【摘要】：目的腦梗死是嚴(yán)重危害人類身體健康和生命的主要疾病之一。發(fā)病后4.5h內(nèi)靜脈給予rt-PA的溶栓治療是目前公認(rèn)最有效的治療方法。然而,溶栓治療是一把雙刃劍,出血轉(zhuǎn)化(HT)為腦梗死溶栓后最嚴(yán)重的并發(fā)癥。溶栓后出血轉(zhuǎn)化發(fā)生的相關(guān)機(jī)制目前仍不明確,其中血腦屏障(BBB)損害學(xué)說被認(rèn)為意義重大。研究表明,小窩蛋白-1(caveolin-1)、金屬基質(zhì)蛋白酶-9(MMP-9)之間相互作用,與血腦屏障完整性的破壞有關(guān)。臨床試驗(yàn)中將caveolin-1、MMP-9作為生物學(xué)標(biāo)志物,探索其與腦梗死患者靜脈溶栓預(yù)后相關(guān)性的研究很少見。本課題擬通過檢測(cè)腦梗死溶栓患者血漿caveolin-1、MMP-9的水平,探討其與溶栓后出血轉(zhuǎn)化的關(guān)系,對(duì)溶栓后出血轉(zhuǎn)化的發(fā)生進(jìn)行早期預(yù)判,減少溶栓后出血轉(zhuǎn)化發(fā)生的風(fēng)險(xiǎn)。方法本實(shí)驗(yàn)共納入40例患者,其中出血轉(zhuǎn)化組3例,對(duì)照組37例。于患者入院溶栓前進(jìn)行血液標(biāo)本的采集及相關(guān)基本臨床資料的收集。caveolin-1、MMP-9水平通過酶聯(lián)免疫吸附試驗(yàn)(ELISA)方法進(jìn)行檢測(cè)。兩組數(shù)據(jù)間比較及基線臨床資料的統(tǒng)計(jì)分析應(yīng)用統(tǒng)計(jì)學(xué)軟件spss18.0進(jìn)行分析。結(jié)果1腦梗死溶栓后出血轉(zhuǎn)化組患者血漿caveolin-1、MMP-9的含量明顯高于對(duì)照組(P㩳0.01)。2.預(yù)后不佳組患者(m RS=3~6分)血漿中caveolin-1表達(dá)水平較對(duì)照組增加(P㩳0.05)。3.所有入組腦梗死溶栓患者血漿caveolin-1、MMP-9的表達(dá)呈顯著正相關(guān)(r=0.462,P㩳0.01)。4.患者年齡、血糖水平、caveolin-1、MMP-9水平是溶栓后出血轉(zhuǎn)化發(fā)生可能的危險(xiǎn)因素,通過多因素分析提示caveolin-1、MMP-9水平可能可以預(yù)測(cè)溶栓后出血轉(zhuǎn)化的發(fā)生(P㩳0.05)。5.年齡、吸煙史、房顫、溶栓前NIHSS評(píng)分、血漿caveolin-1的表達(dá)可能是影響溶栓患者的預(yù)后的危險(xiǎn)因素(P㩳0.05)。結(jié)論caveolin-1、MMP-9在溶栓后發(fā)生出血轉(zhuǎn)化的患者血漿中表達(dá)增高。caveolin-1為影響溶栓后出血轉(zhuǎn)化的發(fā)生及預(yù)后的重要危險(xiǎn)因素。此結(jié)果支持caveolin-1、MMP-9可能成為預(yù)測(cè)腦梗死溶栓患者發(fā)生出血轉(zhuǎn)化的有效指標(biāo),并可能成為治療溶栓后出血轉(zhuǎn)化的一個(gè)新的靶點(diǎn)。
[Abstract]:Objective Cerebral infarction is one of the major diseases that seriously endanger human health and life. Thrombolytic therapy by intravenous administration of rt-PA within 4.5 hours after onset of disease is recognized as the most effective treatment. However, thrombolytic therapy is a double-edged sword. Bleeding translates into (HT) as the most serious complication after thrombolysis in cerebral infarction. The mechanism of hemorrhage and transformation after thrombolysis is still unclear, among which the theory of blood-brain barrier (BBB) damage is considered to be of great significance. The interaction between fossa protein 1 (caveolin-1) and metalloproteinase-9 (MMP-9) is related to the damage of blood-brain barrier integrity. In clinical trials, caveolin-1 MMP-9 is used as a biomarker, and it is rare to explore its correlation with the prognosis of venous thrombolytic therapy in patients with cerebral infarction. The aim of this study was to detect the level of plasma caveolin-1 MMP-9 in patients with cerebral infarction, and to explore the relationship between the level of MMP-9 and bleeding transformation after thrombolytic therapy, to predict the occurrence of hemorrhage transformation after thrombolytic therapy and to reduce the risk of hemorrhage transformation after thrombolytic therapy. Methods A total of 40 patients were included in the study, including 3 cases in the bleeding conversion group and 37 cases in the control group. The blood samples were collected before thrombolytic therapy and the basic clinical data were collected. The level of MMP-9 was detected by enzyme linked immunosorbent assay (ELISA). The comparison between the two groups of data and the statistical analysis of baseline clinical data were analyzed by statistical software spss18.0. Results (1) the level of plasma caveolin-1 MMP-9 in patients with hemorrhage transformation after thrombolysis after cerebral infarction was significantly higher than that in control group (P0. 01). The expression of caveolin-1 in the patients with poor prognosis (mRSv 3 ~ 6) was higher than that in the control group (P0. 05). There was a significant positive correlation between the expression of plasma caveolin-1 and MMP-9 in all patients with thrombolytic therapy of cerebral infarction (r = 0.462P ~ (0.01) .4. Age, blood glucose level and MMP-9 level were the possible risk factors of hemorrhage transformation after thrombolytic therapy. It was suggested that the level of caveolin-1 MMP-9 might predict the occurrence of hemorrhage transformation after thrombolysis (P0. 05). Age, smoking history, atrial fibrillation, pre-thrombolytic NIHSS score and plasma caveolin-1 expression may be risk factors for prognosis of thrombolytic patients (P0. 05). Conclusion the increased expression of caveolin-1 MMP-9 in plasma of patients with hemorrhage and transformation after thrombolytic therapy is an important risk factor for the occurrence and prognosis of bleeding transformation after thrombolytic therapy. These results suggest that caveolin-1 MMP-9 may be an effective marker for predicting hemorrhage transformation in patients with cerebral infarction and may be a new target for the treatment of bleeding transformation after thrombolysis.
【學(xué)位授予單位】：西安醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R743.3

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