本文關(guān)鍵詞：EPA、DHA改善胰島素抵抗與改善炎癥的相關(guān)性研究　出處：《河北醫(yī)科大學(xué)》2016年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 深海魚油 EPA DHA 胰島素抵抗 抗炎作用 消退素

【摘要】：目的:胰島素抵抗(insulin resistance,IR)是指胰島素敏感組織(如脂肪組織、骨骼肌、肝臟)受胰島素介導(dǎo)的葡萄糖攝取和利用效能減低的一種病理生理狀態(tài),為了維持血糖的穩(wěn)定,機(jī)體代償性的分泌過多胰島素產(chǎn)生的高胰島素血癥。胰島素抵抗是多種代謝性疾病(如糖尿病(diabetes mellitus,DM)、肥胖、高脂血癥、高血壓)發(fā)病的共同病理生理基礎(chǔ)。目前研究表明,胰島素抵抗是一種慢性低度炎癥反應(yīng)性疾病,深海魚油((二十碳五烯酸(eicosapentaenoic acid,EPA)、二十二碳六烯酸(docosahexaenoic acid,DHA))可以改善胰島素抵抗,但其作用機(jī)制尚不十分明確。魚油是否是通過抗炎作用來減輕胰島素抵抗的?其抗炎作用機(jī)制是什么?與其衍生物消退素和其受體結(jié)合后引起的細(xì)胞信號(hào)途徑轉(zhuǎn)導(dǎo)是否有關(guān)?為了明確上述問題,我們開展了此項(xiàng)研究。方法:選取河北醫(yī)科大學(xué)第二醫(yī)院2014年12月至2015年12月就診的2型糖尿病患者31例。其中,男12例,女19例,年齡32-74歲,平均年齡為56.00±11.15歲。以上受試者入組后即給予深海魚油膠囊1370mg,2/日(康麥斯牌),規(guī)律口服50天。采集受試者服藥前、后的空腹靜脈血各10ml,并分離血清和血細(xì)胞,一部分血清用于檢測(cè)空腹血糖(Fasting blood glucose,FBG)、空腹胰島素(Fasting serum insulin,INS)、總膽固醇(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),并通過公式計(jì)算胰島素抵抗指數(shù)(HOMA-IR)=空腹血糖(FBG/mmol/L)×空腹胰島素(FINS/m IU/L)/22.5;另一部分血清通過酶聯(lián)免疫吸附法(Elisa法)測(cè)定血清中腫瘤壞死因子(Tumor necrosis factor-α,TNF-α)、前列腺素E2(Prostaglandin E2,PGE2)、脂聯(lián)素(Adiponectin,APN)、白介素-10(Interleukin-10,IL-10),一部分血細(xì)胞用于收集白細(xì)胞,收集得來白細(xì)胞經(jīng)裂解后通過酶聯(lián)免疫吸附法測(cè)定趨化樣因子受體-1(Chemokine receptor-like 1,Chem R23)、G蛋白偶聯(lián)受體-32(G Protein-Coupled Receptors32,GPR32)。通過詢問病史記錄研究對(duì)象的一般情況(姓名、性別、年齡、民族、職業(yè)、籍貫、現(xiàn)病史、既往史、個(gè)人史、家族史)。測(cè)量患者身高體重,并通過公示計(jì)算患者體重指數(shù)(BMI)=體重(kg)/身高(m)2。統(tǒng)計(jì)學(xué)方法:所獲得的數(shù)據(jù)均采用SPSS13.0統(tǒng)計(jì)軟件處理,數(shù)據(jù)用均數(shù)±標(biāo)準(zhǔn)差(?x±s)表示,相應(yīng)的數(shù)據(jù)指標(biāo),配對(duì)樣本均數(shù)比較計(jì)算差值,若差值符合正態(tài)分布應(yīng)用配對(duì)樣本t檢驗(yàn);若差值不符合正態(tài)分布,應(yīng)用配對(duì)樣本秩和檢驗(yàn)方法;各變量間相關(guān)分析應(yīng)用直線相關(guān)。P0.05具有統(tǒng)計(jì)學(xué)意義。