本文選題：重組人促紅細(xì)胞生成素 + 腦出血　； 參考：《青島大學(xué)》2017年碩士論文

【摘要】：背景:隨著人口老齡化程度的加速,腦血管病,尤其是腦出血,成為常見的危害人類身體健康的嚴(yán)重疾病[1]。該病具有發(fā)病急、進(jìn)展快、致殘率高、致死率高、并發(fā)癥多等特點(diǎn)[2,3],截止目前為止,該病治療方法較為局限,后期并發(fā)癥發(fā)生率依然較高[4]。但通過科研人員在對(duì)腦出血發(fā)病機(jī)制的研究中也取得了一定的進(jìn)展。促紅細(xì)胞生成素(erythropoietin,EPO)是由肝臟和腎臟分泌的一種激素樣物質(zhì),用于調(diào)節(jié)血細(xì)胞生成的一類細(xì)胞因子[5]。重組人促紅細(xì)胞生成素(rhEPO)已規(guī)范生產(chǎn)。EPO的神經(jīng)保護(hù)作用使其成為一個(gè)研究熱點(diǎn),其神經(jīng)保護(hù)作用開始被廣泛研究[6,7]。EPO治療腦血管病的重要機(jī)制之一是保護(hù)神經(jīng)元,改善神經(jīng)元損傷。實(shí)驗(yàn)研究報(bào)道,EPO能夠提高腦缺血患者的神經(jīng)功能[8],但是EPO在腦出血中的研究較少,而且其具體作用機(jī)制不是很清楚,本課題探討重組人促紅細(xì)胞生成素rhEPO是否具有腦出血后神經(jīng)系統(tǒng)保護(hù)作用及其相應(yīng)機(jī)制。方法:將8周齡的Wistar雄性大鼠30只隨機(jī)分3組(每組10只),組別為假手術(shù)組、腦出血ICH組、rhEPO治療組,腦出血組大鼠進(jìn)行ICH造模,假手術(shù)組除不注血外,其余步驟同ICH組,rhEPO組術(shù)后5分鐘給予腹腔注射rhEPO,所有動(dòng)物24小時(shí)后進(jìn)行神經(jīng)功能學(xué)評(píng)分,收集大鼠腦組織,利用原位缺口末端標(biāo)記法檢測(cè)神經(jīng)細(xì)胞凋亡的變化;采用免疫組織化學(xué)SP法檢測(cè)凋亡蛋白Caspase3表達(dá);并采用Real-time PCR和Western blot檢測(cè)磷酸化JAK2、磷酸化STAT5基因和蛋白表達(dá)情況。結(jié)果:手術(shù)建立腦出血模型后24小時(shí)進(jìn)行神經(jīng)功能評(píng)分。按Longa5分制標(biāo)準(zhǔn)判定,ICH組4只評(píng)價(jià)為1分,3只評(píng)價(jià)為2分,2只評(píng)價(jià)為3分;rhEPO組治療后,5只評(píng)價(jià)為1分,2只評(píng)價(jià)為2分,1只評(píng)價(jià)為3分。說明rhEPO可以改善大鼠腦出血后神經(jīng)元損傷,恢復(fù)神經(jīng)功能。與假手術(shù)組相比,ICH模型組和rhEPO治療組中神經(jīng)元凋亡細(xì)胞及Caspase3的蛋白表達(dá)陽(yáng)性細(xì)胞數(shù)明顯增多(P0.05),而rhEPO組中凋亡細(xì)胞與ICH模型組相比明顯減少(P0.05);與假手術(shù)組相比,ICH模型組和rhEPO組中JAK2和STAT5的蛋白表達(dá)和m RNA表達(dá)顯著上升(P0.05),與ICH模型組相比,rhEPO組中JAK2和STAT5的蛋白表達(dá)和m RNA表達(dá)顯著降低,差異均有統(tǒng)計(jì)學(xué)意義(P0.05)。結(jié)論:外源性rhEPO可以對(duì)腦出血后神經(jīng)細(xì)胞起到保護(hù)作用,其作用機(jī)制是通過調(diào)節(jié)凋亡相關(guān)蛋白caspase以及JAK2/STAT5信號(hào)改善大鼠腦出血后神經(jīng)元損傷。
[Abstract]:Background: with the acceleration of population aging, cerebrovascular disease, especially intracerebral hemorrhage, has become a common serious disease endangering human health [1].The disease is characterized by rapid onset, rapid progress, high disability rate, high fatality rate and many complications. Up to now, the treatment of the disease is limited, and the incidence of late complications is still high [4].However, some progress has been made in the study of the pathogenesis of intracerebral hemorrhage by researchers.Erythropoietin erythropoietin (EPO) is a hormone like substance secreted by the liver and kidney, which is used to regulate the production of blood cells [5].Recombinant human erythropoietin rhEPO (rhEPO) has made the neuroprotective effect of .EPO a hot research topic, and its neuroprotective effect has been widely studied. One of the important mechanisms for the treatment of cerebrovascular diseases is the protection of neurons, which is one of the important mechanisms for the treatment of cerebrovascular diseases by recombinant human erythropoietin (rhEPO).Improve neuronal injury.It is reported that EPO can improve the neurological function of cerebral ischemia patients [8], but there are few studies on the role of EPO in cerebral hemorrhage, and its mechanism is not very clear.The purpose of