本文選題：梓葛凍干粉針 + 缺血性中風(fēng)　； 參考：《西南大學(xué)》2016年博士論文

【摘要】：1.研究背景抑制或減輕中風(fēng)急性期半暗帶細(xì)胞凋亡或死亡,避免梗死灶擴(kuò)大,是公認(rèn)的較為理想的缺血性中風(fēng)腦保護(hù)策略。課題組自主研制的抗中風(fēng)藥物——梓葛凍干粉針(由地黃藥效成分梓醇和葛根藥效成分葛根素組成),在永久缺血性腦中風(fēng)模型大鼠和小鼠的非急性期,以及缺血再灌注損傷的腦中風(fēng)模型大鼠中,均表現(xiàn)出較好的腦保護(hù)作用。然而,梓葛凍干粉針對永久缺血性腦中風(fēng)模型大鼠急性期的腦保護(hù)作用尚未觀察,其對腦缺血半暗帶中神經(jīng)血管單元細(xì)胞的整體保護(hù)作用及其可能的通路機(jī)制有待研究。本研究獲得了國家自然科學(xué)基金面上項(xiàng)目(81473549)、教育部博士學(xué)科點(diǎn)專項(xiàng)基金項(xiàng)目(博導(dǎo)類:20110182110012)、教育部中央高�；究蒲袠I(yè)務(wù)費(fèi)項(xiàng)目(XDJK2014D023)以及重慶市衛(wèi)生局中醫(yī)藥科研重大項(xiàng)目(渝中醫(yī)2010[60]2010-1-4)的支持。2.研究目的研究梓葛凍干粉針對永久缺血性腦中風(fēng)模型大鼠急性期的腦保護(hù)作用,以及對腦缺血半暗帶中神經(jīng)血管單元的整體保護(hù)作用和機(jī)制,為將梓葛凍干粉針開發(fā)成治療缺血性腦中風(fēng)的候選藥物提供基礎(chǔ)研究數(shù)據(jù)。3.方法與結(jié)果3.1梓葛凍干粉針對大鼠急性腦缺血損傷整體保護(hù)作用研究方法用線栓法梗塞大腦中動脈,復(fù)制大鼠中風(fēng)模型。在造模大鼠蘇醒2 h后,采用改良神經(jīng)功能缺損評分法(m NSS)進(jìn)行評分并分組。以m NSS評分得4分及以上且各項(xiàng)均有缺損為標(biāo)準(zhǔn),判定造模成功。將造模成功的64只大鼠隨機(jī)分為4個(gè)組,每組16只:模型組,梓葛凍干粉針65.4 mg·kg-1、32.7 mg·kg-1和16.4 mg·kg-1組。另設(shè)假手術(shù)組16只。尾靜脈注射梓葛凍干粉針或生理鹽水,一天2次,給藥1天。造模24 h后:(1)用m NSS評分法再次評價(jià)大鼠的神經(jīng)功能,并分析組間差異顯著性。(2)每組取8只大鼠麻醉處死,分離新鮮大腦用腦模切片,作TTC染色,拍照后,用軟件測算腦梗死面積百分比,并分析比較組間差異顯著性。(3)每組另取8只大鼠麻醉,灌流固定后分離大腦,冰凍切片后作HE染色,用顯微鏡觀察并拍照,比較組間腦缺血半暗帶組織的損傷情況。結(jié)果與假手術(shù)組相比,模型組大鼠m NSS得分和腦梗死面積百分比均顯著增加(p0.01),缺血區(qū)腦組織大面積壞死,部分區(qū)皮質(zhì)域呈高度疏松篩網(wǎng)狀結(jié)構(gòu),細(xì)胞結(jié)構(gòu)不清,紅色壞死神經(jīng)元顯著增加。與模型組相比,梓葛凍干粉針65.4mg·kg-1、32.7 mg·kg-1和16.4 mg·kg-1組大鼠m NSS得分和腦梗死面積百分比均顯著下降(p0.01、p0.05),缺血區(qū)腦組織壞死程度顯著減輕,紅色壞死神經(jīng)元顯著減少。3.2梓葛凍干粉針抗大鼠急性腦缺血損傷半暗帶保護(hù)機(jī)制研究方法造模及分組給藥方法同第一章,每組12只大鼠。造模24 h后:(1)每組取6只大鼠,按第一章方法制作大腦冰凍切片,用TUNEL+特異性蛋白雙重免疫熒光染色標(biāo)記腦片,熒光顯微鏡觀察缺血半暗帶大腦皮質(zhì)區(qū)神經(jīng)元、星形膠質(zhì)細(xì)胞和微血管內(nèi)皮細(xì)胞生長形態(tài)并拍照,用軟件分析3種細(xì)胞的凋亡率,并比較組間差異顯著性。(2)另取腦片,用免疫組化技術(shù)分別標(biāo)記Bax、Bcl-2、Caspase-3、Cleaved caspase-3和Cyt-C蛋白,用顯微鏡觀察缺血半暗帶大腦皮質(zhì)區(qū)并拍照。(3)每組另取6只大鼠麻醉取腦,提取缺血半暗帶大腦皮質(zhì)組織勻漿蛋白,用WB檢測勻漿蛋白中Bax、Bcl-2、Caspase-3、Cleaved caspase-3和Cyt-C蛋白表達(dá),并分析比較組間差異顯著性。結(jié)果與假手術(shù)組相比,模型組大鼠缺血半暗帶大腦皮質(zhì)層區(qū)域神經(jīng)元、星形膠質(zhì)細(xì)胞和微血管內(nèi)皮細(xì)胞的凋亡率顯著增加(p0.01),細(xì)胞生長形態(tài)嚴(yán)重受損,促細(xì)胞凋亡的Bax、Caspase-3、Cleaved caspase-3和Cyt-C蛋白表達(dá)均顯著增加(p0.01),抑制細(xì)胞凋亡的Bcl-2蛋白表達(dá)顯著減少(p0.01)。與模型組相比,梓葛凍干粉針65.4 mg·kg-1、32.7 mg·kg-1和16.4 mg·kg-1組大鼠缺血半暗帶大腦皮質(zhì)區(qū)域該3種細(xì)胞的凋亡率均顯著降低(p0.01),其生長形態(tài)明顯改善,上述促調(diào)蛋白表達(dá)均顯著減少(p0.01,p0.05);其中,梓葛凍干粉針65.4 mg·kg-1組大鼠Bcl-2蛋白表達(dá)顯著增加(p0.01)。3.3體外腦神經(jīng)血管單元半暗帶損傷模型的建立及梓葛凍干粉針的整體保護(hù)作用研究方法(1)大鼠大腦皮層神經(jīng)元、星形膠質(zhì)細(xì)胞和微血管內(nèi)皮細(xì)胞的原代培養(yǎng),以及由該3種細(xì)胞共培養(yǎng)組成的腦神經(jīng)血管單元模型的構(gòu)建,均參照課題組前期方法。(2)用文獻(xiàn)報(bào)道的半暗帶條件培養(yǎng)液,對所建立的腦神經(jīng)血管單元模型進(jìn)行損傷,24 h后,以細(xì)胞生長狀態(tài)、數(shù)量、軸突長度和細(xì)胞跨內(nèi)皮電阻值顯著(p0.05)低于正常培養(yǎng)孔為標(biāo)準(zhǔn),判定體外腦神經(jīng)血管單元半暗帶損傷模型構(gòu)建成功。