結(jié)果:1治療前后血清中EPA、DHA含量治療前患者血清中EPA含量2772.440±1317.853ug/L,治療后患者血清中EPA含量是3358.617±1056.035ug/L,治療后較治療前升高586.1786ug/L,P0.05,有統(tǒng)計(jì)學(xué)意義。治療前患者血清中DHA含量5203.327±2796.883ug/L,治療后患者血清中DHA含量是6485.397±2875.910ug/L,治療后較治療前升高1282.070ug/L,P0.05,有統(tǒng)計(jì)學(xué)意義,(見表1,圖1)。2治療前后BMI:治療前患者BMI是27.236±3.234kg/m2,治療后患者BMI是27.184±3.208kg/m2,P0.05,無統(tǒng)計(jì)學(xué)意義(見表2)。3治療前后一般生化指標(biāo):3.1空腹血糖:治療前患者空腹血糖為8.879±2.330mmol/L,治療后患者空腹血糖為8.111±2.154mmol/L,治療后較治療前減低0.768mmol/L,但P0.05,無統(tǒng)計(jì)學(xué)意義(見表3)。3.2血脂:治療前患者HDL為2.491±1.462mmol/L,治療后患者HDL為2.302±1.265mmol/L,P0.05,無統(tǒng)計(jì)學(xué)意義。治療前患者LDL為2.681±1.404mmol/L,治療后患者LDL為3.303±0.953mmol/L,P0.05,無統(tǒng)計(jì)學(xué)意義。治療前患者TG為1.988±0.790mmol/L,治療后患者TG為2.019±0.952mmol/L,P0.05,無統(tǒng)計(jì)學(xué)意義。治療前患者CHOL為5.561±1.338mmol/L,治療后CHOL為5.142±1.232mmol/L,P0.05,無統(tǒng)計(jì)學(xué)意義(見表3)。3.3空腹胰島素:治療前患者空腹胰島素為9.809±4.016m IU/L,治療后患者空腹胰島素為9.148±4.297m IU/L,治療后較治療前降低0.661 m IU/L,但P0.05,無統(tǒng)計(jì)學(xué)意義(見表3)。3.4胰島素抵抗指數(shù):治療前患者胰島素抵抗指數(shù)為3.915±2.080,治療后患者胰島素抵抗指數(shù)為3.257±1.622,治療后較治療前降低0.657,P0.05,有統(tǒng)計(jì)學(xué)意義(見表3,圖2)。4治療前后血清中TNF-α,PGE2,脂聯(lián)素,IL-10:4.1 TNF-α:治療前患者血清中TNF-α濃度為65.094±16.385pg/ml,治療后患者血清中TNF-α濃度為54.107±20.417pg/ml,治療后較治療前降低10.989pg/ml,P0.05,有統(tǒng)計(jì)學(xué)意義(見表4)。4.2 PGE2:治療前受試者血清中PGE2濃度為432.859±103.159pg/ml,治療后患者血清中PGE2濃度為394.874±128.851pg/ml,治療后較治療前降低37.989pg/ml,P0.05,有統(tǒng)計(jì)學(xué)意義(見表4)。4.3血清脂聯(lián)素:治療前患者血清中脂聯(lián)素濃度為49.563±40.334pg/ml,治療后患者血清中脂聯(lián)素濃度為66.000±41.305pg/ml,治療后較治療前升高16.437pg/ml,P0.05,有統(tǒng)計(jì)學(xué)意義(見表4)。4.4 IL-10:治療前患者血清中IL-10濃度為32.768±14.937pg/ml,治療后患者血清中IL-10濃度為35.108±16.233pg/ml,P0.05,無統(tǒng)計(jì)學(xué)意義(見表4,圖3)。5治療前后白細(xì)胞中的Chem R23,GPR32:5.1 Chem R23:治療前患者白細(xì)胞中Chem R23濃度為0.383±0.063%,治療后患者白細(xì)胞中Chem R23濃度為0.477±0.016%,治療后較治療前升高0.094%,P0.05,有統(tǒng)計(jì)學(xué)意義,(見表5)。