【摘要】：研究背景不穩(wěn)定型心絞痛(Unstable angina,UA)的發(fā)病的機(jī)制是在動(dòng)脈粥樣硬化的基礎(chǔ)上冠脈內(nèi)不穩(wěn)定的粥樣斑塊繼發(fā)病理改變,使局部心肌血流量明顯下降,如斑塊內(nèi)出血、斑塊纖維帽出血裂隙、表面上有血小板聚集及(或)刺激冠狀動(dòng)脈痙攣,導(dǎo)致缺血加重。不穩(wěn)定型心絞痛是冠心病的常見類型之一,既往大量研究表明慢性免疫炎癥反應(yīng)貫穿于在動(dòng)脈粥樣硬化的過(guò)程,炎癥遞質(zhì)激活效應(yīng)細(xì)胞產(chǎn)生炎性因子,進(jìn)而可影響斑塊纖維帽的穩(wěn)定性促使動(dòng)脈粥樣硬化斑塊內(nèi)出現(xiàn)破裂、出血,最后導(dǎo)致不穩(wěn)定斑塊的形成。B7-H3和B7-H4是近些年來(lái)研究較熱的B7共刺激分子家族新成員。最新研究證實(shí)人和鼠的B7-H3、B7-H4都能有效抑制CD4+T淋巴細(xì)胞激活和炎性因子如干擾素-γ(Interferon-γ,IFN-γ)、白細(xì)胞介素-4(Interleukin-4,IL-4)的產(chǎn)生的作用,并可負(fù)性調(diào)節(jié)T淋巴細(xì)胞活化。張小民團(tuán)隊(duì)等人關(guān)于B7-H3的探索發(fā)現(xiàn)頸動(dòng)脈硬化患者血清可溶性B7-H3(s B7-H3)分泌水平較健康對(duì)照組明顯升高。既往對(duì)這兩個(gè)指標(biāo)的研究主要局限于腫瘤性疾病,關(guān)于B7-H3、B7-H4與動(dòng)脈粥樣硬化(atherosclerosis,AS)之間的關(guān)系的研究罕見報(bào)道。目的探討強(qiáng)化劑量阿托伐他汀對(duì)不穩(wěn)定型心絞痛患者經(jīng)皮冠狀動(dòng)脈介入術(shù)(Percutaneous coronary intervention,PCI)圍手術(shù)期B7-H3及B7-H4的表達(dá)的影響。方法將80例不穩(wěn)定型心絞痛患者按隨機(jī)數(shù)字表法分為強(qiáng)化劑量阿托伐他汀組(n=40)和常規(guī)劑量阿托伐他汀組(n=40),強(qiáng)化劑量組于PCI術(shù)前48h口服阿托伐他汀80mg/d治療,術(shù)后給阿托伐他汀40 mg/d;常規(guī)劑量組于PCI術(shù)前48h、術(shù)后口服阿托伐他汀20mg/d治療。分別于PCI術(shù)前、術(shù)后18-24h收集患者外周靜脈血,酶聯(lián)免疫吸附試驗(yàn)(Enzyme-linked immuno sorbent assay,ELISA)檢測(cè)血清IL-4、IL-10、IFN-γ、s B7-H3、s B7-H4濃度水平,用實(shí)時(shí)熒光定量PCR反應(yīng)(Realtime fluorescent quantitative Reverse transcription-polymerase chain reaction,q RT-PCR)檢測(cè)外周血單核細(xì)胞(Peripheral blood mononuclear cell,PBMC)B7-H3m RNA和B7-H4m RNA相對(duì)表達(dá)量。結(jié)果(1)PCI術(shù)前,兩組患者血清IL-4、IL-10、IFN-γ濃度水平無(wú)統(tǒng)計(jì)學(xué)差異(P0.05);PCI術(shù)后,常規(guī)劑量組和強(qiáng)化劑量組患者血清IL-4、IFN-γ濃度水平較術(shù)前降低,其中強(qiáng)化劑量組下降更明顯,差異有統(tǒng)計(jì)學(xué)差異(P0.05);相反,血清IL-10濃度水平較術(shù)前上升,而且強(qiáng)化劑量組血清IL-10水平升高更顯著,差異有統(tǒng)計(jì)學(xué)差異(P0.05);(2)PCI術(shù)前,兩組患者s B7-H3、s B7-H4濃度水平無(wú)明顯差異(P0.05);PCI術(shù)后,兩組患者s B7-H3、s B7-H4濃度水平均上升,其中強(qiáng)化劑量組s B7-H3、s B7-H4水平升高更顯著,差異有統(tǒng)計(jì)學(xué)意義(P0.05);(3)PCI術(shù)前,兩組患者B7-H3m RNA、B7-H4m RNA表達(dá)水平無(wú)顯著差異(P0.05);PCI術(shù)后,常規(guī)劑量組PCI術(shù)后B7-H3、B7-H4m RNA表達(dá)水平較術(shù)前無(wú)明顯變化,差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05);強(qiáng)化劑量組B7-H3、B7-H4m RNA表達(dá)較術(shù)前明顯升高,差異有統(tǒng)計(jì)學(xué)意義(P0.05);(4)線性相關(guān)分析顯示:B7-H3 m RNA與IL-10呈正性相關(guān),相關(guān)系數(shù)r=0.629,(P0.05),與IL-4、IFN-γ水平分別呈負(fù)性相關(guān)(r=-0.342,r=-0.417,均P0.05);B7-H4m RNA與IL-10呈正性相關(guān)(r=0.599,P0.05),與IL-4、IFN-γ分別呈負(fù)性相關(guān)(r=-0.391,r=-0.458,均P0.05)。結(jié)論強(qiáng)化劑量阿托伐他汀可能通過(guò)促進(jìn)B7-H3、B7-H4表達(dá),從而降低不穩(wěn)定型心絞痛患者PCI圍手術(shù)期免疫炎癥反應(yīng)。
[Abstract]:The mechanism of the study on the pathogenesis of unstable angina (UA) is the secondary pathological change of the unstable atherosclerotic plaque on the basis of the atherosclerosis, so that the local myocardial blood flow is obviously reduced, such as the plaque hemorrhage, the plaque fiber cap hemorrhage fracture, Platelet aggregation and/ or stimulation of coronary artery spasm on the surface leads to an increase in ischemia. unstable angina is one of the most common types of coronary heart disease, and a large number of previous studies have shown that the chronic immune inflammatory response runs through the process of atherosclerosis, the inflammatory and active effect cells producing an inflammatory factor, further, the stability of the plaque fiber cap can be affected to cause a rupture and a hemorrhage in the atherosclerotic plaque, and finally, the formation