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强化剂量阿托伐他汀对不稳定型心绞痛患者PCI围手术期B7-H3及B7-H4的影响

发布时间:2019-02-11 21:09  文章来源:笔耕文化传播
【摘要】:研究背景不稳定型心绞痛(Unstable angina,UA)的发病的机制是在动脉粥样硬化的基础上冠脉内不稳定的粥样斑块继发病理改变,使局部心肌血流量明显下降,如斑块内出血、斑块纤维帽出血裂隙、表面上有血小板聚集及(或)刺激冠状动脉痉挛,导致缺血加重。不稳定型心绞痛是冠心病的常见类型之一,既往大量研究表明慢性免疫炎症反应贯穿于在动脉粥样硬化的过程,炎症递质激活效应细胞产生炎性因子,进而可影响斑块纤维帽的稳定性促使动脉粥样硬化斑块内出现破裂、出血,最后导致不稳定斑块的形成。B7-H3和B7-H4是近些年来研究较热的B7共刺激分子家族新成员。最新研究证实人和鼠的B7-H3、B7-H4都能有效抑制CD4+T淋巴细胞激活和炎性因子如干扰素-γ(Interferon-γ,IFN-γ)、白细胞介素-4(Interleukin-4,IL-4)的产生的作用,并可负性调节T淋巴细胞活化。张小民团队等人关于B7-H3的探索发现颈动脉硬化患者血清可溶性B7-H3(s B7-H3)分泌水平较健康对照组明显升高。既往对这两个指标的研究主要局限于肿瘤性疾病,关于B7-H3、B7-H4与动脉粥样硬化(atherosclerosis,AS)之间的关系的研究罕见报道。目的探讨强化剂量阿托伐他汀对不稳定型心绞痛患者经皮冠状动脉介入术(Percutaneous coronary intervention,PCI)围手术期B7-H3及B7-H4的表达的影响。方法将80例不稳定型心绞痛患者按随机数字表法分为强化剂量阿托伐他汀组(n=40)和常规剂量阿托伐他汀组(n=40),强化剂量组于PCI术前48h口服阿托伐他汀80mg/d治疗,术后给阿托伐他汀40 mg/d;常规剂量组于PCI术前48h、术后口服阿托伐他汀20mg/d治疗。分别于PCI术前、术后18-24h收集患者外周静脉血,酶联免疫吸附试验(Enzyme-linked immuno sorbent assay,ELISA)检测血清IL-4、IL-10、IFN-γ、s B7-H3、s B7-H4浓度水平,用实时荧光定量PCR反应(Realtime fluorescent quantitative Reverse transcription-polymerase chain reaction,q RT-PCR)检测外周血单核细胞(Peripheral blood mononuclear cell,PBMC)B7-H3m RNA和B7-H4m RNA相对表达量。结果(1)PCI术前,两组患者血清IL-4、IL-10、IFN-γ浓度水平无统计学差异(P0.05);PCI术后,常规剂量组和强化剂量组患者血清IL-4、IFN-γ浓度水平较术前降低,其中强化剂量组下降更明显,差异有统计学差异(P0.05);相反,血清IL-10浓度水平较术前上升,而且强化剂量组血清IL-10水平升高更显著,差异有统计学差异(P0.05);(2)PCI术前,两组患者s B7-H3、s B7-H4浓度水平无明显差异(P0.05);PCI术后,两组患者s B7-H3、s B7-H4浓度水平均上升,其中强化剂量组s B7-H3、s B7-H4水平升高更显著,差异有统计学意义(P0.05);(3)PCI术前,两组患者B7-H3m RNA、B7-H4m RNA表达水平无显著差异(P0.05);PCI术后,常规剂量组PCI术后B7-H3、B7-H4m RNA表达水平较术前无明显变化,差异无统计学意义(P0.05);强化剂量组B7-H3、B7-H4m RNA表达较术前明显升高,差异有统计学意义(P0.05);(4)线性相关分析显示:B7-H3 m RNA与IL-10呈正性相关,相关系数r=0.629,(P0.05),与IL-4、IFN-γ水平分别呈负性相关(r=-0.342,r=-0.417,均P0.05);B7-H4m RNA与IL-10呈正性相关(r=0.599,P0.05),与IL-4、IFN-γ分别呈负性相关(r=-0.391,r=-0.458,均P0.05)。结论强化剂量阿托伐他汀可能通过促进B7-H3、B7-H4表达,从而降低不稳定型心绞痛患者PCI围手术期免疫炎症反应。
[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.
【学位授予单位】:广西医科大学
【学位级别】:硕士
【学位授予年份】:2017
【分类号】:R541.4

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