本文選題：創(chuàng)傷性顱腦損傷 + 膜粘連蛋白Ⅱ��； 參考：《重慶醫(yī)科大學(xué)》2015年博士論文

【摘要】：第一部分 膜粘連蛋白Ⅱ通過保護血腦屏障對小鼠顱腦創(chuàng)傷后早期神經(jīng)功能恢復(fù)的影響目的：評估外源性重組A2對創(chuàng)傷性顱腦損傷后早期神經(jīng)功能預(yù)后以及血腦屏障的影響,探討A2作為腦創(chuàng)傷治療靶點的可能性。方法：實驗一：內(nèi)源性A2蛋白在CCI后不同時間點和不同細(xì)胞內(nèi)表達的變化在成年雄性小鼠上建立精確皮質(zhì)打擊模型,檢測傷前與傷后不同時間點(6小時,1天,3天,5天,7天,14天,21天)傷側(cè)半球腦組織A2蛋白的表達；用CD31、GFAP、NeuN分別標(biāo)記內(nèi)皮細(xì)胞、星形膠質(zhì)細(xì)胞和神經(jīng)元,再與A2抗體行雙重染色檢測傷后A2在不同細(xì)胞類型中表達的變化情況。實驗二：外源性A2蛋白對CCI后BBB通透性、腦水腫以及海馬神經(jīng)元存活的影響體外培養(yǎng)內(nèi)皮細(xì)胞并建立損傷模型,檢測rA2對傷后內(nèi)皮細(xì)胞電阻、內(nèi)皮細(xì)胞屏障通透性和內(nèi)皮細(xì)胞活力的影響；小鼠CCI傷后通過靜脈注射伊文思藍染料并測定半球染料含量,檢測rA2對BBB通透性的影響；通過干濕重法測定傷后大腦半球組織含水量,檢測rA2對傷后腦水腫的影響；免疫組織熒光對CCI后海馬區(qū)神經(jīng)元進行標(biāo)記并定量,檢測rA2傷后海馬神經(jīng)元存活的影響；給予離體缺氧處理的神經(jīng)元中加入內(nèi)皮細(xì)胞條件培養(yǎng)基,檢測rA2通過內(nèi)皮細(xì)胞對受損神經(jīng)元的細(xì)胞活力影響。實驗三：外源性A2蛋白對CCI后早期神經(jīng)功能恢復(fù)和傷灶體積的影響通過NSS評分、Wire-gripping實驗分別對CCI傷后小鼠進行檢測,觀察rA2對顱腦創(chuàng)傷后早期神經(jīng)功能恢復(fù)的影響；對CCI傷后小鼠的組織切片進行HE染色,觀察rA2對顱腦創(chuàng)傷后傷灶體積的影響。實驗四：外源性A2蛋白對腦損傷后BBB保護作用的機制通過明膠酶譜法,檢測rA2對顱腦創(chuàng)傷后腦組織MMP-9活性的影響；通過對傷側(cè)腦組織中蛋白質(zhì)定量,檢測rA2對顱腦創(chuàng)傷后VEGF、 Occludin、Claudin-5和ZO-1表達的影響；建立體外內(nèi)皮細(xì)胞損傷模型,檢測rA2對內(nèi)皮細(xì)胞應(yīng)力纖維形成的影響。結(jié)果：實驗一：從傷后3天起,A2表達明顯增高(P0.05),并在7天時達到高峰(P0.05)。此后,蛋白表達逐漸下降,21天時恢復(fù)到基值。對比傷前與傷后免疫組織熒光結(jié)果,傷前內(nèi)皮細(xì)胞幾乎不表達A2,傷后在傷側(cè)部分內(nèi)皮細(xì)胞表達A2；傷前星形膠質(zhì)細(xì)胞部分表達A2,傷后雙側(cè)膠質(zhì)細(xì)胞均有活化,且活化的膠質(zhì)細(xì)胞都能表達A2；神經(jīng)元細(xì)胞在傷前已有A2表達,傷后未見明顯改變。實驗二：在內(nèi)皮細(xì)胞損傷后rA2能顯著提高內(nèi)皮細(xì)胞電阻(P0.05)和細(xì)胞活力(P0.05),并降低FITC-dextran通過內(nèi)皮細(xì)胞屏障的數(shù)量(P0.05)；通過在傷后不同時間點(2小時,4小時,6小時)將不同劑量rA2 (0.75mg/kg, 1mg/kg,1.5mg/kg)通過尾靜脈注入小鼠體內(nèi),均能顯著降低傷后腦組織EB滲出量(P0.05)；給予rA2不能顯著改變傷后腦組織水腫狀況(P0.05)；rA2能顯著減少傷后7天CA1和CA3區(qū)神經(jīng)元丟失,減輕海馬區(qū)結(jié)構(gòu)破壞(P0.05)；給予rA2的內(nèi)皮細(xì)胞條件培養(yǎng)基能顯著提高缺氧損傷神經(jīng)元的活力(P0.05)。實驗三：NSS評分結(jié)果證實rA2能顯著提高傷后7天內(nèi)運動相關(guān)行為學(xué)表現(xiàn)(P0.05),Wire-gripping實驗中rA2組小鼠的表現(xiàn)與對照組無顯著差別(P0.05)；HE染色證實給予rA2后傷灶體積無明顯改變(P0.05)。實驗四：rA2對傷后7天小鼠腦組織MMP-9活性無顯著影響(P0.05)；rA2對傷后7天小鼠腦組織中VEGF、Occludin和Claudin-5表達無顯著影響(P0.05)；rA2能顯著增加傷后7天小鼠腦組織中ZO-1表達(P0.05)；給予rA2后受損的內(nèi)皮細(xì)胞內(nèi)的應(yīng)力纖維數(shù)量顯著降低(P0.05)。結(jié)論：在創(chuàng)傷性顱腦損傷早期,rA2能提高內(nèi)皮細(xì)胞ZO-1合成,減少細(xì)胞內(nèi)應(yīng)力纖維數(shù)量,從而穩(wěn)定內(nèi)皮細(xì)胞間緊密連接,減少BBB通透性。這種BBB的修復(fù)作用能保護神經(jīng)組織,從而減少神經(jīng)元凋亡,促進傷后早期神經(jīng)功能恢復(fù)。第二部分 膜粘連蛋白Ⅱ通過血管再生途徑對小鼠顱腦創(chuàng)傷后遠(yuǎn)期神經(jīng)功能恢復(fù)的影響目的：評估外源性重組A2對創(chuàng)傷性顱腦損傷后長期神經(jīng)功能預(yù)后的影響,同時探討A2促進神經(jīng)功能修復(fù)的機制。方法：實驗一：外源性A2蛋白對顱腦創(chuàng)傷后遠(yuǎn)期神經(jīng)功能恢復(fù)和傷灶體積的影響通過NSS評分、轉(zhuǎn)棒實驗和水迷宮實驗分別將CCI傷后小鼠進行檢測,觀察rA2對顱腦創(chuàng)傷后神經(jīng)功能恢復(fù)的影響；對CCI傷后小鼠的組織切片進行HE染色,觀察rA2對顱腦創(chuàng)傷后傷灶體積的影響。實驗二：外源性A2蛋白對顱腦創(chuàng)傷后血管再生的影響及其機制離體培養(yǎng)內(nèi)皮細(xì)胞,檢測rA2對內(nèi)皮細(xì)胞增殖、管腔結(jié)構(gòu)形成和運動遷移的影響；通過CD31/Brdu標(biāo)記新生內(nèi)皮細(xì)胞,檢測rA2對顱腦創(chuàng)傷后內(nèi)皮細(xì)胞增殖的影響；通過靜脈注射Lectin,檢測rA2對顱腦創(chuàng)傷后功能性血管密度的影響；分離傷后皮質(zhì)微血管并進行原位酶活性檢測,比較rA2對顱腦創(chuàng)傷后血管血纖維蛋白溶酶活性的影響。