針組有統(tǒng)計學(xué)差異(P=0.015,P=0.079,P=0.123)。實驗二電針與手針四關(guān)穴改善CUMS大鼠腦內(nèi)As功能的效應(yīng)比較方法：1.動物分組與處理同實驗一2.評價指標采用Western blot技術(shù)與Q-PCR技術(shù)觀察治療結(jié)束時各組大鼠海馬與前額葉皮層星形膠質(zhì)細胞膠質(zhì)纖維酸性蛋白(GFAP)及其mRNA表達量的變化。3.數(shù)據(jù)處理與統(tǒng)計同實驗一結(jié)果：1.海馬腦區(qū)GFAP與GFAP mRNA表達量①GFAP含量：與空白組比較,模型組GFAP含量降低(P=0.002)；與模型組比較,電針組、手針組與西藥組GFAP含量明顯升高(P=0.003,P=0.007,P=0.003)；電針組、手針組與西藥組比較無統(tǒng)計學(xué)差異(P0.05)。②GFAP mRNA表達量：與空白組比較,模型組GFAP mRNA表達量降低(P0.001)；與模型組比較,電針組、手針組與西藥組GFAP mRNA表達量明顯升高(P=0.003,P=0.011,P=0.001)；電針組、手針組與西藥組比較無統(tǒng)計學(xué)差異(P0.05)。2.前額葉皮層腦區(qū)GFAP與mRNA表達量①GFAP含量：與空白組比較,模型組GFAP含量降低(P=0.001)；與模型組比較,電針組、手針組與西藥組GFAP含量明顯升高(P=0.019,P=0.004,P=0.001)；電針組、手針組與西藥組比較無統(tǒng)計學(xué)差異(P0.05)。②GFAP mRNA表達量：與空白組比較,模型組GFAP mRNA表達量降低(P=0.006)；與模型組比較,電針組、手針組與西藥組GFAP mRNA表達量均有升高,電針組、西藥組有統(tǒng)計學(xué)差異(P=0.016,P=0.061,P=0.017)；電針組與西藥組比較無統(tǒng)計學(xué)差異(P0.05)。實驗三電針與手針四關(guān)穴改善CUMS大鼠腦內(nèi)GS功能的效應(yīng)比較方法：1.動物分組與處理同實驗一2.評價指標采用W estern blot技術(shù)與Q-PCR技術(shù)觀察治療后各組大鼠海馬與前額葉皮層內(nèi)谷氨酰胺酶(GS)及其mRNA表達量的變化。3.數(shù)據(jù)處理與統(tǒng)計同實驗一結(jié)果：1.海馬腦區(qū)GS及其mRNA表達量①GS含量：與空白組比較,模型組GS含量降低(P0.001)；與模型組比較,電針組、手針組與西藥組GS含量明顯升高(均為P0.001)；電針組、手針組與西藥組比較無統(tǒng)計學(xué)差異(P0.05)。②GS mRNA表達量：與空白組比較,模型組GS mRNA表達量降低(P=0.018)；與模型組比較,電針組、手針組與西藥組GS mRNA表達量均有升高,電針組與西藥組有統(tǒng)計學(xué)差異(P=0.019,P=0.036,P=0.007)；電針組、與西藥組比較無統(tǒng)計學(xué)差異(P0.05)。2.前額葉皮層腦區(qū)GS及其mRNA表達量①GS含量：與空白組比較,模型組GS含量降低(P=0.002);與模型組比較,電針組、手針組與西藥組GS含量明顯升高(P=0.032,P=0.015,P=0.001)；電針組、手針組與西藥組比較無統(tǒng)計學(xué)差異(P0.05)。②GS mRNA表達量：與空白組比較,模型組GS mRNA表達量降低(P=0.006)；與模型組比較,電針組、手針組與西藥組GS mRNA表達量均有升高,電針組與西藥組有統(tǒng)計學(xué)差異(P=0.018,P=0.015,P0.001)；電針組與西藥組比較無統(tǒng)計學(xué)差異(P0.05)。實驗四基于1H-[13C]-NMR比較變電針與手針四關(guān)穴對CumS大鼠腦內(nèi)谷氨酸代謝的影響方法：1.動物分組與處理同實驗一2.評價指標采用1H-[13C]-NMR技術(shù)觀察治療后各組大鼠海馬與前額葉皮層內(nèi)經(jīng)星形膠質(zhì)細胞代謝產(chǎn)生的谷氨酸(Glu-C4)、谷氨酰胺(Gln-C4)及γ-氨基丁酸(GABA-C2)含量的變化。3.數(shù)據(jù)處理與統(tǒng)計同實驗一結(jié)果(1)海馬谷氨酸-C4、谷氨酰胺-C4及Y-氨基丁酸-C2的富集量谷氨酸-C4：CUMS造模5周后,與空白組比較,模型組富集量顯著下降(P=0.034)；治療3周后,與模型組比較,電針組、手針組與西藥組富集量有上升趨勢,但無統(tǒng)計學(xué)差異(P0.05)。谷氨酰胺-C4：CUMS造模5周后,與空白組比較,模型組富集量顯著下降(P=0.034)；治療3周后,與模型組比較,電針組、手針組與西藥組富集量有上升趨勢,但無統(tǒng)計學(xué)差異(P0.05)。Y-氨基丁酸-C2-CUMS造模5周后,與空白組比較,模型組富集量顯著降低(P0.001);治療3周后,與模型組比較,電針組、手針組與西藥組富集量明顯上調(diào)(P=0.001,P0.001)；手針組優(yōu)于電針組,差異有統(tǒng)計學(xué)意義(P=0.015),與西藥組療效相當(dāng)(P0.05)。(2)前額葉皮層谷氨酸-C4、谷氨酰胺-C4及Y-氨基丁酸-C2的富集量谷氨酸-C4:CUMS造模5周后,與空白組比較,模型組富集量顯著下降(P0.001)；治療3周后,與模型組比較,電針組、手針組與西藥組富集量有顯著回升(P=0.002,P=0.001, P=0.002),電針組、手針組與西藥組比較無統(tǒng)計學(xué)差異(P0.05)。谷氨酰胺-C4-CUMS造模5周后,與空白組比較,模型組富集量顯著降低(P=0.001)；治療3周后,與模型組比較,電針組、手針組與西藥組富集量顯著升高(P=0.019,P=0.007, P=0.001)；電針組、手針組與西藥組比較無統(tǒng)計學(xué)差異P0.05)。Y-氨基丁酸-C2:CUMS造模5周后,與空白組比較,模型組富集量顯著降低(P=0.034);治療3周后,與模型組比較,電針組、手針組與西藥組差異無統(tǒng)計學(xué)意義(P0.05)。結(jié)論：電針與手針四關(guān)穴可改善CUMS大鼠體重降低、糖水偏好率下降、活動能力減退等抑郁樣行為,與利魯唑相當(dāng)；其中手針四關(guān)穴在改善自主活動及探索行為方面有優(yōu)于電針與利魯唑的趨勢。電針與手針四關(guān)穴可提高CUMS大鼠海馬及前額葉皮層的GFAP、GS、谷氨酸-C4、谷氨酰胺-C4及Y-氨基丁酸-C2的表達量；因此調(diào)控腦內(nèi)谷氨酸的分解與代謝可能是其發(fā)揮抗抑郁效應(yīng)的內(nèi)在機制；其中手針四關(guān)穴在提高星形膠質(zhì)細胞對谷氨酸代謝量方面有優(yōu)于電針趨勢,與利魯唑類同。
[Abstract]:Objective: To observe the effect of electroacupuncture and hand needle four point on the behavior of rats with chronic unforeseeable mild stimulation and the function of glutamic acid metabolism in the brain, and compare the difference of the effect of two kinds of acupuncture methods to improve the depressive behavior of CUMS rats, and explore the internal mechanism. The effect of the experimental acupuncture and the hand needle four point on the behavior of CUMS rats is improved. 