發(fā)布時(shí)間：2018-05-16 19:11

  本文選題：人參皂甙Rd + 腦梗死��； 參考：《第四軍醫(yī)大學(xué)》2013年碩士論文

【摘要】：腦卒中具有發(fā)病率高、死亡率高和致殘率高的特點(diǎn)，嚴(yán)重威脅和影響著人類(lèi)的健康和人們的生活質(zhì)量。我國(guó)衛(wèi)生部在2008年公布的第三次全國(guó)居民死因調(diào)查結(jié)果中顯示：腦卒中已經(jīng)上升為我國(guó)居民死亡原因的第一位，其中缺血性腦卒中（腦梗死）約占全部腦卒中的80%以上，有效的治療是挽救患者生命、提高其生活質(zhì)量的關(guān)鍵，但受限于發(fā)病機(jī)制的復(fù)雜性，其治療一直是神經(jīng)病學(xué)的重難點(diǎn)所在。截至目前，腦卒中后的治療有多種方法，唯一有效的溶栓治療則受限于其過(guò)窄的治療時(shí)間窗和對(duì)出血等并發(fā)癥的顧忌，以及應(yīng)用時(shí)嚴(yán)格的適應(yīng)癥和眾多禁忌癥以及其他客觀(guān)原因，未能在臨床得到廣泛應(yīng)用；神經(jīng)保護(hù)治療方法經(jīng)過(guò)多年的研究和探索，也沒(méi)有在臨床試驗(yàn)中取得成功。這使得研究人員開(kāi)始在卒中的急性期和亞急性期內(nèi)尋求行之有效的神經(jīng)修復(fù)療法。而在腦缺血后，神經(jīng)功能缺損即使在不給予藥物治療的情況下，也能夠有一定程度的自我恢復(fù)，這可能與腦缺血后內(nèi)源性神經(jīng)發(fā)生的增加有關(guān)。因此，通過(guò)促進(jìn)內(nèi)源性神經(jīng)發(fā)生，，從而改善腦缺血后的神經(jīng)功能缺損癥狀，恢復(fù)神經(jīng)功能，成為當(dāng)前腦卒中后神經(jīng)修復(fù)治療的重要研究方向。 人參皂甙Rd（GSRd）是具有完全自主知識(shí)產(chǎn)權(quán)的國(guó)家一類(lèi)候選新藥。在以我院神經(jīng)內(nèi)科牽頭的多中心、隨機(jī)、雙盲、安慰劑對(duì)照的臨床試驗(yàn)結(jié)果中首次證實(shí)GSRd作為神經(jīng)保護(hù)劑的臨床有效性�；A(chǔ)研究方面，我們發(fā)現(xiàn)，腦梗死急性期（4小時(shí)）給予GSRd能夠減少大鼠梗死體積，促進(jìn)運(yùn)動(dòng)功能的恢復(fù)，作用機(jī)制可能與抑制氧化應(yīng)激損傷，維持線(xiàn)粒體膜電位有關(guān)。近期我們發(fā)現(xiàn)在腦梗死后的亞急性期（4-24小時(shí)）給予GSRd也能明顯促進(jìn)大鼠神經(jīng)功能恢復(fù)；同時(shí)，在動(dòng)物實(shí)驗(yàn)和細(xì)胞培養(yǎng)中發(fā)現(xiàn)：GSRd能夠促進(jìn)成年大鼠SVZ和SGZ的神經(jīng)干細(xì)胞/前體細(xì)胞的增殖、促進(jìn)體外培養(yǎng)的神經(jīng)干細(xì)胞向神經(jīng)元分化。鑒于此，我們推測(cè)：GSRd能明顯改善腦梗死亞急性期預(yù)后的機(jī)制可能與促進(jìn)神經(jīng)發(fā)生有關(guān)；如果能夠證實(shí)這個(gè)假設(shè)，將具有非常重要的臨床應(yīng)用價(jià)值，成為腦梗死后治療的突破性進(jìn)展。 目的：利用大鼠腦缺血/再灌注模型研究腦梗死后不同時(shí)間點(diǎn)給予GSRd對(duì)SVZ區(qū)神經(jīng)發(fā)生的影響。 方法：（1）成年SD雄性大鼠，線(xiàn)栓法建立短暫性局限性大鼠大腦中動(dòng)脈栓塞/再灌注（MCAO/R）模型，假手術(shù)組方法同模型組，但不阻斷MCA血供；通過(guò)神經(jīng)功能評(píng)分和TTC染色觀(guān)察動(dòng)物腦梗死模型的成功率和梗死體積的穩(wěn)定性。（2）MCAO/R和假手術(shù)大鼠在腦梗死后的6h、24h或3d腹腔注射GSRd（劑量為10mg/kg/d，共7d），對(duì)照組（模型組和假手術(shù)組）腹腔注射等體積GSRd專(zhuān)用溶劑；在用藥后即刻、1w、2w和3w灌注取材，進(jìn)行免疫組織化學(xué)染色，觀(guān)察SVZ區(qū)NSCs的增殖、遷移及分化情況，探討GSRd與神經(jīng)發(fā)生的關(guān)系。 結(jié)果：（1）線(xiàn)栓法建立大腦中動(dòng)脈栓塞/再灌注模型，梗死體積穩(wěn)定，成功率和長(zhǎng)期存活率較高。（2）在腦梗死后6h或24h給藥，與對(duì)照組比較，GSRd可顯著促進(jìn)NSCs增殖和遷移，且隨著時(shí)間延長(zhǎng)逐漸減弱，對(duì)分化的作用不明顯；腦梗死后第3d給予GSRd，對(duì)NSCs的增殖、遷移和分化情況與對(duì)照組之間無(wú)差異。 結(jié)論：在腦梗死后24h內(nèi)給予GSRd可促進(jìn)SVZ區(qū)的NSCs增殖，但不影響其遷移和分化。
[Abstract]:Stroke has the characteristics of high incidence, high mortality and high disability rate, which seriously threaten and affect human health and people's quality of life. The results of the third National Death survey published by the Ministry of health in 2008 showed that stroke has risen to be the first cause of death in our country, including ischemic stroke. (cerebral infarction) accounts for more than 80% of all stroke. Effective treatment is the key to save the life of the patient and improve the quality of life. But limited to the complexity of the pathogenesis, the treatment has been the most difficult problem in neurology. At present, there are many methods for the treatment after stroke, the only effective thrombolytic therapy is limited by its too narrow. The time window for the treatment and the scruples of complications such as bleeding, as well as the strict indications and many contraindications and other objective reasons in the application are not widely used in clinical practice; the neuroprotective therapy has not been successful in clinical trials after years of research and exploration. This makes the researchers start in the stroke. In the acute and subacute phase, an effective nerve repair therapy is sought. After cerebral ischemia, the neural function defect can also have a certain degree of self recovery, even in the absence of drug treatment, which may be related to the increase of endogenous neurogenesis after cerebral ischemia. Therefore, the endogenous neurogenesis can be improved by promoting endogenous neurogenesis. It is an important research direction of neural repair after stroke that good symptoms and neurological functions after cerebral ischemia.