實驗三：外源性A2蛋白對顱腦創(chuàng)傷后神經(jīng)再生的影響及其機制通過標(biāo)記Nestin/Brdu標(biāo)記增殖的神經(jīng)干細(xì)胞,檢測rA2對顱腦創(chuàng)傷后神經(jīng)干細(xì)胞增殖的影響；通過NeuN/Brdu標(biāo)記新生的神經(jīng)元,檢測rA2對顱腦創(chuàng)傷后神經(jīng)再生的影響；通過PSA-NCAM/Brdu標(biāo)記新生的成神經(jīng)細(xì)胞,檢測rA2對顱腦創(chuàng)傷后成神經(jīng)細(xì)胞遷移的影響；通過對傷側(cè)腦組織中蛋白質(zhì)定量,檢測rA2對顱腦創(chuàng)傷后神經(jīng)營養(yǎng)因子的影響；分離傷后皮質(zhì)微血管并提取mRNA,檢測rA2對顱腦創(chuàng)傷后血管內(nèi)皮內(nèi)神經(jīng)營養(yǎng)因子基因轉(zhuǎn)錄水平的影響。結(jié)果：實驗一：NSS評分、轉(zhuǎn)棒實驗結(jié)果證實rA2能顯著提高傷后28天內(nèi)運動相關(guān)行為學(xué)表現(xiàn)(P0.05),水迷宮實驗中rA2組小鼠的空間記憶能力明顯優(yōu)于對照組小鼠(P0.05)；HE染色證實給予rA2后傷灶體積無明顯改變(P0.05)。實驗二：離體培養(yǎng)條件下,rA2能顯著促進內(nèi)皮細(xì)胞增殖、管腔結(jié)構(gòu)形成與運動遷移能力(P0.05)；rA2能顯著增加CCI傷后7天內(nèi)海馬和傷灶周圍內(nèi)皮細(xì)胞增殖(P0.05)；傷后28天時,rA2組傷灶周圍皮質(zhì)功能性血管密度顯著高于對照組(P0.05),但海馬區(qū)血管網(wǎng)密度無明顯變化(P0.05)；rA2提高傷后7天皮質(zhì)微血管內(nèi)血纖維蛋白溶酶活性。實驗三：rA2對傷后早期SGZ和SVZ區(qū)域的神經(jīng)干細(xì)胞分裂增殖無顯著作用(P0.05),但是卻能增加后期傷灶區(qū)域新生神經(jīng)元的數(shù)量(P0.05)；rA2增加了傷后7天內(nèi)遷移至傷灶周圍以及海馬齒狀回的新生神經(jīng)元數(shù)量(P0.05)；rA2增加傷側(cè)腦組織中BDNF、VEGF的含量；分離傷后7天時小鼠腦組織皮質(zhì)微血管,rA2組微血管內(nèi)BDNF、 VEGF的mRNA轉(zhuǎn)錄水平顯著對照組(P0.05)。結(jié)論：在創(chuàng)傷性顱腦損傷后,rA2能提高微血管內(nèi)血纖維蛋白溶酶活性,從而促進傷后血管再生。同時,增生活躍的內(nèi)皮細(xì)胞能分泌更多的神經(jīng)營養(yǎng)因子,這些因子能吸引成神經(jīng)細(xì)胞沿著血管網(wǎng)走行向受傷區(qū)域遷移,到達后發(fā)育為成熟的神經(jīng)元,從而參與傷后的神經(jīng)修復(fù)重建,最終促進傷后長期神經(jīng)功能恢復(fù)。
[Abstract]:The first part of the membrane adhesion protein by protecting blood brain barrier effect on early recovery of nerve function after traumatic brain injury in mice Objective: To evaluate the effect of exogenous A2 on early prognosis of neurological function and blood brain barrier after traumatic brain injury, brain trauma of A2 as the target of treatment possibilities. Methods: experiment 1: the change of endogenous A2 expression of CCI in different time points after different cells and establish accurate cortical hit model in adult male mice, detected before and after injured at different time points (6 hours, 1 days, 3 days, 5 days, 7 days, 14 days, 21 days) the expression of A2 protein in brain tissue of the injured hemisphere with CD31, GFAP, NeuN; were labeled endothelial cells, astrocytes and neurons, changes with A2 antibody double staining detection after injury, the expression of A2 in different cell types. Experiment two: exogenous A2 protein on CCI BBB permeability Of brain edema and effects of hippocampal neurons in vitro cultured endothelial cells and establish the injury model, detection of rA2 on endothelial cell injury resistance, effect of endothelial barrier permeability and endothelial cell viability; CCI mice after injury by intravenous injection of Evans blue dye and measuring hemisphere dye content, to study the effect of rA2 on the permeability of BBB; Determination of injury by dry wet method after the brain tissue water content, to study the effect of rA2 on brain edema after cerebral injury; immunohistochemistry of CCI of hippocampus neurons were labeled and quantitative detection effect of hippocampal neural Yuan Cunhuo rA2 