1. male SD rats were divided into 5 groups randomly: blank group, model group, electroacupuncture group, hand needle group, drug group, 12.2. intervention group in each group 3 / cage, normal feeding, model group, electroacupuncture group, hand acupuncture group and drug group established by chronic unforeseeable mild stimulation combined soliton method. The rat model of depression was selected (7 different mild stimuli, one stimulus was exerted daily for 35 days). The behavioral results suggested that the model was successfully treated after the model was successful. (1) the model group: the model group did not interfere with his intervention. (2) the electroacupuncture group: Second days after the successful modeling, the electroacupuncture group was given. Four, continuous wave, continuous wave, frequency 2Hz, retention of needle 30min, strength to see the limbs of rats trembling and not hoarse; treatment for the first week, second, third weeks once every two days. (3) hand acupuncture group: the second days after the modeling successful acupuncture four point, twisting and transferring needle, flat supplement, 1 times each 10min needle, twist 10s, leave needle 30m each time In; course of treatment with electroacupuncture group. (4) drug group: 4mg/kg (i.p) was given to ralurazole (i.p) for second days, and every 12h was given to the stomach once, and the evaluation indexes of.3. behavior for 3 weeks were at the end of the model, at the end of the model and at the end of the model for 5 weeks, the body mass, the sugar water preference rate, the open field experiment and the Morris water maze test were tested. Test to evaluate the success of the model: at the end of 1 weeks of treatment and at the end of the 3 week of treatment, the behavioral tests were carried out at the end of the 1 weeks and at the end of the treatment. The statistical analysis of the therapeutic effect of electroacupuncture, hand needle and Western Medicine was made by the statistical analysis of SPSS20.0 software, and the measurement data were expressed by mean number of standard deviation, and the comparison between the scores of behavioral test scores was compared. On the basis of the repeated measurement of variance analysis, the normal test and variance homogeneity test were carried out. The single factor variance analysis was selected according to the normal distribution and variance homogeneity test. If the standard P0.05. was not conformed, the Kruskal-Wallis H rank sum test was selected to observe the whole difference, and the Wilcoxon rank sum test 22 was compared, and SPSS was adopted. After the adjustment, the standard P0.05. laboratory measurement data were selected by single factor variance analysis or rank sum test according to normal test and variance homogeneity test. Results 1. electroacupuncture, hand acupuncture and ralurazole effect on the body mass of CUMS rats. After 5 weeks, the body weight of each model group decreased significantly (P0.05) compared with the empty white group. After 3 weeks of treatment, compared with the model group, the weight of electroacupuncture group, hand acupuncture group and Western medicine group increased significantly (P=0.022, P=0.004, P0.001), the curative effect of the western medicine group and the hand needle group was equal, the difference between the electroacupuncture group and the western medicine group was statistically significant (P=0.019).2. electroacupuncture, the effect of hand acupuncture and ralurazole on the sugar water preference of CUMS rats CUMS after the establishment of CUMS model, compared with the blank group. The sugar water preference rate of each model group decreased significantly (P0.05). After 3 weeks of treatment, the sugar water preference rate of the electroacupuncture group, the hand needle group and the western