EPA、DHA改善胰岛素抵抗与改善炎症的相关性研究

发布时间：2017-12-30 22:11

本文关键词：EPA、DHA改善胰岛素抵抗与改善炎症的相关性研究　出处：《河北医科大学》2016年硕士论文　论文类型：学位论文

【摘要】：目的:胰岛素抵抗(insulin resistance,IR)是指胰岛素敏感组织(如脂肪组织、骨骼肌、肝脏)受胰岛素介导的葡萄糖摄取和利用效能减低的一种病理生理状态,为了维持血糖的稳定,机体代偿性的分泌过多胰岛素产生的高胰岛素血症。胰岛素抵抗是多种代谢性疾病(如糖尿病(diabetes mellitus,DM)、肥胖、高脂血症、高血压)发病的共同病理生理基础。目前研究表明,胰岛素抵抗是一种慢性低度炎症反应性疾病,深海鱼油((二十碳五烯酸(eicosapentaenoic acid,EPA)、二十二碳六烯酸(docosahexaenoic acid,DHA))可以改善胰岛素抵抗,但其作用机制尚不十分明确。鱼油是否是通过抗炎作用来减轻胰岛素抵抗的?其抗炎作用机制是什么?与其衍生物消退素和其受体结合后引起的细胞信号途径转导是否有关?为了明确上述问题,我们开展了此项研究。方法:选取河北医科大学第二医院2014年12月至2015年12月就诊的2型糖尿病患者31例。其中,男12例,女19例,年龄32-74岁,平均年龄为56.00±11.15岁。以上受试者入组后即给予深海鱼油胶囊1370mg,2/日(康麦斯牌),规律口服50天。采集受试者服药前、后的空腹静脉血各10ml,并分离血清和血细胞,一部分血清用于检测空腹血糖(Fasting blood glucose,FBG)、空腹胰岛素(Fasting serum insulin,INS)、总胆固醇(total cholesterol,CHOL)、甘油三酯(Triglyceride,TG)、低密度脂蛋白(Low density lipoprotein,LDL)、高密度脂蛋白(High density lipoprotein,HDL),并通过公式计算胰岛素抵抗指数(HOMA-IR)=空腹血糖(FBG/mmol/L)×空腹胰岛素(FINS/m IU/L)/22.5;另一部分血清通过酶联免疫吸附法(Elisa法)测定血清中肿瘤坏死因子(Tumor necrosis factor-α,TNF-α)、前列腺素E2(Prostaglandin E2,PGE2)、脂联素(Adiponectin,APN)、白介素-10(Interleukin-10,IL-10),一部分血细胞用于收集白细胞,收集得来白细胞经裂解后通过酶联免疫吸附法测定趋化样因子受体-1(Chemokine receptor-like 1,Chem R23)、G蛋白偶联受体-32(G Protein-Coupled Receptors32,GPR32)。通过询问病史记录研究对象的一般情况(姓名、性别、年龄、民族、职业、籍贯、现病史、既往史、个人史、家族史)。测量患者身高体重,并通过公示计算患者体重指数(BMI)=体重(kg)/身高(m)2。统计学方法:所获得的数据均采用SPSS13.0统计软件处理,数据用均数±标准差(?x±s)表示,相应的数据指标,配对样本均数比较计算差值,若差值符合正态分布应用配对样本t检验;若差值不符合正态分布,应用配对样本秩和检验方法;各变量间相关分析应用直线相关。P0.05具有统计学意义。结果:1治疗前后血清中EPA、DHA含量治疗前患者血清中EPA含量2772.440±1317.853ug/L,治疗后患者血清中EPA含量是3358.617±1056.035ug/L,治疗后较治疗前升高586.1786ug/L,P0.05,有统计学意义。治疗前患者血清中DHA含量5203.327±2796.883ug/L,治疗后患者血清中DHA含量是6485.397±2875.910ug/L,治疗后较治疗前升高1282.070ug/L,P0.05,有统计学意义,(见表1,图1)。2治疗前后BMI:治疗前患者BMI是27.236±3.234kg/m2,治疗后患者BMI是27.184±3.208kg/m2,P0.05,无统计学意义(见表2)。3治疗前后一般生化指标:3.1空腹血糖:治疗前患者空腹血糖为8.879±2.330mmol/L,治疗后患者空腹血糖为8.111±2.154mmol/L,治疗后较治疗前减低0.768mmol/L,但P0.05,无统计学意义(见表3)。3.2血脂:治疗前患者HDL为2.491±1.462mmol/L,治疗后患者HDL为2.302±1.265mmol/L,P0.05,无统计学意义。治疗前患者LDL为2.681±1.404mmol/L,治疗后患者LDL为3.303±0.953mmol/L,P0.05,无统计学意义。治疗前患者TG为1.988±0.790mmol/L,治疗后患者TG为2.019±0.952mmol/L,P0.05,无统计学意义。治疗前患者CHOL为5.561±1.338mmol/L,治疗后CHOL为5.142±1.232mmol/L,P0.05,无统计学意义(见表3)。3.3空腹胰岛素:治疗前患者空腹胰岛素为9.809±4.016m IU/L,治疗后患者空腹胰岛素为9.148±4.297m IU/L,治疗后较治疗前降低0.661 m IU/L,但P0.05,无统计学意义(见表3)。3.4胰岛素抵抗指数:治疗前患者胰岛素抵抗指数为3.915±2.080,治疗后患者胰岛素抵抗指数为3.257±1.622,治疗后较治疗前降低0.657,P0.05,有统计学意义(见表3,图2)。4治疗前后血清中TNF-α,PGE2,脂联素,IL-10:4.1 TNF-α:治疗前患者血清中TNF-α浓度为65.094±16.385pg/ml,治疗后患者血清中TNF-α浓度为54.107±20.417pg/ml,治疗后较治疗前降低10.989pg/ml,P0.05,有统计学意义(见表4)。4.2 PGE2:治疗前受试者血清中PGE2浓度为432.859±103.159pg/ml,治疗后患者血清中PGE2浓度为394.874±128.851pg/ml,治疗后较治疗前降低37.989pg/ml,P0.05,有统计学意义(见表4)。4.3血清脂联素:治疗前患者血清中脂联素浓度为49.563±40.334pg/ml,治疗后患者血清中脂联素浓度为66.000±41.305pg/ml,治疗后较治疗前升高16.437pg/ml,P0.05,有统计学意义(见表4)。4.4 IL-10:治疗前患者血清中IL-10浓度为32.768±14.937pg/ml,治疗后患者血清中IL-10浓度为35.108±16.233pg/ml,P0.05,无统计学意义(见表4,图3)。5治疗前后白细胞中的Chem R23,GPR32:5.1 Chem R23:治疗前患者白细胞中Chem R23浓度为0.383±0.063%,治疗后患者白细胞中Chem R23浓度为0.477±0.016%,治疗后较治疗前升高0.094%,P0.05,有统计学意义,(见表5)。5.2 GPR32:治疗前患者白细胞中GPR32浓度为0.422±0.070%,治疗后患者白细胞中GPR32浓度为0.465±0.066%,治疗后较治疗前升高0.043%,P0.05,有统计学意义,(见表5,图4)。