after injury; give away from the medium with endothelial cell conditioned body hypoxia treated neurons, by detection of rA2 endothelial cells on damaged neurons cell viability. Experiment three: the effect of exogenous A2 protein on CCI early after the recovery of neurological function and infarct volume through injury The NSS score, Wire-gripping test were used to detect CCI after injury in mice, the effect of rA2 on the effect of early recovery of nerve function after traumatic brain injury; the staining of CCI after injury in mice tissues were stained with HE, the effect of rA2 on traumatic brain injury after traumatic volume. Experiment four: the mechanism of exogenous A2 protein on brain injury the protective effect of BBB by gelatin zymography, to study the effect of rA2 on the activity of MMP-9 in brain tissue after traumatic brain injury; the quantitative protein injured side brain tissue, detection of rA2 for traumatic brain injury after VEGF, Occludin, expression of Claudin-5 and ZO-1; in vitro endothelial cell injury model, detect the effect of rA2 stress on fiber formation endothelial cells. Results: experiment one: from the 3 day after injury, the expression of A2 increased significantly (P0.05), and reached the peak at day 7 (P0.05). Since then, the expression decreased gradually, the 21 day return to the base value of contrast. Before and after injured immunohistofluorescence results before the injury of endothelial cells, almost no expression of A2 after injury in the injured side, part of the expression of A2 of endothelial cells; injury of astrocytes partially expressed A2, had bilateral activation of glial cells after injury, and the activation of glial cells can express A2; neurons expression in existing A2 injury before, after the injury did not change significantly. Experiment two: rA2 can significantly improve the resistance in endothelial cells after injury of endothelial cell (P0.05) and cell viability (P0.05), and reduce the number of endothelial cells through the FITC-dextran barrier (P0.05); the same time point not after injury (2 hours, 4 hours, 6 hours) different doses of rA2 (0.75mg/kg, 1mg/kg, 1.5mg/kg) were injected into mice by tail vein, can significantly reduce the injury of brain tissue exudation of EB (P0.05); rA2 did not significantly alter the injury status of brain edema (P0.05); rA2 can significantly reduce the injury after 7 days CA1 and CA3 area neuron loss, reduce the damage zone structure of hippocampus (P0.05); rA2 endothelial cell conditioned medium can significantly improve the hypoxic neuronal activity (P0.05). Experiment three: NSS score results confirmed that rA2 can significantly improve the exercise after injury within 7 days of behavioral performance (P0.05), rA2 group the mice in the Wire-gripping experiment showed no significant difference with the control group (P0.05); HE staining confirmed after giving rA2 injury. The volume did not change significantly (P0.05). Experiment four: rA2 had no significant effect on the 7 day after injury in mice brain tissue MMP-9 activity (P0.05); rA2 VEGF on the 7 day after injury in mice brain Occludin, and the expression of Claudin-5 had no significant effect (P0.05); rA2 ZO-1 expression was significantly increased 7 days after injury in mouse brain tissue (P0.05); the number of stress fibers after giving rA2 damaged endothelial cells decreased significantly (P0.05). Conclusion: in the early stage of traumatic brain injury, RA2 can improve the endothelial cell ZO-1 synthesis, reduce the number of cell stress fibers, thereby stabilizing endothelial tight junctions between cells, reduce the permeability of BBB. This repair BBB can protect the nerve tissue, thereby reducing neuronal apoptosis, promote early recovery of nerve function after injury. The second part film adhesion protein II through vascular regeneration effect on long-term recovery the nerve function after traumatic brain injury in mice Objective: To evaluate the effects of exogenous recombinant A2 on traumatic brain injury after long-term neurological outcome, and explore the mechanism of A2 promoting the recovery of neural function. Methods: experiment one: effects of exogenous A2 protein on long-term neurological functional recovery after traumatic brain injury and traumatic volume by NSS score, turn bar test and water maze test respectively after injury CCI mice were detected, the effect of rA2 on the recovery of nerve function after traumatic brain injury of CCI after injury; Mouse tissue sections were stained with HE, the effect of rA2 on traumatic brain injury after traumatic volume. Experiment two: the effect of exogenous A2 protein on vascular regeneration after traumatic brain injury and its mechanism in vitro cultured endothelial cells, detection of rA2 on endothelial cell proliferation, migration and lumen formation influence movement; through endothelial CD31/Brdu markers cell detection effect of rA2 on proliferation of endothelial cells after traumatic brain injury; by intravenous injection of Lectin, detection of rA2 effects on functional vascular density after traumatic brain injury; for in situ detection of enzyme activity and cortical microvascular separation after injury, to compare the effects of rA2 on vascular plasmin activity after traumatic brain injury: experiment three. Exogenous A2 protein effect on nerve regeneration after traumatic brain injury and its mechanism by marking the proliferation of neural stem cell marker Nestin/Brdu, rA2 detection of traumatic brain injury neural stem cells Effect of cell proliferation by NeuN/Brdu markers; new neurons, detection of rA2 effect on nerve regeneration after traumatic brain injury; nerve cells through PSA-NCAM/Brdu labeled newborn, detect the influence of rA2 on craniocerebral trauma after nerve cell migration; through the quantification of protein in the brain tissue of the injured side, detect the effect