本文選題：腦出血 + Caspase-7　； 參考：《右江民族醫(yī)學院》2017年碩士論文

【摘要】：目的:通過觀察在瑞舒伐他汀干預下大鼠實驗性腦出血(Intracerebral hemorrhage,ICH)血腫周圍腦組織中半胱氨酸蛋白酶3(cysteinylaspartate specific proteinases 3,Caspase-3)、半胱氨酸蛋白酶7(cysteinylaspartate specific proteinases 7,Caspase-7)和凋亡抑制蛋白1(cellular inhibitor of apoptosis proteins 1,c-IAP-1)的表達變化,探討瑞舒伐他汀在腦出血發(fā)生后可能出現的神經保護作用及其機制,對臨床用藥起到一定指導作用。方法:(1)將60只SD大鼠按照隨機分組的方法分為假手術組(A組,20只),腦出血組(B組,20只),瑞舒伐他汀干預組(C組,20只)。每組分成6h、24h、72h、5d四個時間點,每個時間點使用5只大鼠進行造模并實驗。采用自體凝固血注入右側尾狀核法建立腦出血模型。(2)采用Garcia法對三組大鼠術后4個時間點分別進行神經缺損評分。(3)免疫組化法對三組大鼠血腫周圍腦組織切片染色并在顯微鏡下觀察分析。(4)RT-qPCR技術測定三組大鼠腦出血術后4個時間點血腫周圍腦組織Caspase-3,-7及c-IAP-1表達狀況。結果:(1)Garcia評分評估發(fā)現6小時時間點腦出血組和瑞舒伐他汀干預組相比差異無統(tǒng)計學意義,其余三個時間點瑞舒伐他汀干預組(C組)神經缺損情況較腦出血組(B組)減輕,P0.05,有統(tǒng)計學意義。兩組均在72h神經缺損癥狀達到峰值,之后癥狀緩解。假手術組(A組)與其余兩組在術后4個時間點相比發(fā)現假手術組(A組)神經缺損較輕,神經功能遠高于其余兩組,差異均有統(tǒng)計學意義。(2)免疫組化法染色后顯微鏡下可觀察到假手術組(A組)4個時間點腦出血后c-IAP-1和Caspase-3,-7陽性細胞少量表達,腦出血組(B組)和瑞舒伐他汀干預組(C組)較假手術組(A組)每個時間點陽性細胞均出現顯著的增高。除腦出血后6小時這一時間點外,其余各個時間點的瑞舒伐他汀干預組(C組)要比腦出血模型組(B組)c-IAP-1陽性細胞表達增多,Caspase-3,-7陽性細胞表達減少。瑞舒伐他汀能降低Caspase-3,-7及提高c-IAP-1水平(3)RT-qPCR法顯示,假手術組組與腦出血模型組和瑞舒伐他汀組組術后各個時間點相比c-IAP-1及Caspase-3,-7表達水平低。6小時時間點腦出血組和瑞舒伐他汀干預組相比差異無統(tǒng)計學意義,其余時間點之間腦出血組和瑞舒伐他汀干預組相比,c-IAP-1表達降低,Caspase-3,-7表達增高,差異有統(tǒng)計學意義。結論:(1)瑞舒伐他汀可以降低腦出血后神經功能缺損癥狀。(2)瑞舒伐他汀能夠抑制Caspase-3和Caspase-7活化,進而提高c-IAP-1的表達,c-IAP-1反作用于Caspase-3和Caspase-7,從而進一步抑制Caspase-3和Caspase-7表達。提示瑞舒伐他汀能夠降低由細胞凋亡影響引起的繼發(fā)性的腦損傷,對神經功能起到一定的保護作用。
[Abstract]:Objective: to observe the changes of the expression of Caspase-3, 7(cysteinylaspartate specific proteinases 7caspase-7 and 1(cellular inhibitor of apoptosis proteins 1c-IAP-1 in the perihematoma tissue of rat experimental intracerebral hemorrhage (ICH) induced by recuvastatin, and to observe the expression of 3(cysteinylaspartate specific proteinases 3 Caspase-3, 7(cysteinylaspartate specific proteinases 7caspase-7 and 1(cellular inhibitor of apoptosis proteins 1c-IAP-1.To explore the neuroprotective effect and mechanism of resuvastatin in patients with cerebral hemorrhage.Methods 60 Sprague-Dawley rats were randomly divided into sham-operated group (n = 20), intracerebral hemorrhage group (n = 20) and control group (n = 20).The rats in each group were divided into four time points (6 h, 24 h, 72 h and 5 d), and 5 rats were used at each time point to model and experiment.Establishment of intracerebral hemorrhage model by injecting autologous coagulation blood into right caudate nucleus. (2) Garcia method was used to evaluate the neurological defect of rats at 4 time points after operation.) Immunohistochemical method was used to stain the brain tissue sections around