of the unstable plaque can be caused. B7-H3 and B7-H4 are new members of the B7 costimulatory molecule family that have been studied in recent years. The most recent studies confirm that both B7-H3 and B7-H4 of human and mouse can effectively inhibit the activation of CD4 + T lymphocytes and the effect of inflammatory factors such as Interferon-1 (IFN-1), interleukin-4 (Interleukin-4, IL-4), and can negatively regulate the activation of T-lymphocytes. The results showed that the level of serum soluble B7-H3 (s 7-H3) in the patients with carotid arteriosclerosis was significantly higher than that in the healthy control group. Previous studies of these two indicators are mainly limited to the neoplastic disease, and the study of the relationship between B7-H3, B7-H4 and atherosclerosis (AS) is rare. Objective To investigate the effect of intensive dose of atorvastatin on the expression of B7-H3 and B7-H4 in patients with unstable angina undergoing percutaneous coronary intervention (PCI). Methods 80 patients with unstable angina were divided into intensive dose of atorvastatin (n = 40) and conventional dose of atorvastatin (n = 40). The conventional dose group was treated with atorvastatin 20mg/ d before and after PCI. Serum IL-4, IL-10, IFN-1, s B7-H3, s B7-H4 concentration levels were detected by enzyme-linked immunosorbent assay (ELISA) before and after PCI, and the real-time fluorescence quantitative PCR reaction was used. The relative expression of B7-H3m and B7-H4m in peripheral blood mononuclear cells (PBMC) was detected by q-RT-PCR. Results (1) Before PCI, the levels of IL-4, IL-10 and IFN-2 in serum of the two groups were not significantly different (P0.05). The levels of IL-4 and IFN-1 in the patients with conventional and intensive dose groups were lower than that before PCI. There was a significant difference in serum IL-10 concentration in the two groups (P0.05). In contrast, the level of serum IL-10 increased significantly, and the level of serum IL-10 in the intensive dose group was higher and the difference was statistically different (P0.05); (2) Before PCI, there was no significant difference between the two groups of patients's B7-H3, s B7-H4 (P0.05); after PCI, The levels of sB7-H3 and sB7-H4 in the two groups increased, and the level of B7-H3, s B7-H4 was higher in the two groups, and the difference was significant (P0.05). (3) The expression of B7-H3m RNA and B7-H4m in the two groups was not significantly different (P0.05). There was no significant difference in the expression of B7-H4m (P0.05). The expression of B7-H3 and B7-H4m in the intensive dose group was significantly higher than that before operation (P0.05). (4) The linear correlation analysis showed that the B7-H3 mRNA was positively related to IL-10, and the correlation coefficient was r = 0.629. (P <0.05), and negative correlation with IL-4 and IFN-1 levels (r =-0.342, r =-0.417, all P0.05); the positive correlation between B7-H4m and IL-10 (r =-0.599, P0.05), and negative correlation with IL-4 and IFN-2 (r =-0.391, r =-0.458, all P0.05). Conclusion The enhanced dose of atorvastatin may be expressed by promoting the expression of B7-H3, B7-H4, thereby reducing the immune inflammatory response of PCI in patients with unstable angina.
【學(xué)位授予單位】：廣西醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R541.4

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