of rA2 on neurotrophic factor in the brain trauma; injury of cortical microvascular separation and extraction of mRNA, to study the effect of rA2 on neurotrophic factor gene expression after traumatic brain injury in vascular endothelial cells. Results: experiment one: NSS score, rotarod test results showed that rA2 showed movement within 28 days after the injury related behavior increased significantly (P0.05), space the memory ability of rA2 mice in the water maze test was better than the control group (P0.05); HE staining confirmed after giving rA2 injury. The volume did not change significantly (P0.05). Experiment two: in vitro culture. Under the condition, rA2 can significantly promote endothelial cell proliferation, lumen formation and migration ability (P0.05); rA2 within 7 days of the hippocampus and wound around the focus of endothelial cell proliferation significantly increased CCI after injury (P0.05); 28 days after injury, injury group rA2 cerebral cortex functional vascular density was significantly higher than that of the control group (P0.05), but in hippocampus of vascular density did not change significantly (P0.05); rA2 increased 7 days after injury of cortical microvascular plasmin activity. Experiment three: rA2 had no significant effect on SGZ and SVZ cells in the early region of neural stem proliferation after injury (P0.05), but the number can increase in post traumatic area of new neurons (P0.05); rA2 increased 7 days after injury to the wound around the focus and migration of newborn neurons in the hippocampal dentate gyrus (P0.05); the number of rA2 increased BDNF injury in the brain tissues, the content of VEGF; the separation of 7 days after the injury in brain tissue of small rat cortical microvascular, Group rA2 microvascular BDNF, VEGF transcription of mRNA significantly in control group (P0.05). Conclusion: in traumatic brain injury, rA2 can improve the microvascular plasmin activity, thereby promoting vascular regeneration after injury. At the same time, hyperplasia of endothelial cells can secrete neurotrophic factors more, these factors can attract into neural cells along the vascular network to go after the arrival of the injured area migration, the formation of mature neurons, and thus participate in the repair and reconstruction of nerve injury, and ultimately promote the recovery of nerve function after long-term injury.

【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2015
【分類號】：R651.15

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6 江基堯;;提高我國顱腦創(chuàng)傷治療水平的幾個關(guān)鍵問題[J];臨床神經(jīng)外科雜志;2005年04期

7 陳江利;何玉領(lǐng);楊剛;;顱腦創(chuàng)傷后高滲高血糖非酮癥狀昏迷的臨床研究[J];浙江創(chuàng)傷外科;2006年02期

8 劉劍波;劉世玉;丁冬梅;;顱腦創(chuàng)傷后進展型出血性損傷的臨床特點及原因探討[J];中華神經(jīng)外科疾病研究雜志;2007年03期

9 桑潺;張立杰;劉孝琴;;瀕死型顱腦創(chuàng)傷31例臨床分析[J];基層醫(yī)學(xué)論壇;2008年34期

10 何亮;楊天明;;顱腦創(chuàng)傷無創(chuàng)監(jiān)測技術(shù)研究進展[J];東南大學(xué)學(xué)報(醫(yī)學(xué)版);2008年02期

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