(3)將構(gòu)建的腦神經(jīng)血管單元模型隨機(jī)分為5個(gè)組,每組6個(gè)孔:正常培養(yǎng)組、損傷模型組(半暗帶條件培養(yǎng)液損傷24 h)、梓葛凍干粉針3個(gè)劑量組(于更換半暗帶條件培養(yǎng)液時(shí)加入49.0μg·m L-1、24.5μg·m L-1以及12.25μg·m L-1的梓葛凍干粉針)。用藥24 h后,用顯微鏡觀察3種細(xì)胞的生長形態(tài)并拍照,用臺盼藍(lán)計(jì)數(shù)法檢測星形膠質(zhì)細(xì)胞和微血管內(nèi)皮細(xì)胞的活細(xì)胞數(shù)量,用圖像分析軟件測量神經(jīng)元軸突長度,用細(xì)胞電阻儀檢測模型中跨內(nèi)皮電阻值,并分析比較組間差異顯著性。結(jié)果(1)成功分離培養(yǎng)出高純度的大鼠大腦皮層3種原代細(xì)胞,構(gòu)建了由該3種細(xì)胞共培養(yǎng)的腦神經(jīng)血管單元整體模型。與單細(xì)胞培養(yǎng)相比,共培養(yǎng)模型中神經(jīng)元胞體圓潤且立體感強(qiáng),軸突更粗大且長并形成致密網(wǎng)絡(luò);腦微血管內(nèi)皮細(xì)胞和星形膠質(zhì)細(xì)胞胞間接觸更緊密,形成致密的單層;腦微血管內(nèi)皮細(xì)胞和星形膠質(zhì)細(xì)胞活細(xì)胞數(shù)量、神經(jīng)元軸突長度以及模型跨內(nèi)皮電阻值均顯著增加(p0.05,p0.01)。(2)與正常培養(yǎng)組相比,經(jīng)半暗帶條件培養(yǎng)液損傷的腦神經(jīng)血管單元整體模型組中,神經(jīng)元立體感較差,胞體和軸突變小,軸突網(wǎng)絡(luò)密度降低;腦微血管內(nèi)皮細(xì)胞和星形膠質(zhì)細(xì)胞胞體收縮,部分細(xì)胞出現(xiàn)脫落;腦微血管內(nèi)皮細(xì)胞和星形膠質(zhì)細(xì)胞活細(xì)胞數(shù)量、神經(jīng)元軸突長度以及跨內(nèi)皮電阻值均顯著降低(p0.01)。與半暗帶條件培養(yǎng)液損傷的腦神經(jīng)血管單元整體模型組相比,梓葛凍干粉針49.0μg·m L-1、24.5μg·m L-1以及12.25μg·m L-1組腦神經(jīng)血管單元整體模型中,神經(jīng)元胞體無明顯收縮,突觸網(wǎng)絡(luò)仍較緊密;微血管內(nèi)皮細(xì)胞和星形膠質(zhì)細(xì)胞胞體輕微收縮,胞間接觸仍較緊密;腦微血管內(nèi)皮細(xì)胞和星形膠質(zhì)細(xì)胞活細(xì)胞數(shù)量、腦神經(jīng)血管單元整體跨內(nèi)皮電阻值均顯著增加(p0.01);其中,梓葛凍干粉針49.0μg·m L-1和24.5μg·m L-1組神經(jīng)元軸突長度顯著增加(p0.01)。3.4梓葛凍干粉針抗體外腦神經(jīng)血管單元模型半暗帶損傷的機(jī)制研究方法(1)大鼠大腦皮層3種原代細(xì)胞的培養(yǎng)、腦神經(jīng)血管單元模型的構(gòu)建及體外腦神經(jīng)血管單元模型半暗帶損傷方法同第3章。(2)將構(gòu)建的腦神經(jīng)血管單元模型隨機(jī)分為7個(gè)組,每組6孔:正常培養(yǎng)組:在正常培養(yǎng)條件下培養(yǎng);損傷模型組:半暗帶條件培養(yǎng)液損傷24 h;梓葛凍干粉針3個(gè)劑量組:在更換半暗帶條件培養(yǎng)液時(shí)添加梓葛凍干粉針,使其終濃度分別為49.0μg·m L-1、24.5μg·m L-1、12.25μg·mm L-1;抑制劑MG132組:在更換半暗帶條件培養(yǎng)液時(shí)添加MG132,使其終濃度為10μM;49.0μg·mm L-1梓葛凍干粉針+MG132組:在更換半暗帶條件培養(yǎng)液時(shí),添加梓葛凍干粉針(49.0μg·m L-1)和MG132(10μM)。(3)用藥后,用流式細(xì)胞儀檢測不同組別腦神經(jīng)血管單元細(xì)胞共培養(yǎng)模型中3種細(xì)胞凋亡率,并分析比較組間差異顯著性。(4)用試劑盒提取不同組別腦神經(jīng)血管單元模型細(xì)胞總蛋白,蛋白定量后,按WB操作步驟,檢測分析Bax、Bcl-2、Caspase3、Cleaved caspase-3、Caspase-9、Cleaved caspase-9、Cyt-C、XIAP的蛋白表達(dá),并分析比較組間差異顯著性。結(jié)果與正常培養(yǎng)組相比,經(jīng)半暗帶條件培養(yǎng)液損傷的腦神經(jīng)血管單元模型組中,神經(jīng)元、星形膠質(zhì)細(xì)胞和微血管內(nèi)皮細(xì)胞凋亡率均顯著增加(p0.01),細(xì)胞Bax、Cyt-C、Cleaved caspase-9、Caspase-3和Cleaved caspase-3蛋白表達(dá)均顯著增加(p0.01),Bcl-2和XIAP蛋白表達(dá)顯著降低(p0.01)。與半暗帶條件培養(yǎng)液損傷的腦神經(jīng)血管單元整體模型組相比,梓葛凍干粉針49.0μg.m L-1及24.50μg.m L-1組該3種細(xì)胞的凋亡率均顯著降低(p0.01),Cyt-C、Cleaved caspase-9和Cleaved caspase-3的蛋白表達(dá)均顯著降低(p0.01),Bcl-2和XIAP的蛋白表達(dá)均顯著升高(p0.01),其中梓葛凍干粉針49.0μg·m L-1組Bax蛋白表達(dá)顯著降低(p0.01)。與梓葛凍干粉針49.0μg·m L-1組相比,MG132+梓葛凍干粉針49.0μg·m L-1組XIAP蛋白與Cleaved caspase-3蛋白表達(dá)均顯著增加(p0.01,p0.05)。4.研究結(jié)論4.1梓葛凍干粉針能減輕大鼠腦缺血區(qū)域受損細(xì)胞形態(tài)變化,減少細(xì)胞死亡,減少缺血區(qū)腦組織梗死灶面積,改善大鼠神經(jīng)功能,對大鼠急性腦缺血損傷發(fā)揮整體保護(hù)作用。4.2梓葛凍干粉針對大鼠急性腦缺血損傷的整體保護(hù)作用,主要是通過抑制缺血半暗帶區(qū)神經(jīng)元、星形膠質(zhì)細(xì)胞和微血管內(nèi)皮細(xì)胞凋亡實(shí)現(xiàn)的,其機(jī)制與調(diào)節(jié)線粒體凋亡通路有關(guān)。4.3梓葛凍干粉針對急性腦缺血半暗帶神經(jīng)血管單元細(xì)胞線粒體凋亡通路的調(diào)節(jié)作用,與促進(jìn)XIAP蛋白表達(dá)有關(guān)。4.4本研究中,體外腦神經(jīng)血管單元半暗帶模型損傷變化及梓葛凍干粉針的逆轉(zhuǎn)作用,與在體實(shí)驗(yàn)結(jié)果具有較高一致性。提示該模型可用于缺血半暗帶腦神經(jīng)血管單元細(xì)胞損傷機(jī)制研究及其保護(hù)藥物效果的體外評價(jià)。