hematoma in three groups of rats.The expression of Caspase-3 + -7 and c-IAP-1 in brain tissue around intracerebral hemorrhage in three groups were detected by RT-PCR at four time points after intracerebral hemorrhage.Results there was no significant difference between the 6 hour cerebral hemorrhage group and the recuvastatin intervention group.At the other three time points, the nerve defect in the control group was significantly lower than that in the cerebral hemorrhage group (P 0.05).The symptoms of nerve defect reached the peak at 72 hours in both groups, and then relieved.Compared with the other two groups at 4 time points after operation, the sham operation group (group A) showed that the nerve defect in group A was lighter and the nerve function was much higher than that in the other two groups.The differences were statistically significant. (2) the expression of c-IAP-1 and Caspase-3 + -7 were observed under microscope in sham-operation group (group A) after intracerebral hemorrhage at four time points after immunohistochemical staining.The positive cells in group B (group B) and group C (group C) were significantly higher than those in group A (sham operation group) at each time point.Except for the time point of 6 hours after intracerebral hemorrhage, the expression of c-IAP-1 positive cells increased and the expression of Caspase-3 + -7 was decreased in the other time points of Risuvastatin intervention group (group C) than that in the model group of intracerebral hemorrhage (group B).Rosuvastatin could decrease Caspase-3 -7 and increase the level of c-IAP-1 by 3RT-qPCR.There was no significant difference in the expression of c-IAP-1 and Caspase-3 ~ (-7) between the sham operation group and the cerebral hemorrhage model group and the rosuvastatin group at different time points after operation compared with those of the cerebral hemorrhage group and the rosuvastatin intervention group.The expression of c-IAP-1 in ICH group and Risuvastatin group was significantly lower than that in control group at other time points.Conclusion Risuvastatin can reduce the neurological deficit symptoms after intracerebral hemorrhage. Resuvastatin can inhibit the activation of Caspase-3 and Caspase-7, and then increase the expression of c-IAP-1. C-IAP-1 counteracts Caspase-3 and Caspase-7, thus further inhibiting the expression of Caspase-3 and Caspase-7.These results suggest that rosuvastatin can reduce the secondary brain injury induced by apoptosis and play a protective role in neurologic function.
【學位授予單位】：右江民族醫(yī)學院
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R743.34

