本文關(guān)鍵詞： 鐵過(guò)載 2型糖尿病 氧化應(yīng)激 一氧化氮 鐵調(diào)素　出處：《河北師范大學(xué)》2015年碩士論文　論文類型：學(xué)位論文

【摘要】：人體和動(dòng)物模型的研究均表明機(jī)體鐵超載是糖尿病發(fā)病的危險(xiǎn)因素。亞鐵離子是助氧化劑,催化細(xì)胞反應(yīng),導(dǎo)致活性氧產(chǎn)生,增加氧化應(yīng)激水平,引起組織損傷。流行病學(xué)研究發(fā)現(xiàn),2型糖尿病(T2DM)患者血清鐵蛋白(SF)含量明顯高于非T2DM人群。SF濃度與血清胰島素、血糖、高血壓、血脂異常及肥胖程度呈正相關(guān)。有氧運(yùn)動(dòng)可顯著增加機(jī)體供能物質(zhì)代謝水平,目前廣泛應(yīng)用于T2DM等代謝性疾病的預(yù)防和治療。有氧運(yùn)動(dòng)是否會(huì)通過(guò)調(diào)控機(jī)體鐵動(dòng)態(tài)平衡而防治T2DM,目前尚不清楚。本研究主要探討有氧運(yùn)動(dòng)在T2DM發(fā)病過(guò)程中,對(duì)大鼠鐵代謝和胰島素抵抗的改善作用,以及相關(guān)鐵代謝調(diào)控因子鐵調(diào)素與一氧化氮含量的變化。闡明有氧運(yùn)動(dòng)通過(guò)調(diào)控機(jī)體鐵代謝而防治T2DM發(fā)生的機(jī)制,為早期預(yù)防和治療T2DM提供理論依據(jù)。研究?jī)?nèi)容與方法:24只12月齡SD大鼠,隨機(jī)分為對(duì)照組(C組)、高糖高脂膳食組(H組)、高糖高脂膳食結(jié)合有氧運(yùn)動(dòng)組(HE組),每組8只。C組進(jìn)行基礎(chǔ)飼料喂養(yǎng),其余兩組使用高糖高脂飼料,高糖高脂飼料配方為豬油10%、蔗糖20%、蛋黃粉8%、膽酸鈉0.1%、基礎(chǔ)飼料61.9%(AIN-93G),河北省動(dòng)物實(shí)驗(yàn)中心制作提供。高糖高脂飼料中礦物質(zhì)鐵含量與基礎(chǔ)飼料相同(含鐵100 mg/kg)。HE組在2W適應(yīng)運(yùn)動(dòng)后,進(jìn)行15m/min、45min/d、坡度5、6d/w、3W有氧運(yùn)動(dòng)干預(yù),其余兩組安靜喂養(yǎng)。5周后,用酶聯(lián)免疫吸附實(shí)驗(yàn)(Elisa)檢測(cè)SF、血清胰島素、肝臟八羥基脫氧鳥苷;逆轉(zhuǎn)錄-聚合酶鏈反應(yīng)(RT-PCR)測(cè)量肝臟Hepcidin m RNA含量;生化試劑盒檢測(cè)血清鐵、血清總鐵結(jié)合力、肝組織鐵、血糖、高密度脂蛋白、總膽固醇、肝超氧化物歧化酶(SOD)、肝丙二醛(MDA)、肝過(guò)氧化氫酶(CAT)、血清一氧化氮(NO)、肝臟NO、肝臟膽堿酯酶、血常規(guī);肝組織切片用蘇木精-伊紅(HE)染色。研究結(jié)果:(1)5周高糖高脂膳食誘導(dǎo)H組大鼠血糖升高,罹患T2DM。各組大鼠5周后體重均有所增加,H組較C組和HE組體重增加更為顯著(P0.01)。(2)各組大鼠糖脂代謝狀態(tài):H組和HE組胰島素抵抗指數(shù)、血清胰島素、血糖均高于C組(P0.01,P0.05),HE組胰島素抵抗指數(shù)、血清胰島素、血糖顯著低于H組(P0.01)。H組和HE組胰島素敏感指數(shù)均低于C組(P0.01),HE組胰島素敏感指數(shù)顯著高于H組(P0.01)。H組低密度脂蛋白含量顯著高于C組,HE組低密度脂蛋白含量顯著低于H組(P0.01)。HE組和C組高密度脂蛋白含量均高于H組(P0.01,P0.05)。(3)各組大鼠機(jī)體鐵狀態(tài)變化:H組血清鐵、轉(zhuǎn)鐵蛋白飽和度、肝組織鐵顯著高于C組和HE組(P0.01,P0.05);H組和HE組SF均顯著高于C組(P0.01),HE組SF顯著低于H組(P0.01)。線性回歸分析顯示血糖和血清鐵蛋白呈線性正相關(guān)。(4)各組大鼠氧化應(yīng)激與肝細(xì)胞損傷程度:H組肝SOD、肝CAT顯著低于C組和HE組(P0.01,P0.05),HE組和C組MDA顯著低于H組(P0.01)。H組白細(xì)胞含量顯著高于C組(P0.01),HE組白細(xì)胞含量低于H組(P0.05)。H組和HE組血紅蛋白濃度顯著低于C組(P0.01,P0.05)。(5)各組大鼠肝臟組織形態(tài)學(xué)改變:H組肝細(xì)胞混合性大、小泡脂變,大泡脂變脂滴大,核偏移,且小灶狀炎癥細(xì)胞浸潤(rùn),少數(shù)細(xì)胞凋亡,核固縮。HE組少量肝細(xì)胞小泡性脂肪變,細(xì)胞核居中,胞質(zhì)內(nèi)充滿微小脂滴。與H組肝細(xì)胞相較,HE組肝脂肪變較輕,且無(wú)炎癥細(xì)胞浸潤(rùn)和細(xì)胞凋亡。(6)鐵代謝調(diào)控因子表達(dá)量變化:H組Hepcidin m RNA顯著高于C組(P0.05),HE組Hepcidin m RNA顯著低于H組(P0.01)。H組血清NO和肝臟NO含量顯著高于C組,HE組血清NO和肝臟NO含量顯著低于H組(P0.01)。結(jié)論:(1)長(zhǎng)期高糖高脂飲食誘導(dǎo)大鼠體重增加,加重鐵過(guò)載和氧化應(yīng)激,出現(xiàn)胰島素抵抗。實(shí)驗(yàn)結(jié)果表明,通過(guò)對(duì)自然衰老大鼠進(jìn)行高糖高脂飼料喂養(yǎng),大鼠血糖超過(guò)11.1mmol/L,2型糖尿病造模成功。(2)有氧運(yùn)動(dòng)降低機(jī)體鐵儲(chǔ)存,增加抗氧化應(yīng)激酶的活性,緩解氧化應(yīng)激與胰島素抵抗,減輕高脂膳食大鼠肝組織脂肪樣變,預(yù)防2型糖尿病的發(fā)生。(3)長(zhǎng)期有氧運(yùn)動(dòng)通過(guò)降低大鼠的NO和Hepcidin含量,控制炎癥反應(yīng),促進(jìn)肝鐵釋放,緩解鐵過(guò)載,穩(wěn)定鐵狀態(tài)。適度運(yùn)動(dòng)能夠降低大鼠體內(nèi)對(duì)高糖高脂飼料刺激產(chǎn)生過(guò)量的NO和Hepcidin,并維持在正常的生理范圍內(nèi)。