[Abstract]:1. the research background suppresses or reduces the apoptosis or death of the cells in the acute phase of the apoplexy, and avoids the enlargement of the infarct. It is an ideal cerebral protection strategy for ischemic stroke. The cerebral apoplexy model rats and mice, as well as the cerebral apoplexy model rats with ischemia-reperfusion injury, showed better cerebral protective effect. However, the protective effect of Catalpol dry powder on the acute ischemic cerebral apoplexy rat model was not yet observed, and its neurovascular cell cells in the cerebral ischemic penumbra The overall protection and its possible pathway mechanisms need to be studied. This study obtained the National Natural Science Foundation Project (81473549), the special fund project of the doctoral program of the Ministry of Education (20110182110012), the basic scientific research service fee project (XDJK2014D023) of the central colleges and universities of the Ministry of Education and the importance of Chinese medicine in the Chongqing Municipal Health Bureau. The project (Chongqing Chinese medicine 2010[60]2010-1-4) supports.2. research to study the protective effect of Catalpol dry powder on the acute stage of acute ischemic cerebral apoplexy in rats, as well as the overall protective effect and mechanism of the neurovascular units in the cerebral ischemic penumbra, in order to develop a candidate drug for the treatment of ischemic stroke. The basic research data.3. method and results 3.1 The Study on the overall protective effect of Catalpol freeze-dried powder on acute cerebral ischemia injury in rats, the middle cerebral artery was infarcted by the thread emboli method, and the rat model of stroke was replicated. After the rats were awakened to 2 h, the improved neural function defect scoring (m NSS) was used to score and group. The score of M NSS score was 4 points. 64 rats were randomly divided into 4 groups, 16 rats in each group, with 16 rats in each group: model group, Catalpol freeze dry powder 65.4 mg. Kg-1,32.7 mg. Kg-1 and 16.4 mg. Kg-1. There were 16 in the sham operation group. The tail vein was injected Catalpol dry powder needle or saline, 2 times a day and 1 days. The model 24 was 24. After H: (1) the m NSS scoring method was used to reevaluate the nerve function