红花黄色素对2型糖尿病合并动脉粥样硬化者氧化应激及炎症反应的影响

发布时间：2018-05-26 05:01

本文选题：2型糖尿病 + 动脉粥样硬化　；参考：《山东大学》2017年硕士论文

【摘要】：研究背景近年来,随着经济的发展以及现代生活方式的改变,2型糖尿病、肥胖等代谢性疾病的患病率呈快速上升趋势,给人类健康带来极大威胁。T2DM可引起全身各个系统和重要器官的病变,导致心血管事件、脑卒中、终末期肾脏疾病、失明等严重并发症,致残及致死率高,其中心血管并发症是其的最主要死因。T2DM发病率的增长与全球性肥胖的流行直接相关,腹型肥胖作为代谢综合征临床表现的组成部分,代谢紊乱是其突出临床特点,增加了患者发展为T2DM和动脉粥样硬化性大血管病的风险。随着肥胖发病率的日益增加,肥胖T2DM患者比例也迅速升高,其动脉粥样硬化的发生率也迅速上升。T2DM及肥胖这两个心脑血管事件的独立危险因素合并存在,极大地增加了机体代谢紊乱的复杂性,提高了 T2DM患者大血管病变的发生率,同时也加重了病情严重程度和不良预后,给T2DM的临床诊治工作带来严峻挑战。因此充分认识肥胖T2DM合并大血管病变患者的临床特点,才能在当前诊疗经验基础上更有的放矢的进行治疗,延缓病情进展。如何更能有效的治疗并改善T2DM合并AS及肥胖患者预后,降低死亡率是当前临床治疗及研究的热点及难点。现阶段T2DM的临床常规治疗主要为降糖、调脂、抗凝、降压、改善循环等。T2DM时的慢性高血糖状态已被证实主要是通过氧化应激、炎症反应和胰岛素抵抗来影响机体功能,因此在上述常规治疗手段外,针对这些可能的病理生理改变的治疗方法也逐渐在临床上应用,并证实有效。近些年的大量研究发现上述病理生理改变可能为T2DM、肥胖和AS的共同发病机制,因此相关抗炎、抗氧化治疗有望在肥胖T2DM合并AS患者治疗中取得较好疗效。研究目的本研究主要目的是探讨肥胖和正常体重T2DM合并AS者氧化应激及炎症反应状态的变化特点,并探讨红花黄色素治疗对T2DM合并AS者氧化应激及炎症反应有关指标的影响,进而评价红花黄色素抗氧化应激及炎症反应的临床应用价值。研究方法研究对象:通过以下入排标准招募研究对象,进而尽可能控制影响氧化应激和炎症反应水平的其他混杂因素。选择2015.10.01-2016.07.01于齐鲁医院门诊就诊及住院的T2DM合并AS患者117例(男58例,女59例),临床资料均完备。根据BMI将患者分为正常体重组(BMI24)(A组,60例)和肥胖组(BMI≥28)(B组,57例),其中A组男性31人,女性29人,平均年龄,60.41±5.65岁。B组男性27人,女性30人,平均年龄59.11 ±4.81岁。纳入标准:①确诊为T2DM,诊断标准参照1999年WHO制定的糖尿病诊断标准;②颈动脉或下肢动脉超声检查发现动脉粥样硬化性斑块者;③年龄45-76周岁者,性别不限;④糖化血红蛋白GHbAlc7%,血糖控制达标者,以排除血糖水平对氧化应激及炎症水平的影响;⑤血压140/90mmHg,以排除血压水平对氧化应激及炎症水平的影响;⑥患者及其家属知情同意。排除标准:①有脑卒中、心肌梗死及其他大血管栓塞病史者;②重大外伤手术史、移植史、肿瘤、烧伤等应激状态者;③伴有严重的肝肾脏疾病者,如急、慢性肝、肾功能不全或衰竭等;④有急、慢性感染疾病证据;⑤有免疫疾病,如慢性结缔组织病、AIDS等;⑥近期服用抗炎或是免疫抑制药物;⑦有药物或酒精依赖史或精神疾病史。资料收集:①收集所有患者的一般临床情况,主要包括年龄、性别、体重、身高、腹围、烟酒史、常见慢性病史、传染病史、手术及外伤史、家族史、女性询问月经及婚育史,并计算体重质量指数BMI(Kg/m2)=体重(Kg)/身高2(m2)。②患者给予一般常规的降糖、降压、调脂等治疗后,给予红花黄色素注射液治疗14d,并分别于治疗前后,检测受试者空腹血清血脂、ox-LDL、8-iso-PGF2α、sICAM-1、IL-6、TNF-α、GPxl 和 IL-10 水平。统计方法:本研究中所有数据的统计分析及处理采用Excel 2007及SPSS 19.0软件。计量资料符合正态分布者以均数±标准差(x±s)表示,组间数据比较用独立样本t检验分析;非正态分布者采取自然对数转换为符合正态分布要求;干预治疗前后数据分析采用配对t检验分析;结果中p0.05有统计学意义。研究结果1.红花黄色素治疗前,A组和B组一般情况基线水平比较,结果提示血清TG、HDL-C、ox-LDL、8-iso-PGF2α、sICAM-1、IL-6 和 TNF-α 水平在两组之间有统计学差异。2.红花黄色素治疗14d后,对A组患者治疗前后相关代谢指标及生物标志物进行比较,比较结果显示治疗后血清ox-LDL、8-iso-PGF2α、sICAM-1、TNF-α、IL-6、IL-10和GPxl的水平变化具有统计学意义。3.红花黄色素治疗14d后,对B组患者治疗前后相关代谢指标及生物标志物进行比较,比较结果显示治疗后血清ox-LDL、8-iso-PGF2α、sICAM-1、TNF-α、IL-6、IL-10和GPxl的水平变化有统计学差异。4.红花黄色素治疗14d后,对A组和B组患者在治疗前后相关代谢指标及生物标志物的差值进行组间比较,结果显示在治疗后B组血清sICAM-1、TNF-α、IL-6和8-iso-PGF2 α水平降低更显著,差异具有统计学意义。研究结论1.相较于正常体重T2DM合并AS者,肥胖T2DM合并AS者的氧化应激状态及炎症反应更明显。2.红花黄色素注射液可降低肥胖及正常体重T2DM合并AS者的氧化应激状态及炎症反应水平,并可能在肥胖T2DM合并AS者中的作用更为显著。3.应用红花黄色素可以抑制氧化应激和炎症反应,可能有利于防治AS并延缓AS的进展,进而有利于减少心脑血管事件的发生率。红花黄注射液有可能成为临床肥胖T2DM合并AS者防治氧化应激及炎症反应的有效药物。
[Abstract]:In recent years, with the development of economy and the change of modern lifestyle, the prevalence of metabolic diseases such as type 2 diabetes, obesity and other metabolic diseases is on the rise rapidly, causing a great threat to human health, which can cause diseases of all systems and important organs of the whole body, leading to cardiovascular events, stroke, end-stage renal disease, blindness. Severe complications, disability and death rate are high, in which cardiovascular complications are the main causes of the death of the.T2DM and the prevalence of global obesity is directly related. Abdominal obesity is a part of the clinical manifestation of metabolic syndrome. Metabolic disorders are its prominent clinical features, increasing the development of patients with T2DM and atherosclerosis. The risk of sexual great vascular disease. With the increasing incidence of obesity, the proportion of obese T2DM patients has also increased rapidly. The