12-脂加氧酶及其抑制剂黄芩素在实验性小鼠病毒性心肌炎中的作用

发布时间：2018-03-09 00:22

本文选题：12-脂加氧酶　切入点：病毒性心肌炎　出处：《吉林大学》2012年博士论文　论文类型：学位论文

【摘要】：病毒性心肌炎（viral myocarditis，VMC）是儿科临床常见的心血管疾病，近年发病有上升趋势，并且已成为青少年不明原因猝死的主要原因之一，不仅如此，慢性VMC还可导致扩张性心肌病的发生，严重危害小儿生命健康。因VMC发病机制尚未完全阐明，至今国内外对VMC尚无特效的治疗方法。 12-脂加氧酶(12-LO)是一类以非血红素铁蛋白为辅基的多功能酶，属于脂质酶家族中的一种，广泛分布于机体各部分，具有多种生物功能；12-LO又是一种重要的信号分子，能够促进细胞的增殖，通过机体氧化应激反应和炎症反应，参与多种疾病病理过程，并在心血管方面具有重要作用，参与了高血压、动脉粥样硬化等疾病的病理过程。但目前国内外对12-LO与病毒性心肌炎的关系尚无研究。本研究通过采用BALB/C小鼠腹腔注射柯萨奇B3病毒（CVB3）的经典制作病毒性心肌炎模型的方法，建立病毒性心肌炎小鼠模型。通过半定量RT-PCR方法、免疫组织化学方法确定了12-LO在VMC发病过程中的作用，证实了12-LO与VMC发病过程中心肌病理积分、肌酸激酶同工酶质量(CK-MB mass)等指标呈正相关，并与细胞内游离钙（Ca2+）、一氧化氮(NO)进行相关分析，发现12-LO可能是NO和细胞内Ca2+的促发因子。并应用12-LO抑制剂黄芩素对病毒性心肌炎小鼠进行干预，有效的降低了VMC小鼠心肌中12-LO的表达，减轻VMC病情，表明12-LO抑制剂黄芩素对小鼠病毒性心肌炎具有一定的治疗效果。结果说明12-LO在小鼠病毒性心肌炎发病过程中有重要作用，通过降低CVB3感染后小鼠心肌组织12-LO的表达可减轻VMC病情，，为病毒性心肌炎的临床治疗应用提供了理论和实验依据。本研究创新点:探讨12－LO在VMC中的作用，并观察12－LO抑制剂黄芩素对VMC小鼠动物模型的干预作用。
[Abstract]:Viral myocarditis (VMC) is a common cardiovascular disease in pediatric clinic. In recent years, the incidence of viral myocarditis is on the rise, and it has become one of the main causes of sudden death in adolescents. Not only that, chronic VMC can also lead to the occurrence of dilated cardiomyopathy. The pathogenesis of VMC has not been fully elucidated and there is no effective treatment for VMC at home and abroad. 12- lipoxygenase (12-LOA) is a kind of multifunctional enzyme with non-heme ferritin as the cogroup, which belongs to the lipase family and is widely distributed in various parts of the body. 12-LO is a kind of important signal molecule with various biological functions. It can promote cell proliferation, participate in many pathological processes through oxidative stress and inflammation, play an important role in cardiovascular, and participate in hypertension. However, the relationship between 12-LO and viral myocarditis has not been studied at home and abroad. The method of making viral myocarditis model by intraperitoneal injection of coxsackie B3 virus CVB3 into BALB/C mice was used in this study. The role of 12-LO in the pathogenesis of VMC was determined by semi-quantitative RT-PCR method and immunohistochemical method, and the pathological integrals of 12-LO and VMC in the pathogenesis of VMC were confirmed. Creatine kinase isoenzyme (CK-MB) was positively correlated with intracellular free Ca ~ (2 +) (Ca ~ (2 +)) and nitric oxide (no). It was found that 12-LO may be the stimulating factor of no and intracellular Ca2, and the intervention of baicalin, a 12-LO inhibitor, on viral myocarditis mice could effectively reduce the expression of 12-LO in the myocardium of VMC mice and alleviate the condition of VMC. The results showed that the 12-LO inhibitor baicalin had a certain therapeutic effect on viral myocarditis in mice. The results showed that 12-LO had an important role in the pathogenesis of viral myocarditis in mice. By reducing the expression of 12-LO in the myocardium of mice infected with CVB3, the condition of VMC can be alleviated, which provides theoretical and experimental basis for the clinical treatment of viral myocarditis. The purpose of this study was to investigate the role of 12-LO in VMC and to observe the effects of baicalin, a 12-LO inhibitor, on VMC mice.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2012
【分类号】：R285.5;R725.4

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