6相关分析:6.1治疗前后,胰岛素抵抗指数与TNF-α,PGE2均成正相关关系,相关指数分别为0.078,0.210,0.176,0.275,且P0.05,有统计学意义;治疗前后,胰岛素抵抗指数与脂联素,IL-10均呈负相关关系,相关指数分别为-0.327,-0.218,-0.016,-0.112,P0.05,有统计学意义(见表6,7)。6.2治疗前后患者血清中EPA含量差值与治疗前后胰岛素抵抗指数差值呈正相关关系,相关指数为0.023,P0.05,有统计学意义(见表8,图7);治疗前后DHA含量差值与治疗前后胰岛素抵抗指数呈正相关关系,相关指数为0.176,P0.05,有统计学意义(见表9,图8)。6.3治疗前后患者血清中EPA含量差值与TNF-α,PGE2,脂联素,IL-10差值均呈正相关关系,相关系数分别是0.035,0.105,0.113,0.116,P0.05,有统计学意义(见表8,图9-12);治疗前后患者血清中DHA含量差值与TNF-α,PGE2,脂联素,IL-10差值均呈正相关关系,相关系数分别是0.286,0.150,0.072,0.044,P0.05,有统计学意义(见表9,图13-16)。6.4治疗前后患者血清中EPA含量差值与治疗前后患者白细胞中Chem R23差值呈正相关关系,相关系数为0.120,P0.05,有统计学意义(见表8,图17)。6.5治疗前后患者血清中DHA含量差值与患者白细胞中GPR32差值的相关系数为0.430,但P0.05,无统计学意义(见表9,图18)。结论:1口服深海鱼油(EPA、DHA)可使患者血清中EPA、DHA含量升高。2口服深海鱼油(EPA、DHA)后患者血清中促炎因子(TNF-α、PGE2)表达减少,抗炎因子(脂联素、IL-10)表达增加;胰岛素抵抗指数减小。3根据相关性分析可知,胰岛素抵抗是一种慢性低度炎症反应,患者血清中EPA、DHA含量提升值愈大,胰岛素抵抗改善程度愈大,促炎因子降低值愈大,抗炎因子升高值愈大,EPA、DHA可能是通过抗炎作用来减轻胰岛素抵抗的。4消退素是EPA、DHA衍生物,口服深海鱼油(EPA、DHA)后,消退素受体Chem R23,GPR32表达增加,根据相关性分析可知,EPA、DHA含量提升值愈大,炎症改善程度愈大,Chem R23、GPR32含量提升值愈大;EPA、DHA的抗炎作用可能与其代谢产物消退素与受体Chem R23,GPR32结合后,阻断炎症信号通路、抑制炎性因子表达有关。
[Abstract]:Objective: insulin resistance (insulin resistance IR) refers to the insulin sensitive tissues (such as adipose tissue, skeletal muscle, liver) by insulin mediated glucose uptake and utilization efficiency of a reduced state of pathophysiology, in order to maintain the stability of blood sugar, compensatory secretion of excessive insulin produced hyperinsulinemia insulin. Resistance is a variety of metabolic diseases (such as diabetes (diabetes, mellitus, DM), obesity, hyperlipidemia, hypertension) common pathophysiological basis of pathogenesis. The present study showed that insulin resistance is a chronic low-grade inflammatory disease, deep sea fish oil (twenty carbon (five AA (eicosapentaenoic, acid, EPA) twenty-two six carbon acid (docosahexaenoic acid, DHA)) can improve insulin resistance, but its mechanism is not very clear. Whether the anti-inflammatory effects of fish oil to reduce insulin resistance in its anti-inflammatory effect? What is the mechanism? Cell signal transduction and its derivatives fade and its receptor binding caused by the relevant? In order to solve this problem, we carried out this study. Methods: 31 patients with type 2 diabetes from the second hospital of Hebei Medical University from December 2014 to December 2015 were cases. Among them, male 12 cases, female 19 cases, age 32-74 years old, the average age was 56 + 11.15 years old. The above subjects into the group treated by deep sea fish oil capsules 1370mg, 2/ (Con Max Ly), regular oral 50 days. Samples were collected before medication, fasting venous blood after 10ml, the serum and blood cell separation and a part for the detection of fasting serum. Blood glucose (Fasting blood glucose, FBG), fasting insulin (Fasting serum, insulin, INS), total cholesterol (total, cholesterol, CHOL), triglycerides (Triglyceride, TG), low density lipoprotein (Low density, lipoprotein, LDL), high density Lipoprotein (High density, lipoprotein, HDL), and insulin resistance index calculated by the formula (HOMA-IR) = fasting blood glucose (FBG/mmol/L) and fasting insulin (FINS/m IU/L) * /22.5; the other part of the serum by enzyme-linked immunosorbent assay (Elisa) determination of tumor necrosis factor alpha in serum (Tumor necrosis factor-, TNF- alpha), prostaglandin E2 (Prostaglandin E2 PGE2), adiponectin (Adiponectin, APN), interleukin -10 (Interleukin-10, IL-10), part of the blood cells for the collection of white blood cells, we collect white blood cells were lysed by enzyme-linked immunosorbent assay method for the determination of chemotactic factor receptor like -1 (Chemokine receptor-like 1, Chem R23), G protein coupled receptor -32 (G Protein-Coupled Receptors32, GPR32). The general asked the research object records (name, gender, age, nationality, occupation, place of origin, history, past history, personal history, family history). Measuring patient Their height and weight, and body mass index were calculated through publicity (BMI) = weight (kg) / height (m) 2. statistical methods: the data were processed by statistical software SPSS13.0, data with standard deviation (? X + s) said that the corresponding index, mean paired comparison calculate the difference, if the difference with normal distribution using paired sample t test; if the difference does not meet the normal distribution, using the paired Wilcoxon method; statistically significant linear correlation analysis between variables using.P0.05. Results: 1 before and after treatment, serum EPA, DHA content of the serum EPA level before treatment in 2772.440. 1317.853ug/L, after treatment in patients with the content of EPA is 3358.617 + 1056.035ug/L, after treatment than before treatment increased 586.1786ug/L, P0.05, have statistical significance before treatment. The DHA content in serum of 5203.327 + 2796.883ug/L in the serum of patients with DHA after treatment The content is 6485.397 + 2875.910ug/L, after treatment than before treatment increased 1282.070ug/L, P0.05, was statistically significant (Table 1, figure 1) before and after treatment of.2 patients before BMI: treatment BMI was 27.236 + 3.234kg/m2, after treatment of patients with BMI was 27.184 + 3.208kg/m2, P0.05, no statistical significance (Table 2) before and after.3 treatment in general biochemical indexes: 3.1 fasting blood glucose: before treatment, fasting blood glucose was 8.879 + 2.330mmol/L, after treatment, fasting blood glucose was 8.111 + 2.154mmol/L, after treatment than before treatment to reduce 0.768mmol/L, but P0.05 was not statistically significant (see Table 3).3.2 blood lipid: before treatment, patients with HDL was 2.491 + 1.462mmol/L, after treatment of patients with HDL was 2.302 + 1.265mmol/L, P0.05, no statistical significance before treatment. LDL was 2.681 + 1.404mmol/L, after treatment of patients with LDL was 3.303 + 0.953mmol/L, P0.05, no statistical significance before treatment. TG was 1.988 + 0.790mmol/L, after treatment of patients