incidence of atherosclerosis is also rapidly rising in the incidence of.T2DM and obesity, the two independent risk factors of cardiovascular events, which greatly increase the complexity of the body metabolic disorder and increase the large blood of T2DM patients. The incidence of tube lesions, which also aggravates the severity and poor prognosis of the disease, brings severe challenges to the clinical diagnosis and treatment of T2DM. Therefore, it is more effective to understand the clinical characteristics of the patients with obesity T2DM combined with large vascular diseases so as to have more sagittal treatment on the basis of the current experience of diagnosis and treatment and delay the progress of the disease. The treatment and improvement of the prognosis of T2DM combined with AS and obese patients is a hot and difficult point in current clinical treatment and research. At present, the main clinical treatment of T2DM is hypoglycemic, lipid regulating, anticoagulant, hypotension, and improving circulation and other.T2DM, which have been proved to be mainly through oxidative stress, inflammatory reaction and insulin. In recent years, a large number of studies have found that the pathophysiological changes may be the common pathogenesis of T2DM, obesity and AS, so the related anti-inflammatory and antioxidant therapy has been found. The main purpose of this study is to explore the changes in oxidative stress and inflammatory response in obese and normal weight T2DM combined with AS, and to explore the effects of red flower yellow on oxidative stress and inflammatory response in T2DM combined with AS, and to evaluate the effect of red flower yellow on the oxidative stress and inflammatory response in T2DM combined with AS. The clinical application value of the antioxidant stress and inflammatory response of the yellow pigment. Research object: to recruit research subjects through the following criteria, and to control other confounding factors affecting the level of oxidative stress and inflammatory response as far as possible. Select 2015.10.01-2016.07.01 in the T2DM patients with AS in Qilu Hospital and the hospitalized patients in Qilu Hospital, 1 17 cases (male 58, female 59 cases) were all complete. According to BMI, the patients were divided into normal weight group (BMI24) (group A, 60 cases) and obesity group (BMI > 28) (group B, 57 cases). Among them, there were 31 men in group A, 29 women, average age, 60.41 + 5.65 years old.B group, 27, 30, average age 59.11 + 5 years. Reference to the diabetes diagnostic criteria established by WHO in 1999; (2) the atherosclerotic plaque in the carotid or lower extremities was detected by ultrasonography; (3) the age 45-76 years old, sex unlimited; (4) glycated hemoglobin GHbAlc7%, the blood sugar control to the standard, to exclude the effect of blood glucose level on the oxygen stress and the level of inflammation; (5) blood pressure 140/90mmHg, Exclude the effects of blood pressure on oxidative stress and inflammatory levels; 6. Patients and their families informed consent. Exclusion criteria: (1) patients with stroke, myocardial infarction and other major vascular embolism history; (2) major trauma surgery history, transplant history, tumor, burn and other stress states; (3) patients with serious liver and kidney diseases, such as acute, chronic liver, and renal function Incomplete or exhaustion; (4) evidence of acute and chronic