【參考文獻】

相關期刊論文 前10條

1 羅崗;黃yN諾;王建軍;趙志軍;王新春;李鳳仙;王曉雪;王華;許宏俠;蘇亞麗;;洋蔥黃酮類提取物對大鼠腦出血后血腫周圍活化小膠質細胞及炎癥因子的抑制作用[J];中國中西醫(yī)結合雜志;2016年07期

2 官念;吳碧華;劉黎明;楊云鳳;李永莉;張蓉;任麗君;劉琳;;腦出血病因及相關機制的研究進展[J];中華老年心腦血管病雜志;2016年06期

3 再努熱木·艾則孜;熱娜古麗·艾則孜;阿得力艾山;阿不力克木;王小英;高冉冉;艾斯卡爾·沙比提;;阿托伐他汀對冠心病大鼠心肌細胞的凋亡及caspase-12表達的影響[J];現代生物醫(yī)學進展;2015年32期

4 易芳;許宏偉;;他汀類藥物治療腦出血的研究進展[J];中華腦科疾病與康復雜志(電子版);2015年05期

5 史曉靜;王高頻;陶貴周;;阿托伐他汀通過抑制NF-κB對抗大鼠缺血再灌注心肌炎癥反應和凋亡的機制[J];臨床心血管病雜志;2015年07期

6 梁瑞;吳鶴;戚基萍;;活化的小膠質細胞在腦出血后的作用[J];現代醫(yī)學;2015年02期

7 李超;李明;趙杰;陳靜;;膜死亡受體介導肺泡巨噬細胞凋亡的信號轉導途徑[J];工業(yè)衛(wèi)生與職業(yè)病;2014年02期

8 王新;李明軍;張坤;崔大勇;鄔巍;;腦出血與小膠質細胞介導的炎癥相關性[J];中國老年學雜志;2013年13期

9 涂征艷;石碩;李玉梅;;化滯柔肝顆粒聯合瑞舒伐他汀鈣治療脂肪肝的療效觀察[J];中國醫(yī)藥科學;2012年23期

10 魏亞芬;臧召霞;劉志強;殷萍;劉永丹;;實驗性腦出血大鼠腦內Caspase-3mRNA的表達作用研究[J];中華腦血管病雜志(電子版);2012年06期

相關會議論文 前1條

1 嚴鋒;張立新;陳敬寅;王林;陳高;;內質網應激通過自噬途徑對蛛網膜下腔出血后早期腦損傷發(fā)揮神經保護作用[A];2014浙江省神經外科學學術年會論文匯編[C];2014年

相關博士學位論文 前1條

1 王惠樞;右美托咪定對嚴重燙傷大鼠心肌損傷的影響及其機制的研究[D];南方醫(yī)科大學;2014年

相關碩士學位論文 前10條

1 曾雁雁;高壓氧預處理對脊髓損傷大鼠神經元Caspases凋亡通路的影響[D];廣州中醫(yī)藥大學;2016年

2 劉謙;黃連素通過抑制細胞凋亡和自噬減輕大鼠肝缺血再灌注損傷的研究[D];揚州大學;2016年

3 王圓媛;可控活化的Caspase-3/7的非凋亡功能在乳腺癌發(fā)生發(fā)展中的作用[D];天津醫(yī)科大學;2015年

4 劉雁;辛伐他汀預處理對神經源性肺水腫大鼠肺微血管內皮細胞Bcl-2和Bax的影響[D];南華大學;2015年

5 鄧婷;依達拉奉對大鼠腦出血后神經細胞凋亡及Caspase-3、PARP-1表達影響的實驗研究[D];四川醫(yī)科大學;2015年

6 朱文麗;大鼠實驗性腦出血急性期Notch1與NF-κB的表達變化及他汀的干預作用[D];中南大學;2014年

7 祝琳;血清鐵蛋白、尿酸水平與腦出血患者預后的關系[D];河北醫(yī)科大學;2014年

8 張政軍;瑞舒伐他汀對高同型半胱氨酸血癥大鼠主動脈Bcl-2與Bax表達的影響的研究[D];寧夏醫(yī)科大學;2013年

9 曾昭;瑞舒伐他汀對大鼠實驗性腦出血腦組織Caspase-9和C-IAP-1的表達變化影響的研究[D];中南大學;2012年

10 吳忠林;瑞舒伐他汀對急性心肌梗死大鼠心肌細胞凋亡與Fas、Caspase-3表達的影響[D];鄭州大學;2012年

，

本文編號：1768092