發(fā)布時間：2018-06-28 11:03

  本文選題：慢性炎癥 + 配胖��； 參考：《南方醫(yī)科大學(xué)》2017年博士論文

【摘要】：1.研究背景及目的慢性炎癥是一系列慢性疾病,如肥胖、糖尿病等的共同病理機(jī)制。肥胖機(jī)體以長期的低度慢性系統(tǒng)性炎癥及免疫反應(yīng)異常、胰島素抵抗為重要特征,使其易感于重大代謝疾病包括糖尿病等。肥胖是糖尿病的重要病因,二者呈“孿生”流行趨勢,且均可促進(jìn)牙周炎的發(fā)展。而關(guān)于NLRP3信號通路在其中所起的關(guān)鍵作用的研究匱乏。本研究目的為探討肥胖及Ⅱ型糖尿病導(dǎo)致的系統(tǒng)性炎癥狀態(tài)對牙周組織炎癥的影響及NLRP3信號通路在其中所起的關(guān)鍵作用。2.研究方法(1)飲食誘導(dǎo)16周牙周結(jié)扎10天建立肥胖小鼠牙周炎模型,記為正常飲食組、正常飲食結(jié)扎組、高脂飲食組、高脂飲食結(jié)扎組。(2)體內(nèi)通過RT-PCR和IHC的方法檢測小鼠牙齦組織內(nèi)NLRP3信號通路(NLRP3,capase1,IL-1β,NFκb)及巨噬細(xì)胞表面標(biāo)記物F4/80、巨噬細(xì)胞趨化因子MCP1的表達(dá)情況。(3)體外分離培養(yǎng)不同飲食背景的小鼠BMDMs并對其進(jìn)行LPS刺激,通過RT-PCR及ICC檢測巨噬細(xì)胞內(nèi)NLRP3信號通路的表達(dá)。(4)收集人類健康組、慢性牙周炎組及慢性牙周炎伴Ⅱ型糖尿病組患者牙齦組織,體內(nèi)通過RT-PCR及IHC檢測牙齦組織內(nèi)NLRP3信號通路的表達(dá)。體外分離培養(yǎng)人牙齦上皮細(xì)胞并對其進(jìn)行高糖及LPS刺激實(shí)驗(yàn),通過RT-PCR及ICC檢測上皮細(xì)胞內(nèi)NLRP3信號通路的表達(dá)。3.研究結(jié)果(1)高脂飼料誘導(dǎo)16w小鼠的體重及血糖明顯高于正常飼料組。小鼠牙槽骨吸收:牙周炎組顯著高于非牙周炎組,高脂飲食組顯著高于正常飲食組。血清胰島素及炎癥因子TNF-α,IL-1β,IL-6,IL-10表達(dá)水平:高脂飲食組顯著高于正常飲食組。(2)小鼠牙齦組織中NLRP3,Caspasel,IL-1β及NFκb的mRNA及蛋白質(zhì)表達(dá)水平:牙周炎組顯著高于非牙周炎組。(3)小鼠牙齦組織中F4/80及MCP1的mRNA及蛋白質(zhì)表達(dá)水平:牙周炎組顯著高于非牙周炎組,高脂飲食組顯著低于正常飲食組。BMDMs中NLRP3信號通路因子的mRNA及蛋白質(zhì)表達(dá)水平:LPS刺激組顯著高于非刺激組,高脂飲食組顯著低于正常飲食組。(4)人牙齦組織中NLRP3信號通路因子的mRNA及蛋白質(zhì)表達(dá)水平:在伴有炎癥及Ⅱ型糖尿病的牙齦組織中表達(dá)顯著性升高。HGECs中NLRP3信號通路因子的mRNA及蛋白質(zhì)表達(dá)水平在高糖刺激后顯著升高。4.結(jié)論我們發(fā)現(xiàn),肥胖、Ⅱ型糖尿病的機(jī)體處于慢性炎癥狀態(tài)均加重了牙周炎的發(fā)生發(fā)展。肥胖導(dǎo)致感染的牙周組織內(nèi)巨噬細(xì)胞數(shù)量減少及活性降低,引起牙周固有免疫的異常,最終加重了牙周炎的局部炎癥狀況。而Ⅱ型糖尿病患者的高糖狀態(tài)可能通過牙齦上皮細(xì)胞NLRP3信號通路的高表達(dá)而加重慢性牙周炎的發(fā)生發(fā)展。
[Abstract]:1. Background and objective chronic inflammation is a common pathological mechanism of a series of chronic diseases such as obesity and diabetes. Obesity is characterized by chronic low degree chronic systemic inflammation, abnormal immune response and insulin resistance, which makes it susceptible to major metabolic diseases, including diabetes, etc. Obesity is an important cause of diabetes, both of which are "twin" epidemic trend, and can promote the development of periodontitis. However, there is little research on the key role of NLRP3 signaling pathway. The aim of this study was to investigate the effects of systemic inflammation induced by obesity and type 2 diabetes on periodontal inflammation and the key role of NLRP3 signaling pathway. Methods (1) Obesity mouse periodontitis model was established by 16 weeks periodontal ligation induced by diet for 10 days, which was recorded as normal diet group, normal diet ligation group, high fat diet group, and high fat diet group. High fat diet ligation group. (2) the expression of NLRP3 signal pathway (NLRP3 signal pathway), macrophage surface marker F4 / 80 and macrophage chemokine MCP1 in vitro were detected by RT-PCR and IHC in mice gingival tissue. (3) the expression of NLRP3 signal pathway (NLRP3) and macrophage surface marker F4 / 80, MCP1 were detected in vitro. Jing mice BMDMs were stimulated by LPS. The expression of NLRP3 signal pathway in macrophages was detected by RT-PCR and ICC. (4) gingival tissues were collected from healthy people, chronic periodontitis patients and chronic periodontitis patients with type 鈪，

本文編號：2077779