infection; (5) immune diseases, such as chronic connective tissue disease, AIDS, etc.; (6) taking anti inflammatory or immunosuppressive drugs in the near future; (7) the history of drug or alcohol dependence or mental illness. Data collection: (1) collection of general clinical conditions in all patients, including age, sex, weight, height, and height, Abdominal circumference, the history of chronic disease, the history of infectious diseases, the history of operation and trauma, family history, women's history of menstruation and marriage, and the weight mass index BMI (Kg/m2) = weight (Kg) / height 2 (M2). 2. Patients given general routine hypoglycemic, depressurization, and lipid regulation were treated with safflower yellow injection for treatment of 14d, and before and after treatment, respectively. Serum lipid, ox-LDL, 8-iso-PGF2 alpha, sICAM-1, IL-6, TNF- alpha, GPxl and IL-10 levels were detected in the subjects. Statistical analysis and treatment of all data in this study were made of Excel 2007 and SPSS 19 software. The measurement data accords with the normal distribution with mean mean + standard deviation (x + s), and the data between groups are compared with independent sample t test. Analysis; non normal distribution of natural logarithm conversion to conform to normal distribution requirements; data analysis before and after intervention using paired t test analysis; results P0.05 has statistical significance. Results 1. before the treatment of safflower yellow, group A and B general baseline level comparison, the results suggest that serum TG, HDL-C, ox-LDL, 8-iso-PGF2 a, sICAM The levels of -1, IL-6 and TNF- alpha were statistically different between the two groups. After the treatment of 14d, the metabolic indices and biomarkers of the A group were compared before and after treatment. The results showed that the levels of serum ox-LDL, 8-iso-PGF2 a, sICAM-1, TNF- a, IL-6, and the levels of IL-10 and the levels were statistically significant. After the treatment of 14d, the related metabolic indices and biomarkers in the B group were compared. The results showed that the levels of serum ox-LDL, 8-iso-PGF2 a, sICAM-1, TNF- a, IL-6, IL-10 and GPxl were statistically different from those of.4., while.4., IL-10 and GPxl were statistically different in.4.. The difference between the biomarkers was compared between groups. The results showed that the levels of serum sICAM-1, TNF-, IL-6 and 8-iso-PGF2 alpha in the B group decreased more significantly after treatment, and the difference was statistically significant. Conclusion 1. compared to normal weight T2DM combined with AS, the oxidative stress state and inflammatory response of the obese T2DM with AS were more obvious.2. red flower yellow injection. Ejection fluid can reduce the oxidative stress state and inflammatory response level of obese and normal body weight T2DM combined with AS, and may play a more significant role in the obesity T2DM combined with AS. The.3. application of safflower yellow can inhibit oxidative stress and inflammation, may be beneficial to the prevention and control of AS and delay the progression of AS, and thus help to reduce cardiovascular events. Safflower yellow injection may become an effective drug for preventing oxidative stress and inflammatory reaction in obese T2DM and AS patients.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R587.2;R54

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