Ginsenoside Rd (GSRd) is a national candidate drug with fully autonomous intellectual property rights. The clinical effectiveness of GSRd as a neuroprotective agent is first confirmed in the results of a multicenter, double-blind, placebo-controlled clinical trial, led by the neurology department of our hospital, and we have found that the acute phase of cerebral infarction (4 hours) is given to G. SRd can reduce the infarct volume and promote the recovery of motor function. The mechanism of action may be related to the inhibition of oxidative stress injury and the maintenance of mitochondrial membrane potential. In the near future, we found that the subacute phase (4-24 hours) after cerebral infarction (GSRd) can also significantly promote the recovery of neural function in rats; at the same time, in animal experiments and cell culture. Now: GSRd can promote the proliferation of neural stem cells / precursor cells of SVZ and SGZ in adult rats and promote the differentiation of neural stem cells from neurons in vitro. In view of this, we speculate that the mechanism of GSRd can obviously improve the mechanism of prognosis in the subacute phase of cerebral infarction and may be related to the promotion of neurogenesis. The important clinical application value has become a breakthrough in the treatment of cerebral infarction.
Objective: To study the effects of GSRd on the neurogenesis in the SVZ area at different time points after cerebral infarction in rats.
Methods: (1) Adult SD male rats were used to establish a transient localized rat model of middle cerebral artery embolism / reperfusion (MCAO/R), the sham operation group was the same as the model group, but did not block the MCA blood supply. The success rate and the stability of the infarct volume were observed by the neural function score and TTC staining. (2) MCAO/R and the sham operation. Rats were intraperitoneally injected with GSRd (10mg/kg/d, total 7D) in 6h, 24h or 3D after cerebral infarction. The control group (model group and sham operation group) was intraperitoneally injected with equal volume of GSRd specific solvent, and immediately after medication, 1W, 2W and 3W perfusion were obtained by immunohistochemistry. The proliferation, migration and differentiation of SVZ District NSCs were observed and the neurogenesis and neurogenesis were observed. The relationship.
Results: (1) the embolic and reperfusion model of middle cerebral artery was established by the method of thread embolism. The infarct volume was stable, the success rate and the long-term survival rate were higher. (2) 6h or 24h was given after cerebral infarction. Compared with the control group, GSRd could significantly promote the proliferation and migration of NSCs, and the effect on differentiation was not obvious with the time prolonged; 3D was given to GSR after cerebral infarction. D, there was no difference in the proliferation, migration and differentiation of NSCs between the control group and the control group.
Conclusion: GSRd in 24h after cerebral infarction can promote the proliferation of NSCs in SVZ region, but it does not affect its migration and differentiation.
【學(xué)位授予單位】：第四軍醫(yī)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2013
【分類(lèi)號(hào)】：R743.33

【參考文獻(xiàn)】

相關(guān)期刊論文 前6條

1 徐彥立;王景超;張思森;;亞低溫對(duì)腦梗死IL-6和sICAM-1表達(dá)的影響[J];中國(guó)實(shí)用神經(jīng)疾病雜志;2010年03期

2 朱文斌;徐運(yùn);;急性腦梗死的動(dòng)脈溶栓治療[J];國(guó)際腦血管病雜志;2007年10期

3 石潔;趙鋼;夏峰;饒志仁;劉娟芳;徐曉菲;葉瑞東;;不同濃度人參皂甙Rd對(duì)次聲性腦損害的保護(hù)[J];中華神經(jīng)外科疾病研究雜志;2008年05期

4 張均田;人參皂苷Rg1的促智作用機(jī)制——對(duì)神經(jīng)可塑性和神經(jīng)發(fā)生的影響[J];藥學(xué)學(xué)報(bào);2005年05期

5 胡文立;;2009急性缺血性腦卒中臨床研究回顧[J];中國(guó)醫(yī)藥導(dǎo)報(bào);2010年10期

6 魏居瑞;劉U

本文編號(hào)：1898072