[Abstract]:The study of human and animal models indicate that body iron overload is a risk factor for the onset of diabetes. The ferrous ion is co oxidant, catalytic reaction cell, resulting in the generation of reactive oxygen species, increase the level of oxidative stress, causing damage to tissue. Epidemiological studies have found that type 2 diabetes mellitus (T2DM) patients with serum ferritin (SF) was significantly higher than that of non T2DM in.SF concentration and serum insulin, blood glucose, hypertension, dyslipidemia and obesity was positively related to the degree. Aerobic exercise can significantly increase the body energy metabolism level, prevention and treatment has been widely used in T2DM and other metabolic diseases. Aerobic exercise is through regulation of iron homeostasis and control of T2DM, it is not clear. This study focused on the aerobic exercise in the pathogenesis of T2DM, to improve the role of iron metabolism and insulin resistance in rats, as well as related to iron metabolism regulation of hepcidin and a factor The changes of nitric oxide content. The aerobic exercise regulation of iron metabolism and prevent the occurrence of T2DM through the mechanism, to provide theoretical basis for early prevention and treatment of T2DM. The research contents and methods: 24 12 month old SD rats were randomly divided into control group (C group), high-fat diet group (H group), high glucose the high-fat diet combined with aerobic exercise group (HE group),.C group with 8 rats in each group were fed basic diet, the other two groups with high glucose and high fat diet, high-fat feed formula for lard 10%, 20% sucrose, 8% yolk powder, 0.1% sodium cholate, 61.9% basic feed (AIN-93G), Hebei province animal experiment center provide basis and content of iron minerals. High glucose and high fat diet in the same feed (FE 100 mg/kg) in the.HE group 2W adaptation after exercise, 15m/min, 45min/d, 5,6d/w, 3W grade, aerobic exercise intervention, the other two groups fed quiet after.5 weeks, using enzyme-linked immunosorbent assay (Elisa) detection of SF. Blood 娓呰儼宀涚礌,鑲濊剰鍏緹鍩鴻劚姘ч笩鑻，

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