of the rats and to analyze the difference between the groups. (2) 8 rats in each group were killed, and the fresh brain was separated by the brain model section to make TTC staining. The percentage of cerebral infarction was measured by software and the difference was statistically significant. (3) another 8 rats in each group were anaesthetized and perfusion. After the fixation, the brain was separated and the frozen section was stained with HE. The damage of the ischemic penumbra in the group was compared with the microscope. Results compared with the sham group, the scores of M NSS and the percentage of cerebral infarction increased significantly (P0.01), the cerebral tissue in the ischemic area was large and the cortical area was highly sparse. In the group of 65.4mg. Kg-1,32.7 mg. Kg-1 and 16.4 mg. Kg-1, the scores of M NSS and the percentage of infarcted area decreased significantly (P0.01, P0.05), and the necrosis degree of cerebral tissue in the ischemic area was significantly reduced and the red necrotic neurons were significant compared with the model group. To reduce the protection mechanism of.3.2 Catalpol freeze-dried powder for the protection of semi dark zone of acute cerebral ischemia injury in rats, the method of modeling and group administration is the same as the first chapter, 12 rats in each group. After 24 h, the model of cerebral frozen section is made in each group, and the brain slices are marked with TUNEL+ specific protein double immunofluorescence staining. Microscopically, the neurons, astrocytes and microvascular endothelial cells in the cerebral cortex of the ischemic penumbra were observed and photographed. The apoptosis rate of the 3 kinds of cells was analyzed with software. (2) the brain slices were taken and the Bax, Bcl-2, Caspase-3, Cleaved caspase-3 and Cyt-C protein were marked with immunohistochemical technique. The cerebral cortex area of ischemic half dark zone was observed and photographed. (3) another 6 rats in each group were taken to take the brain, and the cerebral cortex homogenate protein was extracted from the ischemic penumbra. The expression of Bax, Bcl-2, Caspase-3, Cleaved caspase-3 and Cyt-C protein in the homogenate protein was detected by WB, and the difference between the groups was statistically significant. The results were compared with the sham group, the model group was larger than the sham group. The apoptosis rate of astrocytes and microvascular endothelial cells increased significantly (P0.01), and the cell growth morphology was severely damaged. The expression of Bax, Caspase-3, Cleaved caspase-3 and Cyt-C protein increased significantly (P0.01), and the expression of Bcl-2 protein