medicine group increased significantly (P0.001) compared with the model group, and there was no statistical difference (P0.05).3. electroacupuncture, hand needle and ralurazole on the open field test score of CUMS rats: level activity: CUMS model 5 After 3 weeks, compared with the model group, the level activity of the acupuncture group and the western medicine group increased, the hand needle and the western medicine group had a statistical difference (P=0.234, P=0.038, P=0.038), and the hand acupuncture group and the western medicine group had the same effect (P0.05). (2) the vertical activity: the CUMS model was made for 5 weeks. After 3 weeks of treatment, the vertical activity of the electroacupuncture group, hand needle group and Western medicine group increased, and the hand acupuncture group had statistical difference (P=0.58, P=0.035, P=0.177).4. electroacupuncture, hand acupuncture and ralurazole on the CUMS rat Morris water maze score. The incubation period: CUMS After 5 weeks, the incubation period of each model group was significantly higher than that in the blank group (P0.05). After 3 weeks of treatment, the latency of electroacupuncture group, hand needle group and Western medicine group shortened, hand acupuncture group and Western medicine group had statistical difference (P=0.168, P=0.016, P= 0.007), and there was no statistical difference between the hand needle group and the western medicine group (P0.05). Total distance: after 5 weeks of CUMS modeling, the total distance of each model group was significantly greater than that of the blank group (P0.001). After 3 weeks of treatment, the total distance between the electroacupuncture group, the hand acupuncture group and the western medicine group shortened, and the electroacupuncture group had a statistical difference (P=0.015, P=0.079, P=0.123). The experiment two electroacupuncture and hand needle four point improved CUMS big. The comparison of the effects of As function in the rat brain: 1. group and treatment of animals with the same experiment one 2. evaluation index using Western blot technique and Q-PCR technology to observe the changes of astroglia glial fibrillary acidic protein (GFAP) and mRNA expression in the hippocampus and prefrontal cortex of rats at the end of the treatment and.3. data processing and statistics of the same experiment Results: 1. the content of GFAP and GFAP mRNA expression in the hippocampus of the hippocampus: the content of GFAP: compared with the blank group, the GFAP content of the model group decreased (P=0.002). Compared with the model group, the GFAP content in the electroacupuncture group, the hand acupuncture group and the western medicine group increased significantly (P=0.003, P=0.007, P=0.003), and there was no statistical difference between the hand acupuncture group and the western medicine group (P0.05). Compared with the blank group, the expression of GFAP mRNA in the model group decreased (P0.001). Compared with the model group, the expression of GFAP mRNA in the electroacupuncture group, hand needle group and Western medicine group increased significantly (P=0.003, P=0.011, P=0.001), and there was no significant difference between the hand acupuncture group and the western medicine group (P0.05) in the electroacupuncture group (P0.05).2. prefrontal cortex brain region GFAP and mRNA expression content (1) content Compared with the blank group, the content of GFAP in the model group decreased (P=0.001). Compared with the model group, the content of GFAP in the electroacupuncture group and the western medicine group increased significantly (P=0.019, P=0.004, P=0.001), and there was no statistical