本文選題：脂素 + 糖尿病�。� 參考：《山東大學(xué)》2015年碩士論文

【摘要】：研究背景：糖尿病周?chē)窠?jīng)病變(diabetic peripheral neuropathy, DPN)是糖尿病(diabetic mellitus, DM)最常見(jiàn)的慢性并發(fā)癥之一,其患病率達(dá)50%,是造成糖尿病足和截肢的主要原因,嚴(yán)重影響患者的生活質(zhì)量,目前臨床上尚無(wú)有效的治療方法。目前對(duì)DPN發(fā)病機(jī)制的研究多集中在多元醇通路的代謝異常、糖基化終末產(chǎn)物(AGEs)的積聚、氧化應(yīng)激、神經(jīng)營(yíng)養(yǎng)因子等。脂素(Lipin)由脂素基因(LPIN)表達(dá)產(chǎn)生,是一種新發(fā)現(xiàn)的具有雙向調(diào)控功能的一個(gè)家族,可調(diào)控身體脂肪代謝,主要包括Lipin 1、Lipin2和Lipin3。脂素Lipin1作為一種新的脂肪因子,在機(jī)體糖脂代謝中起著重要作用。Lipin1主要表達(dá)于白色脂肪組織及肌肉,同時(shí)也表達(dá)于其他組織如周?chē)窠?jīng)、肝臟及腎臟。有研究發(fā)現(xiàn)Lipin1缺乏是造成周?chē)窠?jīng)病變的原因之一,主要機(jī)制在于Lipin1缺乏導(dǎo)致構(gòu)成神經(jīng)外膜的脂肪墊以及雪旺細(xì)胞中的磷脂酸磷酸酯酶活性缺乏,髓磷脂合成減少,神經(jīng)傳導(dǎo)速度減慢。研究目的：本研究通過(guò)構(gòu)建糖尿病周?chē)窠?jīng)病變大鼠模型,將攜帶Lipin1的慢病毒載體轉(zhuǎn)染糖尿病大鼠,觀察糖尿病大鼠坐骨神經(jīng)的神經(jīng)電生理及病理形態(tài)學(xué)變化,探討Lipin1對(duì)糖尿病大鼠周?chē)窠?jīng)早期病變的影響。方法：36只雄性Wistar大鼠高糖高脂飼料喂養(yǎng)8周后給予小劑量(30 mg/kg)鏈脲佐菌素(STZ)腹腔注射,成功誘導(dǎo)其成為2型糖尿病(type2 diabetes mellitus, T2DM)大鼠模型,隨機(jī)分為空載體組、Lipin1過(guò)表達(dá)組,另選擇12只健康大鼠作為正常對(duì)照組。Lipin1過(guò)表達(dá)(LV-Lipin1)組、空載體(LV-contro1)組分別通過(guò)尾靜脈注射lipin1慢病毒載體(5x107TU)和空慢病毒載體(5×107 TU),每月1次,連續(xù)2次。8周后對(duì)照觀察各組大鼠血糖(BG)、體質(zhì)量(BW)；應(yīng)用甲苯胺藍(lán)染色,通過(guò)光鏡及透射電鏡觀察坐骨神經(jīng)病理形態(tài)學(xué)改變；應(yīng)用免疫組化法測(cè)定Lipin1表達(dá)。數(shù)據(jù)均采用應(yīng)用SPSS 19.0統(tǒng)計(jì)軟件,計(jì)量資料采用x±s,多組間數(shù)據(jù)比較采用單因素方差分析,兩兩比較采用SNK法,P0.05為差異有統(tǒng)汁學(xué)意義。結(jié)果：1.體重和血糖至干預(yù)結(jié)束時(shí),正常組體質(zhì)量呈生理性正常加重,血糖正常�？蛰d體組大鼠血糖高于正常組,其差異有統(tǒng)計(jì)學(xué)意義(P0.05)。Lipin1過(guò)表達(dá)組血糖、體質(zhì)量較空載體組無(wú)顯著差異(P0.05)。2.Lipin1在大鼠坐骨神經(jīng)中的表達(dá)糖尿病大鼠成模2月時(shí),免疫組化觀察坐骨神經(jīng)Lipin1表達(dá),空載體組較正常對(duì)照組坐骨神經(jīng)縱切面Lipin1表達(dá)量明顯減少；Lipin1過(guò)表達(dá)組較空載體組Lipin1表達(dá)量明顯增多。3.神經(jīng)傳導(dǎo)速度糖尿病大鼠造模后4w即可出現(xiàn)神經(jīng)傳導(dǎo)速度減慢,Lipin1轉(zhuǎn)染后8周,Lipin1過(guò)表達(dá)組神經(jīng)傳導(dǎo)速度較空載體組明顯改善(P0.05)。4.對(duì)糖尿病大鼠病理改變的影響糖尿病大鼠造模后8w,空載體組較正常對(duì)照組的神經(jīng)纖維直徑、密度、面積均減少,Lipin1過(guò)表達(dá)組以上病變較空載體組顯著減輕(P0.05)。結(jié)論：1.實(shí)驗(yàn)性糖尿病大鼠成模后4w發(fā)現(xiàn)周?chē)窠?jīng)病變,隨病程延長(zhǎng)神經(jīng)損傷逐漸加重。2.糖尿病周?chē)窠?jīng)病變大鼠坐骨神經(jīng)中Lipin1表達(dá)降低,上調(diào)Lipin1表達(dá)后糖尿病大鼠坐骨神經(jīng)神經(jīng)傳導(dǎo)速度改善,病理學(xué)觀察中亦可見(jiàn)到神經(jīng)髓鞘結(jié)構(gòu)和軸突形態(tài)的改善。
[Abstract]:Background: diabetic peripheral neuropathy (DPN) is one of the most common chronic complications of diabetes (diabetic mellitus, DM). Its prevalence rate is 50%. It is the main cause of diabetic foot and amputation, which seriously affects the living quality of patients. At present, there is no effective treatment in clinical. The research on the pathogenesis of DPN mainly focuses on the metabolic abnormality of the polyol pathway, the accumulation of glycosylated end products (AGEs), oxidative stress, neurotrophic factor, and so on. Lipoprotein (Lipin) is produced by the expression of the lipoprotein gene (LPIN). It is a newly discovered family with bi-directional regulation function, which can regulate body fat metabolism, mainly including Lipin 1, Lipi N2 and Lipin3. lipoprotein Lipin1, as a new fat factor, play an important role in the metabolism of glycolipid,.Lipin1 is mainly expressed in white adipose tissue and muscles, but also in other tissues such as peripheral nerve, liver and kidney. It is found that the lack of Lipin1 is one of the causes of peripheral neuropathy, and the main mechanism is Li Pin1 deficiency leads to the lipid pads that