發(fā)布時間：2018-05-26 05:01

  本文選題：2型糖尿病 + 動脈粥樣硬化　； 參考：《山東大學》2017年碩士論文

【摘要】：研究背景近年來,隨著經(jīng)濟的發(fā)展以及現(xiàn)代生活方式的改變,2型糖尿病、肥胖等代謝性疾病的患病率呈快速上升趨勢,給人類健康帶來極大威脅。T2DM可引起全身各個系統(tǒng)和重要器官的病變,導致心血管事件、腦卒中、終末期腎臟疾病、失明等嚴重并發(fā)癥,致殘及致死率高,其中心血管并發(fā)癥是其的最主要死因。T2DM發(fā)病率的增長與全球性肥胖的流行直接相關,腹型肥胖作為代謝綜合征臨床表現(xiàn)的組成部分,代謝紊亂是其突出臨床特點,增加了患者發(fā)展為T2DM和動脈粥樣硬化性大血管病的風險。隨著肥胖發(fā)病率的日益增加,肥胖T2DM患者比例也迅速升高,其動脈粥樣硬化的發(fā)生率也迅速上升。T2DM及肥胖這兩個心腦血管事件的獨立危險因素合并存在,極大地增加了機體代謝紊亂的復雜性,提高了 T2DM患者大血管病變的發(fā)生率,同時也加重了病情嚴重程度和不良預后,給T2DM的臨床診治工作帶來嚴峻挑戰(zhàn)。因此充分認識肥胖T2DM合并大血管病變患者的臨床特點,才能在當前診療經(jīng)驗基礎上更有的放矢的進行治療,延緩病情進展。如何更能有效的治療并改善T2DM合并AS及肥胖患者預后,降低死亡率是當前臨床治療及研究的熱點及難點。現(xiàn)階段T2DM的臨床常規(guī)治療主要為降糖、調(diào)脂、抗凝、降壓、改善循環(huán)等。T2DM時的慢性高血糖狀態(tài)已被證實主要是通過氧化應激、炎癥反應和胰島素抵抗來影響機體功能,因此在上述常規(guī)治療手段外,針對這些可能的病理生理改變的治療方法也逐漸在臨床上應用,并證實有效。近些年的大量研究發(fā)現(xiàn)上述病理生理改變可能為T2DM、肥胖和AS的共同發(fā)病機制,因此相關抗炎、抗氧化治療有望在肥胖T2DM合并AS患者治療中取得較好療效。研究目的本研究主要目的是探討肥胖和正常體重T2DM合并AS者氧化應激及炎癥反應狀態(tài)的變化特點,并探討紅花黃色素治療對T2DM合并AS者氧化應激及炎癥反應有關指標的影響,進而評價紅花黃色素抗氧化應激及炎癥反應的臨床應用價值。研究方法研究對象:通過以下入排標準招募研究對象,進而盡可能控制影響氧化應激和炎癥反應水平的其他混雜因素。選擇2015.10.01-2016.07.01于齊魯醫(yī)院門診就診及住院的T2DM合并AS患者117例(男58例,女59例),臨床資料均完備。根據(jù)BMI將患者分為正常體重組(BMI24)(A組,60例)和肥胖組(BMI≥28)(B組,57例),其中A組男性31人,女性29人,平均年齡,60.41±5.65歲。B組男性27人,女性30人,平均年齡59.11 ±4.81歲。納入標準:①確診為T2DM,診斷標準參照1999年WHO制定的糖尿病診斷標準;②頸動脈或下肢動脈超聲檢查發(fā)現(xiàn)動脈粥樣硬化性斑塊者;③年齡45-76周歲者,性別不限;④糖化血紅蛋白GHbAlc7%,血糖控制達標者,以排除血糖水平對氧化應激及炎癥水平的影響;⑤血壓140/90mmHg,以排除血壓水平對氧化應激及炎癥水平的影響;⑥患者及其家屬知情同意。排除標準:①有腦卒中、心肌梗死及其他大血管栓塞病史者;②重大外傷手術史、移植史、腫瘤、燒傷等應激狀態(tài)者;③伴有嚴重的肝腎臟疾病者,如急、慢性肝、腎功能不全或衰竭等;④有急、慢性感染疾病證據(jù);⑤有免疫疾病,如慢性結(jié)締組織病、AIDS等;⑥近期服用抗炎或是免疫抑制藥物;⑦有藥物或酒精依賴史或精神疾病史。資料收集:①收集所有患者的一般臨床情況,主要包括年齡、性別、體重、身高、腹圍、煙酒史、常見慢性病史、傳染病史、手術及外傷史、家族史、女性詢問月經(jīng)及婚育史,并計算體重質(zhì)量指數(shù)BMI(Kg/m2)=體重(Kg)/身高2(m2)。②患者給予一般常規(guī)的降糖、降壓、調(diào)脂等治療后,給予紅花黃色素注射液治療14d,并分別于治療前后,檢測受試者空腹血清血脂、ox-LDL、8-iso-PGF2α、sICAM-1、IL-6、TNF-α、GPxl 和 IL-10 水平。統(tǒng)計方法:本研究中所有數(shù)據(jù)的統(tǒng)計分析及處理采用Excel 2007及SPSS 19.0軟件。計量資料符合正態(tài)分布者以均數(shù)±標準差(x±s)表示,組間數(shù)據(jù)比較用獨立樣本t檢驗分析;非正態(tài)分布者采取自然對數(shù)轉(zhuǎn)換為符合正態(tài)分布要求;干預治療前后數(shù)據(jù)分析采用配對t檢驗分析;結(jié)果中p0.05有統(tǒng)計學意義。研究結(jié)果1.紅花黃色素治療前,A組和B組一般情況基線水平比較,結(jié)果提示血清TG、HDL-C、ox-LDL、8-iso-PGF2α、sICAM-1、IL-6 和 TNF-α 水平在兩組之間有統(tǒng)計學差異。2.紅花黃色素治療14d后,對A組患者治療前后相關代謝指標及生物標志物進行比較,比較結(jié)果顯示治療后血清ox-LDL、8-iso-PGF2α、sICAM-1、TNF-α、IL-6、IL-10和GPxl的水平變化具有統(tǒng)計學意義。3.紅花黃色素治療14d后,對B組患者治療前后相關代謝指標及生物標志物進行比較,比較結(jié)果顯示治療后血清ox-LDL、8-iso-PGF2α、sICAM-1、TNF-α、IL-6、IL-10和GPxl的水平變化有統(tǒng)計學差異。4.紅花黃色素治療14d后,對A組和B組患者在治療前后相關代謝指標及生物標志物的差值進行組間比較,結(jié)果顯示在治療后B組血清sICAM-1、TNF-α、IL-6和8-iso-PGF2 α水平降低更顯著,差異具有統(tǒng)計學意義。研究結(jié)論1.相較于正常體重T2DM合并AS者,肥胖T2DM合并AS者的氧化應激狀態(tài)及炎癥反應更明顯。2.紅花黃色素注射液可降低肥胖及正常體重T2DM合并AS者的氧化應激狀態(tài)及炎癥反應水平,并可能在肥胖T2DM合并AS者中的作用更為顯著。3.應用紅花黃色素可以抑制氧化應激和炎癥反應,可能有利于防治AS并延緩AS的進展,進而有利于減少心腦血管事件的發(fā)生率。紅花黃注射液有可能成為臨床肥胖T2DM合并AS者防治氧化應激及炎癥反應的有效藥物。
[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.
【學位授予單位】：山東大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R587.2;R54

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