inhibited apoptosis significantly decreased (P0 (P0). .01). Compared with the model group, the apoptosis rate of the 3 cells in the ischemic half dark zone of the rats of 65.4 mg. Kg-1,32.7 mg. Kg-1 and 16.4 mg kg-1 group were significantly decreased (P0.01), and the expression of the TGP was significantly reduced (P0.01, P0.05). Among them, the Catalpol dry powder needle was 65.4 mg. The expression of Bcl-2 protein in rats increased significantly (P0.01) the damage model of the subdark zone of the neurovascular unit of the.3.3 body and the study method of the overall protection of the dry powder of Catalpol (1) the primary culture of the cerebral cortex neurons, astrocytes and microvascular endothelial cells in the rats, and the cerebral nerve blood composed of the 3 kinds of cells co culture. The construction of the tube unit model referred to the preliminary method of the project group. (2) using the semi dark zone conditioned medium reported in the literature, the brain nerve cell model was damaged. After 24 h, the cell growth state, the number, the axon length and the cell cross endothelial resistance value were significantly lower than the normal culture pore, and the brain nerve was determined in vitro. The model of vascular unit semi dark zone damage model was successfully constructed. (3) the constructed brain nerve cell model was randomly divided into 5 groups, with 6 holes in each group: normal culture group, injury model group (24 h damage of semi dark zone conditioned medium), and 3 dose groups of Catalpol freeze-dried powder (49 mu m L-1,24.5 G. M L-1 when replacing the semi dark zone conditioned medium. After 24 h, the growth morphology of 3 cells was observed with microscope and the number of living cells of astrocytes and microvascular endothelial cells were detected by trypan blue counting, and the length of the axon was measured by the image analysis software, and the resistance value of the endothelium in the model was detected by the cell resistance instrument, and the resistance value of the endothelium in the model was detected by the cell resistance instrument, and the resistance value of the 12.25 h L-1 was detected, and the resistance value of the model was detected by the cell resistance instrument. Results (1) 3 primary cells of the cerebral cortex of high purity rat were successfully isolated and cultured. The whole model of cerebral nerve cell unit was constructed by the 3 cells. Compared with the single cell culture, the cell body was round and strong in the co culture model, and the axon was thicker and more dense and dense. The intercellular contact between the cerebral microvascular endothelial cells and astrocytes