本文關(guān)鍵詞：載脂蛋白E短肽COG1410對蛛網(wǎng)膜下腔出血后早期腦水腫的影響　出處：《西南醫(yī)科大學(xué)》2016年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 蛛網(wǎng)膜下腔出血 載脂蛋白E短肽 水通道蛋白4 腦水腫 早期腦損傷

【摘要】：目的:探討載脂蛋白E短肽COG1410對小鼠實驗性蛛網(wǎng)膜下腔出血(subarachnoid hemorrhage,SAH)后早期腦損傷(early brain injury,EBI)中腦水腫、運動功能和水通道蛋白4(AQP-4)的影響。方法:108只C57BL/6J小鼠分成假手術(shù)對照組(sham組)36只、生理鹽水組(SAH+生理鹽水組)36只、治療組(SAH+COG1410組)36只,分別采用血管內(nèi)穿刺法建立SAH模型。36只小鼠采用類似血管內(nèi)穿刺法但不刺破頸內(nèi)動脈建成假手術(shù)對照組(sham組);36只小鼠采用血管內(nèi)穿刺法建成SAH模型,并在1d、2d、3d時經(jīng)尾靜脈向小鼠體內(nèi)注入生理鹽水建成生理鹽水組(SAH+生理鹽水組);36只小鼠采用血管內(nèi)穿刺法建成SAH模型在1d、2d、3d時經(jīng)尾靜脈向小鼠體內(nèi)注入相同劑量的載脂蛋白E短肽COG1410建成治療組(SAH+COG1410組)。隨機選取6只假手術(shù)對照組小鼠、6只生理鹽水組小鼠、6只治療組小鼠用于觀察小鼠1d、2d、3d的運動功能變化。隨機選取6只假手術(shù)對照組小鼠、6只生理鹽水組小鼠、6只治療組小鼠采用干濕質(zhì)量法測定小鼠1d、2d、3d的腦組織含水量的變化。隨機選取6只假手術(shù)對照組小鼠、6只生理鹽水組小鼠、6只治療組小鼠采用免疫組化法測定小鼠1d、2d、3d的腦組織表達(dá)AQP-4陽性細(xì)胞數(shù)。隨機選取6只假手術(shù)對照組小鼠、6只生理鹽水組小鼠、6只治療組小鼠采用酶聯(lián)免疫吸附法(ELISA)測定小鼠1d、2d、3d的腦組織AQP-4蛋白含量。隨機選取6只假手術(shù)對照組小鼠、6只生理鹽水組小鼠、6只治療組小鼠采用實時定量PCR測定小鼠1d、2d、3d的腦組織AQP-4 mRNA的變化。結(jié)果:SAH后生理鹽水組(SAH+生理鹽水組)和治療組(SAH+COG1410組)1d、2d、3d神經(jīng)功能損傷嚴(yán)重性評分均明顯高于假手術(shù)對照組(sham組)所對應(yīng)相應(yīng)時間點的神經(jīng)功能損傷嚴(yán)重性評分,且兩者之間差異有統(tǒng)計學(xué)意義(P0.05);生理鹽水組(SAH+生理鹽水組)1d、2d、3d神經(jīng)功能損傷嚴(yán)重性評分均明顯高于治療組(SAH+COG1410組)所對應(yīng)相應(yīng)時間點的神經(jīng)功能損傷嚴(yán)重性評分,且兩者之間差異有統(tǒng)計學(xué)意義(P0.05);小鼠在SAH后神經(jīng)功能損傷嚴(yán)重性評分在1d時明顯增加,2d時達(dá)到高峰,之后逐漸下降。SAH后生理鹽水組(SAH+生理鹽水組)和治療組(SAH+COG1410組)1d、2d、3d腦組織含水量均明顯高于假手術(shù)對照組(sham組)所對應(yīng)相應(yīng)時間點的腦組織含水量,且差異有統(tǒng)計學(xué)意義(P0.05);生理鹽水組(SAH+生理鹽水組)1d、2d、3d腦組織含水量均明顯高于治療組(SAH+COG1410組)所對應(yīng)相應(yīng)時間點的腦組織含水量,且兩者之間差異有統(tǒng)計學(xué)意義(P0.05);小鼠在SAH后腦組織含水量在1 d時明顯增加,2d時達(dá)到高峰,之后逐漸下降。SAH后生理鹽水組(SAH+生理鹽水組)和治療組(SAH+COG1410組)1d、2d、3d腦組織AQP4蛋白含量均明顯高于假手術(shù)對照組(sham組)所對應(yīng)相應(yīng)時間點的腦組織AQP4蛋白含量,且差異有統(tǒng)計學(xué)意義(P0.05);生理鹽水組(SAH+生理鹽水組)1d、2d、3d腦組織AQP4蛋白含量均明顯高于治療組(SAH+COG1410組)所對應(yīng)相應(yīng)時間點的腦組織AQP4蛋白含量,且兩者之間差異有統(tǒng)計學(xué)意義(P0.05);小鼠在SAH后腦組織AQP4蛋白含量在1 d時明顯增加,2d時達(dá)到高峰,之后逐漸下降。SAH后生理鹽水組(SAH+生理鹽水組)和治療組(SAH+COG1410組)1d、2d、3d腦組織AQP4陽性細(xì)胞數(shù)均明顯高于假手術(shù)對照組(sham組)所對應(yīng)相應(yīng)時間點的腦組織AQP4陽性細(xì)胞數(shù),且差異有統(tǒng)計學(xué)意義(P0.05);生理鹽水組(SAH+生理鹽水組)1d、2d、3d腦組織AQP4陽性細(xì)胞數(shù)均明顯高于治療組(SAH+COG1410組)所對應(yīng)相應(yīng)時間點的腦組織AQP4陽性細(xì)胞數(shù),且兩者之間差異有統(tǒng)計學(xué)意義(P0.05);小鼠在SAH后腦組織AQP4陽性細(xì)胞數(shù)在1d時明顯增加,2d時達(dá)到高峰,之后逐漸下降。SAH后生理鹽水組(SAH+生理鹽水組)和治療組(SAH+COG1410組)1d、2d、3d腦組織AQP4mRNA表達(dá)量均明顯高于假手術(shù)對照組(sham組)所對應(yīng)相應(yīng)時間點的腦組織AQP4mRNA表達(dá)量,且差異有統(tǒng)計學(xué)意義(P0.05);生理鹽水組(SAH+生理鹽水組)1d、2d、3d腦組織AQP4mRNA表達(dá)量均明顯高于治療組(SAH+COG1410組)所對應(yīng)相應(yīng)時間點的腦組織AQP4mRNA表達(dá)量,且兩者之間差異有統(tǒng)計學(xué)意義(P0.05);小鼠在SAH后腦組織AQP4mRNA表達(dá)量在1 d時明顯增加,2d時達(dá)到高峰,之后逐漸下降。結(jié)論:載脂蛋白E短肽COG1410可能通過抑制AQP-4的過表達(dá)緩解EBI中的腦水腫。