with TG was 2.019 + 0.952mmol/L, P0.05, no statistical significance before treatment. CHOL was 5.561 + 1.338mmol/L, CHOL after treatment was 5.142 + 1.232mmol/L, P0.05, no statistical significance (see Table 3).3.3 fasting insulin: before treatment, the fasting insulin was 9.809 + 4.016m IU/L, after treatment, the fasting insulin was 9.148 + 4.297m IU/L after treatment decreased 0.661 m IU/L, but P0.05 was not statistically significant (see Table 3).3.4 insulin resistance index before treatment with insulin resistance index was 3.915 + 2.080, after treatment of patients with insulin resistance index was 3.257 + 1.622, 0.657 lower after treatment than before treatment, P0.05 was statistically significant (see Table 3. Figure 2) before and after treatment of.4 in serum of TNF- alpha, PGE2, adiponectin, IL-10:4.1 TNF- alpha TNF- alpha: before treatment, serum concentration was 65.094 + 16.385pg/ml, TNF- after treatment in patients with alpha concentration was 54.107 + 20.417pg/ml, after treatment Before the reduction of 10.989pg/ml, P0.05, was statistically significant (see Table 4).4.2 before PGE2: treatment subjects in the serum concentration of PGE2 was 432.859 + 103.159pg/ml, PGE2 after treatment serum concentration was 394.874 + 128.851pg/ml, after treatment than before treatment decreased 37.989pg/ml, P0.05, have statistical significance (see Table 4).4.3 serum adiponectin before treatment in the serum of patients with adiponectin concentration was 49.563 + 40.334pg/ml, after treatment of adiponectin in serum of patients with concentration of 66 + 41.305pg/ml, after treatment than before treatment increased 16.437pg/ml, P0.05, was statistically significant (see Table 4).4.4 IL-10: IL-10 treatment concentration was 32.768 + 14.937pg/ml in serum of patients before and after treatment in patients with IL-10 serum concentration 35.108 + 16.233pg/ml, P0.05, no statistical significance (Table 4, figure 3) Chem R23 in white blood cells before and after.5 treatment, GPR32:5.1 Chem R23: before treatment in white blood cells Chem R23 concentration was 0.383 + 0 63%, after the treatment of white blood cells in patients with Chem R23 concentration was 0.477 + 0.016%, after treatment than before treatment increased 0.094%, P0.05, was statistically significant (see Table 5).5.2 GPR32: in the treatment of the concentration of GPR32 was 0.422 + 0.070% in patients with white blood cells, white blood cells in patients with GPR32 after treatment concentration was 0.465 + 0.066%, treatment after than before treatment increased 0.043%, P0.05, was statistically significant (Table 5, figure 4): 6.1.6 correlation analysis before and after treatment, the insulin resistance index and TNF- alpha, PGE2 were positively correlated, correlation index were 0.078,0.210,0.176,0.275 and P0.05, the difference was statistically significant; after treatment, the insulin resistance index and adiponectin IL-10, there is a negative correlation between the related index, respectively -0.327, -0.218, -0.016, -0.112, P0.05, was