was closer, forming a compact monolayer; the number of living cells in the brain microvascular endothelial cells and astrocytes, the length of the axon and the resistance value of the model were significantly increased (P0.05, P0.01). (2) compared with the normal culture group, the semi dark zone conditioned medium injury was damaged. In the whole model group of cerebral neurovascular unit, the stereoscopic sense of neuron was poor, the cell body and axon became smaller, the density of the axon network decreased, the cerebral microvascular endothelial cells and astrocytes were contracted, the part of the cell appeared to fall off, the number of the brain microvascular endothelial cells and astrocytes, the length of the neuron axon and the cross endothelial electricity. Compared with the whole model group of brain neurovascular unit damaged by semi dark zone conditioned medium, 49 mu g m L-1,24.5 G. M L-1 and 12.25 mu g. M L-1 group were compared with the whole model group. The neuronal cell body was not obviously contracted and the synapse network was still tight; microvascular endothelial cells and stars were still relatively close. The cell bodies of glial cells were slightly contracted and the intercellular contact was still close, the number of living cells in the cerebral microvascular endothelial cells and astrocytes, the overall cross endothelial resistance value of the brain neurovascular unit increased significantly (P0.01), and the length of the axon of the neurons of 49 mu g / m L-1 and the 24.5 mu g. L-1 group increased significantly (P0.01).3.4 Catalpol The mechanism of the semi dark zone damage of the freeze-dried powder needle antibody external brain neurovascular unit model (1) the cultivation of 3 primary cells in the cerebral cortex of the rats, the construction of the brain nerve cell model and the method of the damage of the semi dark band in the brain nerve cell model in the same third chapters. (2) the neural vascular unit model was randomly divided into 7 groups. Each group of 6 holes: normal culture group: cultured under normal culture conditions; damage model group: semi dark zone conditioned medium injury 24 h; zigge freeze-dried powder 3 doses group: adding Catalpol freeze-dried powder when replacing semi dark zone conditioned medium, the final concentration was 49 mu. M L-1,24.5, m L-1,12.25 mu g. Mm L-1; inhibitor MG132 group: in addition, inhibitor MG132 group: in more Adding MG132 to the medium dark zone conditioned medium, the final concentration was 10 mu M; 49 G. Mm L-1 catalpa freeze-dried powder needle +MG132 group: adding Catalpol freeze-dried powder needle (49 mu g. M L-1) and MG132 (10 mu M) when replacing the