[Abstract]:Objective: To investigate the effect of apolipoprotein E peptide COG1410 on mice with experimental subarachnoid hemorrhage (subarachnoid hemorrhage, SAH) after early brain injury (early brain, injury, EBI) of brain edema, and motor function of aquaporin 4 (AQP-4) effect. Methods: 108 C57BL/6J mice were divided into sham operation group (sham group 36), saline group (saline group SAH+ = 36), treatment group (group SAH+COG1410) 36, SAH models were established in.36 mice by using similar endovascular puncture but not puncture of internal carotid artery into the sham operation group by endovascular puncture (sham group); 36 mice with vascular in the puncture built SAH model, and in 1D, 2D, 3D into the tail vein of mice injected saline into saline group (SAH+ saline group); 36 mice by endovascular puncture method to build SAH model in 1D, 2D, 3D by intravenous injection to mice. The same dose of apolipoprotein E peptide COG1410 into the treatment group (SAH+COG1410 group). 6 rats were randomly selected in sham control mice, 6 mice in the control group, 6 treatment group were used to observe the changes of mouse 1D, 2D, 3D's motion function. Randomly selected 6 rabbits in sham control mice, 6 only the mice in the control group, 6 mice treated by dry wet weight method for the determination of mouse 1D, 2D, 3D changes the water content of the brain tissue. Randomly selected 6 rabbits in sham control mice, 6 mice in the control group, 6 mice treated with immunohistochemical determination of 1D mice, 2D expression the number of AQP-4 positive cells in 3D brain tissue. Randomly selected 6 rabbits in sham control mice, 6 mice in the control group, 6 mice treated by enzyme linked immunosorbent assay (ELISA) determination of mouse 1D, 2D, 3D of brain tissue AQP-4 protein content. Randomly selected 6 rabbits sham operation control group mice. Only 6 students The mice in the control group and treatment group, 6 mice were determined by real-time quantitative 1D, PCR 2D, 3D AQP-4 mRNA changes in brain tissue. Results: SAH after saline group (saline group SAH+) and treatment group (SAH+COG1410 group) 1D, 2D, 3D nerve function injury severity score were significantly higher than that of the sham operation control group (Group sham) corresponding to the corresponding time points of the nerve function injury severity score, there were statistically significant differences between them (P0.05); saline group (saline group SAH+) 1D, 2D, 3D nerve function injury severity score were significantly higher than the treatment group (group SAH+COG1410) corresponding to at the same time the neurological injury severity score, there were statistically significant differences between them (P0.05); mice in SAH after nerve injury severity score increased significantly at 1D, peaked at 2D, then gradually decreased after.SAH under saline group (saline SAH+ Group) and treatment group (SAH+COG1410 group) 1D, 2D, 3D and brain water content were significantly higher than those in sham control group (Group sham) corresponding to the corresponding time points of the water content of brain tissue, and the difference was statistically significant (P0.05); saline group (saline group SAH+) 1D, 2D, 3D in the brain the tissue water content were significantly higher than the treatment group (group SAH+COG1410) corresponding to the corresponding time points of the water content of brain tissue, there were statistically significant differences between them (P0.05); SAH in mouse brain tissue water content at 1 D was significantly increased, reached the peak at 2D, then gradually decreased after.SAH under saline group (SAH+ the physiological saline group) and treatment group (SAH+COG1410 group) 1D, 2D, AQP4 protein content of 3D in brain tissue were significantly higher than those in sham control group (Group sham) corresponding to the corresponding time points of brain tissue AQP4 protein content, and the difference was statistically significant (P0.05); saline group (saline group 1D, SAH+) 2D, 3D brain AQP4 protein content were significantly higher than the treatment group (group SAH+COG1410) corresponding to the corresponding time points of brain tissue AQP4 protein content, there were statistically significant differences between them (P0.05); the content of AQP4 protein in SAH mouse brain tissue at 1 D significantly increased, reached the peak at 2D, then gradually decreased in saline group after.SAH (SAH+ saline group) and treatment group (SAH+COG1410 group) 1D, 2D, AQP4 the number of 3D positive cells in brain tissue were significantly higher than those in sham control group (Group sham) corresponding to the number of AQP4 positive cells in brain tissue at different time points, and the difference was statistically significant (P0.05); saline group (saline SAH+ group 1D, 2D, AQP4) the number of 3D positive cells in brain tissue were significantly higher than the treatment group (group SAH+COG1410) corresponding to the number of AQP4 positive cells in brain tissue at the same time, there were statistically significant differences between them (P0.05); SAH in mice brain tissue AQP4 positive The number of cells in 1D was significantly increased, reached the peak at 2D, then decreased gradually after.SAH saline group (SAH+ saline group) and treatment group (SAH+COG1410 group) 1D, 2D, 3D in brain tissue of AQP4mRNA expression was significantly higher than that in the sham operation group (Group sham) corresponding to the corresponding time points of the brain tissue AQP4mRNA the expression, and the difference was statistically significant (P0.05); saline group (saline group SAH+) 1D, 2D, 3D in brain tissue of AQP4mRNA expression was significantly higher than the treatment group (group SAH+COG1410) corresponding to the corresponding time points of the expression of AQP4mRNA in brain tissue, there were statistically significant differences between them (P0.05); mice the expression of SAH in brain tissue AQP4mRNA content at 1 D was significantly increased, reached the peak at 2D, then gradually decreased. Conclusion: apolipoprotein E peptide COG1410 EBI may alleviate cerebral edema by inhibiting the expression of AQP-4.

【學(xué)位授予單位】：西南醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2016
【分類號】：R743.35

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