difference between the acupuncture group and the western medicine group (P0.05). (2) the mRNA expression of GFAP in the group was lower than that in the blank group, and the GFAP mRNA expression in the model group was reduced. P=0.006); compared with the model group, the expression of GFAP mRNA in electroacupuncture group, hand acupuncture group and Western medicine group increased, and there was statistical difference between the electroacupuncture group and the western medicine group (P=0.016, P=0.061, P=0.017); there was no statistical difference between the electroacupuncture group and the western medicine group (P0.05). Experimental three electroacupuncture and hand needle four points improved the effect of GS function in the brain of CUMS rats: 1. W estern blot and Q-PCR techniques were used to evaluate the changes of glutaminase (GS) and mRNA expression in the hippocampus and prefrontal cortex of rats by W estern blot technique and Q-PCR technique. The results were as follows: GS in the hippocampus and the mRNA expression of GS in the hippocampus: compared with the blank group The content of GS in the model group decreased (P0.001); compared with the model group, the GS content in the electroacupuncture group and the western medicine group increased significantly (all P0.001); the electroacupuncture group, the hand acupuncture group and the western medicine group had no statistical difference (P0.05). The GS mRNA expression was compared with the blank group, the GS mRNA expression in the model group decreased (P=0.018); compared with the model group, the electroacupuncture group was compared with the model group, and the electroacupuncture group, The expression of GS mRNA in the hand acupuncture group and the western medicine group increased, and there was a statistical difference between the electroacupuncture group and the western medicine group (P=0.019, P=0.036, P=0.007). There was no statistical difference between the electroacupuncture group and the western medicine group (P0.05) the GS of the prefrontal cortex and the mRNA expression of GS in the.2. prefrontal cortex (P0.05): the GS content of the model group was lower than that in the blank group (P=0.002); compared with the model group, it was compared with the model group. The content of GS in electroacupuncture group, hand acupuncture group and Western medicine group increased significantly (P=0.032, P=0.015, P=0.001), and there was no statistical difference between the acupuncture group and the western medicine group (P0.05). The expression of GS mRNA was compared with the blank group, and the GS mRNA expression in the model group decreased (P=0.006), and the expression of GS mRNA in the electroacupuncture group and the hand acupuncture group and the western medicine group were all compared with the model group. There was a statistical difference between the electroacupuncture group and the western medicine group (P=0.018, P=0.015, P0.001), and there was no statistical difference between the electroacupuncture group and the western medicine group (P0.05). Experiment four based on 1H-[13C]-NMR, the methods of comparing the effects of variable electroacupuncture and hand needle four point on the metabolism of glutamic acid in the brain of CumS rats: 1. animal groups and treatment with experimental one 2. evaluation index using 1H-[13 C]-NMR technique observed the changes of glutamic acid (Glu-C4), glutamine (Gln-C4) and gamma aminobutyric acid (GABA-C2) in the hippocampus and prefrontal cortex of rats after treatment with.3. data processing and statistical data processing and statistical results (1) hippocampus glutamic acid -C4, glutamine -C4 and Y- aminobutyric acid -C2 concentration of glutamic acid After 5 weeks of acid -C4:CUMS, the concentration of the model group decreased significantly compared with the blank group (P=0.034). After 3 weeks of treatment, the concentration of the electroacupuncture group, the hand needle group and the western medicine group increased, but there was no statistical difference (P0.05). After 5 weeks of the glutamine -C4:CUMS model, the concentration of the model group decreased significantly (P=0.034 After 3 weeks of treatment, compared with the model group, the concentration of the electroacupuncture group, the hand needle group and the western medicine group increased, but there was no statistical difference (P0.05).Y- aminobutyric acid -C2-CUMS for 5 weeks. Compared with the blank group, the concentration of the model group decreased significantly (P0.001). After 3 weeks of treatment, the concentration of the electroacupuncture group, the hand needle group and the western medicine group was obviously higher than the model group. P=0.001 (P0.001); hand acupuncture group was better than electroacupuncture group, the difference was statistically significant (P=0.015), compared with the western medicine group (P0.05). (2) after 5 weeks of glutamic acid -C4 in prefrontal cortex, glutamine -C4 and Y- aminobutyric acid -C2, the concentration of the model group decreased significantly (P0.001) compared with the empty white group (P0.001); after 3 weeks, and after treatment, Compared with the model group, the concentration of the electroacupuncture group and the western medicine group increased significantly (P=0.002, P=0.001, P=0.002). There was no statistical difference between the electroacupuncture group and the western medicine group (P0.05). After 5 weeks of the glutamine -C4-CUMS model, the concentration of the model group decreased significantly (P=0.001). After 3 weeks of treatment, the electroacupuncture group was compared with the model group, electroacupuncture group, The concentration of the hand acupuncture group and the western medicine group increased significantly (P=0.019, P=0.007, P=0.001), and in the electroacupuncture group, there was no statistical difference between the hand acupuncture group and the western medicine group (P0.05). After 5 weeks, the concentration of.Y- aminobutyric acid -C2:CUMS was significantly reduced (P=0.034) compared with the blank group. After 3 weeks of treatment, the difference between the electroacupuncture group, the hand acupuncture group and the western medicine group was compared with the model group. No statistical significance (P0.05). Conclusion: Electroacupuncture and hand needle four point can improve the weight loss of CUMS rats, decrease the sugar water preference rate and decrease the activity ability, which is equivalent to raluzole, and the four point of hand needle is superior to electroacupuncture and raluzole in improving autonomic activity and exploration behavior. Electroacupuncture and hand needle four point can be used. Improve the expression of GFAP, GS, glutamic acid -C4, glutamine -C4 and Y- aminobutyric acid -C2 in the hippocampus and prefrontal cortex of CUMS rats; therefore, the regulation of the decomposition and metabolism of glutamic acid in the brain may be an intrinsic mechanism for its antidepressant effect. The four point of hand needle is superior to electricity in improving the metabolism of glutamic acid in glutamic cells. The needle trend is the same as that of ralurazole.

【學(xué)位授予單位】：廣州中醫(yī)藥大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2016
【分類號】：R245

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