semi dark zone conditioned medium. (3) using flow cytometry to detect the co culture model of cerebral nerve cell cell cell in different groups 3 (4) the total protein of the brain nerve cell model of different groups was extracted with the kit. After the WB operation, the protein expression of Bax, Bcl-2, Caspase3, Cleaved Caspase-3, Caspase-9, Cleaved caspase-9, Cyt-C, XIAP were detected and analyzed, and the differences between the groups were analyzed and compared. The apoptosis rate of neurons, astrocytes and microvascular endothelial cells increased significantly (P0.01), and the expression of Bax, Cyt-C, Cleaved caspase-9, Caspase-3 and Cleaved caspase-3 proteins increased significantly (P0.01), Bcl-2 and X, compared with the normal culture group. The expression of IAP protein was significantly decreased (P0.01). Compared with the whole model group, the apoptosis rates of the 3 kinds of cells were significantly decreased (P0.01), and the protein expressions of Cyt-C, Cleaved caspase-9 and Cleaved caspase-3 were significantly decreased. The expression of protein in XIAP and XIAP increased significantly (P0.01), and the expression of Bax protein in the 49 u g / m L-1 group was significantly decreased (P0.01). Compared with the 49 mu g / m L-1 group of Catalpol freeze-dried powder, the expression of 49 mu g. GL dry powder can reduce the morphological changes of damaged cells in the cerebral ischemia area of rats, reduce cell death, reduce the area of cerebral infarction in the ischemic area, improve the nerve function of rats, and play an integral protective effect on the acute cerebral ischemia injury in rats. The main protective effect of.4.2 Catalpol dry powder on acute cerebral ischemia injury in rats is mainly through the protection. Inhibiting the apoptosis of neurons, astrocytes and microvascular endothelial cells in the ischemic penumbra region, its mechanism is related to regulation of mitochondrial apoptosis pathway related to the regulation of.4.3 Catalpol dry powder on the mitochondrial apoptosis pathway in the acute cerebral ischemic penumbra cell cell cells, which is related to the.4.4 study of promoting the expression of XIAP protein. The changes in the damage of the semi dark zone model of the neurovascular unit of the outer brain and the reversal effect of Catalpol freeze-dried powder needle are in good agreement with the experimental results, suggesting that the model can be used to study the mechanism of cell damage in the ischemic penumbra and the evaluation of the drug effect in vitro.
【學(xué)位授予單位】：西南大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2016
【分類號】：R285.5

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