發(fā)布時(shí)間：2018-03-08 01:35

  本文選題：蛛網(wǎng)膜下腔出血　切入點(diǎn)：早期腦損傷　出處：《浙江大學(xué)》2015年碩士論文　論文類(lèi)型：學(xué)位論文

【摘要】：目的： 早期腦損傷(Early brain injury, EBI)在蛛網(wǎng)膜下腔出血(subarachnoid hemorrhage, SAH)發(fā)病機(jī)制中扮演著重要作用。神經(jīng)元凋亡是參與SAH后EB]的重要病理機(jī)制。前期研究表明,富氫生理鹽水(Hydrogen-rich Saline, HS)能抑制神經(jīng)元凋亡,從而減輕SAH后的EBI。氫氣在EBI中具體的抗凋亡效應(yīng)的分子機(jī)制至今仍未被闡明。在本研究中,我們旨在闡述氫氣是否能通過(guò)調(diào)節(jié)Akt/GSK3β信號(hào)通路的活性來(lái)抑制神經(jīng)元凋亡,進(jìn)而減輕SAH后的EBI。 方法： Sprague-Dawley大鼠(n=85)被隨機(jī)分成以下幾組：假手術(shù)組(n=17), SAH組(n=17), SAH+生理鹽水組(n=17),SAH+HS組(n=17)和SAH+HS+Ly294002組(n=17)。HS或者等量的生理鹽水立即被注射到術(shù)后的大鼠體內(nèi),8小時(shí)后重復(fù)注射一次。P13K抑制劑Ly294002用來(lái)抑制上述的信號(hào)通路。SAH后24小時(shí)進(jìn)行死亡率計(jì)算、神經(jīng)功能評(píng)分及SAH分級(jí)。應(yīng)用Western blot量化分析Akt、pAkt、GSK3β、pGSK3β和caspase-3等蛋白。通過(guò)末端脫氧核糖核酸染色法(TUNEL)和神經(jīng)元特異性核蛋白(NeuN)來(lái)檢測(cè)神經(jīng)元凋亡。用免疫組化來(lái)闡明神經(jīng)元凋亡和pAkt或者pGSK3β之間的關(guān)系。 結(jié)果： HS能顯著地減少神經(jīng)元凋亡,從而改善SAH大鼠的神經(jīng)功能缺失。HS能使在神經(jīng)元表達(dá)的pAkt和pGSK3β水平顯著地上調(diào)了。除此之外,通過(guò)HS的治療,caspase-3顯著下調(diào)。通過(guò)pAkt和TUNEL的染色顯示了pAkt陽(yáng)性細(xì)胞和TUNEL陽(yáng)性細(xì)胞的共同表達(dá)。P13K抑制劑Ly294002能夠抑制HS帶來(lái)的良好效應(yīng)。 結(jié)論： HS通過(guò)激活A(yù)kt/GSK3β通路,能夠減輕EBI的神經(jīng)元凋亡,改善SAH后的神經(jīng)功能預(yù)后。
[Abstract]:Objective:. Early brain injuryplays an important role in the pathogenesis of subarachnoid hemorrhage (Sah). Neuronal apoptosis is an important pathological mechanism involved in EB after SAH. Hydrogen-rich Salineine (HS) can inhibit neuronal apoptosis and alleviate EBI. the molecular mechanism of anti-apoptotic effect of hydrogen in EBI has not been elucidated. We aim to investigate whether hydrogen can inhibit neuronal apoptosis by regulating the activity of Akt/GSK3 尾 signaling pathway, and then reduce the EBI after SAH. Methods:. Sprague-Dawley rats were randomly divided into the following groups: sham-operated group (n = 17) and SAH HS Ly294002 group (n = 17) and SAH HS Ly294002 group (n = 17) and SAH HS Ly294002 group (n = 8 h after injection). P13K inhibitor Ly294002 was used to inhibit the above signaling pathway. SAH was used to calculate the mortality rate 24 hours later. Nerve function score and SAH grade. Western blot was used to quantitatively analyze the proteins, such as Aktaphane, GSK3 尾, pGSK3 尾 and caspase-3. Apoptosis of neurons was detected by terminal deoxyribonucleic acid staining (Tunel) and neuron specific nucleoprotein (Neun). The neuronal apoptosis was elucidated by immunohistochemistry. The relationship between meta apoptosis and pAkt or pGSK3 尾. Results:. HS can significantly reduce neuronal apoptosis, thereby improving neural function loss in SAH rats. HS can significantly up-regulate the expression of pAkt and pGSK3 尾 in neurons. Through the treatment of HS, caspase-3 was significantly down-regulated. PAkt and TUNEL staining showed that the co-expression of pAkt positive cells and TUNEL positive cells. P13K inhibitor Ly294002 could inhibit the good effect of HS. Conclusion:. HS can attenuate the neuronal apoptosis of EBI by activating Akt/GSK3 尾 pathway and improve the prognosis of neural function after SAH.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類(lèi)號(hào)】：R651.15

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