statistically significant (see table 6,7).6.2 before and after treatment, the difference between before and after treatment with the EPA content in the serum of patients with insulin resistance index difference was positively correlated And the related index was 0.023, P0.05 was statistically significant (Table 8, Figure 7); the difference between before and after treatment before and after treatment with DHA in insulin resistance index were positively correlated, correlation index was 0.176, P0.05 was statistically significant (Table 9, figure 8).6.3 before and after treatment in patients with serum difference and TNF- alpha the content of EPA in PGE2, adiponectin, IL-10 values are positive correlation, correlation coefficient was 0.035,0.105,0.113,0.116, P0.05 was statistically significant (Table 8, FIG. 9-12) before and after treatment; the DHA content in serum and the difference of TNF- alpha, PGE2, adiponectin, IL-10 values were positively correlated, correlation coefficient was 0.286,0.150,0.072,0.044 P0.05, there was statistical significance (Table 9, figure 13-16).6.4 before and after treatment, the difference between before and after treatment with the EPA content in serum of white blood cells in patients with Chem R23 difference is positive correlation, correlation coefficient was 0.120, P0.05 was statistically significant (Table 8, FIG. 17) before and after treatment of.6.5 correlation coefficient difference of DHA content in serum and white blood cells in patients with GPR32 difference is 0.430, but P0.05 was not statistically significant (Table 9, Figure 18). Conclusion: 1 oral fish oil (EPA, DHA) can be made in the serum of patients with EPA, DHA increased the content of.2 oral fish oil (EPA, DHA) in patients after serum proinflammatory cytokines (TNF- alpha, PGE2) decreased expression of anti-inflammatory factor (adiponectin, IL-10) expression increased; insulin resistance index decreased according to.3 correlation analysis showed that insulin resistance is a chronic inflammatory reaction, patient serum EPA, DHA content and enhance the value of the. The greater the degree of improvement in insulin resistance, reduce proinflammatory factor value is greater, the greater the value increase of anti-inflammatory cytokines, EPA, DHA may be through anti-inflammatory action to reduce insulin resistance in.4 resolvin EPA, DHA oral deep-sea fish oil derivatives (EPA, DHA), regression of hormone receptor Chem R23, expression of GPR32 Increase, according to the results of correlation analysis, EPA, DHA content and enhance the value of larger, greater improvement of inflammation, Chem R23, GPR32 content and enhance the value of the greater; EPA, anti-inflammatory effects may be related to metabolic products of DHA and R23 resolvin Chem receptor, GPR32 binding, blocking the inflammatory signaling pathway, inhibition of inflammatory factor expression relevant.

【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R587.1

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