5.2 GPR32:治療前患者白細(xì)胞中GPR32濃度為0.422±0.070%,治療后患者白細(xì)胞中GPR32濃度為0.465±0.066%,治療后較治療前升高0.043%,P0.05,有統(tǒng)計(jì)學(xué)意義,(見表5,圖4)。6相關(guān)分析:6.1治療前后,胰島素抵抗指數(shù)與TNF-α,PGE2均成正相關(guān)關(guān)系,相關(guān)指數(shù)分別為0.078,0.210,0.176,0.275,且P0.05,有統(tǒng)計(jì)學(xué)意義;治療前后,胰島素抵抗指數(shù)與脂聯(lián)素,IL-10均呈負(fù)相關(guān)關(guān)系,相關(guān)指數(shù)分別為-0.327,-0.218,-0.016,-0.112,P0.05,有統(tǒng)計(jì)學(xué)意義(見表6,7)。6.2治療前后患者血清中EPA含量差值與治療前后胰島素抵抗指數(shù)差值呈正相關(guān)關(guān)系,相關(guān)指數(shù)為0.023,P0.05,有統(tǒng)計(jì)學(xué)意義(見表8,圖7);治療前后DHA含量差值與治療前后胰島素抵抗指數(shù)呈正相關(guān)關(guān)系,相關(guān)指數(shù)為0.176,P0.05,有統(tǒng)計(jì)學(xué)意義(見表9,圖8)。6.3治療前后患者血清中EPA含量差值與TNF-α,PGE2,脂聯(lián)素,IL-10差值均呈正相關(guān)關(guān)系,相關(guān)系數(shù)分別是0.035,0.105,0.113,0.116,P0.05,有統(tǒng)計(jì)學(xué)意義(見表8,圖9-12);治療前后患者血清中DHA含量差值與TNF-α,PGE2,脂聯(lián)素,IL-10差值均呈正相關(guān)關(guān)系,相關(guān)系數(shù)分別是0.286,0.150,0.072,0.044,P0.05,有統(tǒng)計(jì)學(xué)意義(見表9,圖13-16)。6.4治療前后患者血清中EPA含量差值與治療前后患者白細(xì)胞中Chem R23差值呈正相關(guān)關(guān)系,相關(guān)系數(shù)為0.120,P0.05,有統(tǒng)計(jì)學(xué)意義(見表8,圖17)。6.5治療前后患者血清中DHA含量差值與患者白細(xì)胞中GPR32差值的相關(guān)系數(shù)為0.430,但P0.05,無統(tǒng)計(jì)學(xué)意義(見表9,圖18)。結(jié)論:1口服深海魚油(EPA、DHA)可使患者血清中EPA、DHA含量升高。2口服深海魚油(EPA、DHA)后患者血清中促炎因子(TNF-α、PGE2)表達(dá)減少,抗炎因子(脂聯(lián)素、IL-10)表達(dá)增加;胰島素抵抗指數(shù)減小。3根據(jù)相關(guān)性分析可知,胰島素抵抗是一種慢性低度炎癥反應(yīng),患者血清中EPA、DHA含量提升值愈大,胰島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可能是通過抗炎作用來減輕胰島素抵抗的。4消退素是EPA、DHA衍生物,口服深海魚油(EPA、DHA)后,消退素受體Chem R23,GPR32表達(dá)增加,根據(jù)相關(guān)性分析可知,EPA、DHA含量提升值愈大,炎癥改善程度愈大,Chem R23、GPR32含量提升值愈大;EPA、DHA的抗炎作用可能與其代謝產(chǎn)物消退素與受體Chem R23,GPR32結(jié)合后,阻斷炎癥信號(hào)通路、抑制炎性因子表達(dá)有關(guān)。
[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.

【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R587.1

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