constitute the outer membrane of the nerve and the deficiency of phosphatidate phosphatidase activity in the Schwann cells, the decrease of the synthesis of myelin and the slow speed of nerve conduction. The effect of Lipin1 on the early pathological changes of peripheral nerve in diabetic rats. Methods: 36 male Wistar rats were fed with high glucose and high fat diet for 8 weeks, and a small dose (30 mg/kg) of streptozotocin (STZ) was intraperitoneally injected, and it was successfully induced to become type 2 diabetes mellitus (type2 diabetes mel). Litus, T2DM) rat model, randomly divided into empty carrier group, Lipin1 overexpression group, and 12 healthy rats as normal control group.Lipin1 overexpression (LV-Lipin1) group, LV-contro1 group via tail vein injection of lipin1 lentivirus carrier (5x107TU) and empty lentivirus vector (5 x 107 TU), 1 times a month, 2 consecutive.8 weeks after the control view The blood glucose (BG) and body mass (BW) were observed in each group. The pathological changes of the sciatic nerve were observed with toluidine blue, and the expression of Lipin1 was measured by the light microscopy and transmission electron microscopy. The data were used to use the SPSS 19 statistical software, the measurement data were x s, and the data of multiple groups were compared with the single factor analysis of variance, 22 The SNK method was used to compare the significance of P0.05. Results: when 1. body weight and blood sugar were at the end of the intervention, the normal body mass showed normal weight and normal blood sugar. The blood glucose in the no-load group was higher than that of the normal group. The difference was statistically significant (P0.05).Lipin1 overexpression group blood glucose, and there was no significant difference between the body mass and the empty carrier group (P0.05). The expression of Lipin1 in the sciatic nerve was observed by.2.Lipin1 in the rat model of sciatic nerve in the rat's sciatic nerve in February. The expression of Lipin1 expression in the longitudinal section of the sciatic nerve was significantly reduced in the no-load group than in the normal control group, and the expression of Lipin1 in the Lipin1 overexpression group was significantly increased by the.3. nerve conduction velocity diabetic rat model. The nerve conduction velocity decreased after 4W, 8 weeks after Lipin1 transfection, the nerve conduction velocity in the Lipin1 overexpression group was significantly improved (P0.05).4. on the pathological changes of diabetic rats, and 8W in the diabetic rats. The diameter, density, and area of Lipin1 overexpression group were lower than those in the normal control group. In 1. experimental diabetic rats, 4W found peripheral neuropathy in 1. experimental diabetic rats and gradually increased the Lipin1 expression in the sciatic nerve of rats with.2. diabetic peripheral neuropathy with the duration of the disease, and the increase of the nerve conduction velocity of the sciatic nerve in diabetic rats after the up-regulation of Lipin1. The myelin sheath and axonal morphology were also observed in pathological observation.
【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類(lèi)號(hào)】：R587.2

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 唐勝球;江青艷;楊楚芬;鄒曉庭;董小英;;Lipin家族研究進(jìn)展[J];遺傳;2010年10期

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本文編號(hào)：2082754