this study was to investigate whether recombinant human erythropoietin (rhEPO) has neuroprotective effect after intracerebral hemorrhage (ICH) and its mechanism.Methods: thirty 8-week-old male Wistar rats were randomly divided into 3 groups (10 rats in each group, sham-operated group, ICH group, intracerebral hemorrhage group, intracerebral hemorrhage group). The rats in the sham-operation group were treated with ICH, and no blood was injected into the sham-operation group.The other steps were the same as that in the ICH group. All the animals were given intraperitoneal injection of rhEPO 5 minutes after operation. After 24 hours, the neurological function scores were collected and the changes of neuronal apoptosis were detected by in situ Nick end labeling method.Immunohistochemical SP method was used to detect the expression of apoptotic protein Caspase3, and Real-time PCR and Western blot were used to detect the expression of phosphorylated JAK2, phosphorylated STAT5 gene and protein.Results: the neurological function was evaluated 24 hours after the establishment of ICH model.According to the standard of Longa5 score, 4 patients in ICH group were evaluated as 1 minute, 3 as 2 minutes, 2 as 3 minutes, 2 as 1 minute, 2 as 2 minutes and 1 as 3 points after treatment, 5 cases were evaluated as 1 minute, 2 cases were evaluated as 2 minutes and 1 case was evaluated as 3 points.The results showed that rhEPO could improve the neuronal injury and restore the neural function after intracerebral hemorrhage in rats.Compared with sham operation group and rhEPO group, the number of neuronal apoptotic cells and the expression of Caspase3 protein were significantly increased in rhEPO group, while the number of apoptotic cells in rhEPO group was significantly lower than that in ICH model group, and that in sham operation group was significantly lower than that in sham operation group, while the expression of Caspase3 protein in rhEPO group was significantly lower than that in ICH model group, while that in rhEPO group was significantly lower than that in ICH model group.The protein expression of JAK2 and STAT5 and the expression of m RNA in group A and rhEPO were significantly increased (P 0.05), and the protein expression of JAK2 and STAT5 and the expression of m RNA in group B were significantly lower than those in group B (ICH model group).The difference was statistically significant (P 0.05).Conclusion: exogenous rhEPO can protect neurons from intracerebral hemorrhage by regulating apoptosis-related protein caspase and JAK2/STAT5 signal to improve neuronal injury after intracerebral hemorrhage.
【學(xué)位授予單位】：青島大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R743.34

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 Guang-qiang Hu;Xi Du;Yong-jie Li;Xiao-qing Gao;Bi-qiong Chen;Lu Yu;;Inhibition of cerebral ischemia/reperfusion injuryinduced apoptosis: nicotiflorin and JAK2/STAT3 pathway[J];Neural Regeneration Research;2017年01期

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本文編號(hào)：1762209