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一氧化碳釋放分子-2對實驗性牙周炎大鼠動脈粥樣硬化的作用

發(fā)布時間:2019-06-21 00:06
【摘要】:研究目的: 牙周炎是一種細菌感染為主多種因素共同作用下的慢性感染性疾病,其發(fā)生發(fā)展與全身多種疾病有著密切的關(guān)系。近年來牙周炎與動脈粥樣硬化的關(guān)系受到日益關(guān)注,其中,牙周致病菌誘發(fā)的免疫炎性反應(yīng)是牙周炎與動脈粥樣硬化具有相關(guān)性的生物學(xué)基礎(chǔ),血清C反應(yīng)蛋白(C react protein,CRP)、可溶性血管細胞黏附分子1(soluble vascular cell adhesion molecule-1,sVCAM-1)及氧化型低密度脂蛋白(oxidized low density lipoprotein,ox-LDL)的水平已被發(fā)現(xiàn)與動脈粥樣硬化的發(fā)生發(fā)展呈正相關(guān)。一氧化碳釋放分子(CORM)是近年來合成的一種化合物,具有抗炎、調(diào)節(jié)白細胞粘附、舒張血管及抗血管內(nèi)皮細胞凋亡等多種作用。在本研究中,我們以實驗性牙周炎大鼠為動物實驗?zāi)P?擬研究CORM對牙周炎大鼠血清中動脈粥樣硬化相關(guān)指標的調(diào)節(jié)作用,初步探討CORM對牙周炎個體動脈粥樣硬化形成的影響,以期為牙周炎及其相關(guān)動脈粥樣硬化癥的治療提供實驗基礎(chǔ)和理論依據(jù)。 研究方法: 1.動物的選擇及分組:選擇雄性6周齡wistar大鼠40只(200±20g)。隨機分組分為正常組、牙周炎組(CP組)、一氧化碳干預(yù)組(CORM組)以及DMSO作用組。其中,CP組和CORM組采用絲線結(jié)扎同時局部注射內(nèi)毒素法建立牙周炎模型。CP組和CORM組自結(jié)扎當天起分別注射等體積無菌生理鹽水和一氧化碳釋放分子-2(CORM-2,10mg/kg/d),DMSO組同天起注射等體積DMSO+生理鹽水。注射時間連續(xù)4周。 2.實驗室檢測:分別于結(jié)扎后第1d、3d、7d、14d及28d,經(jīng)大鼠頸靜脈采血,ELISA方法檢測血清中CRP,sVCAM-1,ox-LDL及IL-10含量。28d后取大鼠降主動脈進行油紅O染色,觀察各組脂質(zhì)沉積情況。 3.統(tǒng)計學(xué)分析:采用SPSS17.0統(tǒng)計軟件進行檢驗,以P0.05為差異有統(tǒng)計學(xué)意義。 結(jié)果: 1.對牙周炎炎癥的抑制作用 (1)臨床觀察結(jié)果: CORM組及CP組大鼠的第二磨牙在結(jié)扎絲線后牙頸部有菌斑堆積;一周后,牙齦紅腫且探診出血,可探及牙周袋;14天后CP組和CORM組大鼠中分別有80%及10%個體的第二磨牙松動度達Ⅱ~Ⅲ度。 (2)大體標本觀測結(jié)果:建模大鼠在4周后牙槽骨出現(xiàn)不同程度的吸收,CP組牙槽骨吸收量為2.47±0.31mm,高于CORM組2.05±0.22mm的牙槽骨吸收量(P0.05)。 (3)組織學(xué)觀察:正常組及DMSO組中牙周組織完整,幾乎無炎性細胞浸潤。而CORM組及CP組中牙周組織內(nèi)炎細胞浸潤程度為2的分別占25%和85%。 2.血清學(xué)檢驗結(jié)果 (1)CRP,ox-LDL及sVCAM-1水平檢驗結(jié)果:建模第3天始,CP組大鼠的CRP和sVCAM-1水平出現(xiàn)較持續(xù)性的增強,顯著高于CORM組(P0.05)。CORM組的ox-LDL水平在建模后第一天顯著高于正常組和DMSO組(P0.05),但顯著低于CP組(P0.05)。14天后,CP組的ox-LDL仍維持在高水平,但CORM組含量降至與正常組和DMSO組相近水平。 (2)IL-10水平檢驗結(jié)果:CORM組大鼠血清中IL-10水平在前7天內(nèi)穩(wěn)定上升并達到峰值,隨后逐漸下降,但含量明顯高于其他各組。(P0.05) 3.血管脂質(zhì)沉積結(jié)果 CP組中60%的大鼠動脈內(nèi)膜可見橙紅色脂質(zhì)染色,CORM組及其他兩組中均未發(fā)現(xiàn)脂質(zhì)沉積。 結(jié)論: 1.CORM-2在抑制實驗性大鼠牙周炎中牙周組織的炎癥反應(yīng)及牙槽骨吸收量的同時,降低了實驗性大鼠牙周炎模型中動脈粥樣硬化相關(guān)分子的水平,并顯著提高抗炎因子IL-10的表達,從而降低了大鼠降主動脈的脂質(zhì)沉積,對動脈粥樣硬化在牙周炎大鼠中的發(fā)生發(fā)展有一定的影響。 2.CORM-2在抑制實驗性牙周炎大鼠牙周炎性反應(yīng)的同時能夠?qū)用}粥樣硬化的發(fā)生發(fā)展有一定的抑制作用,為牙周病患者中動脈粥樣硬化的預(yù)防和治療提供了新的思路和方法。
[Abstract]:The purpose of the study: Periodontitis is a chronic infectious disease, which is a kind of bacterial infection, which is a kind of bacterial infection. The development of periodontitis is closely related to various diseases of the whole body. In recent years, the relationship between periodontitis and atherosclerosis is of increasing concern, among which, the inflammatory response induced by periodontal pathogens is the biological basis of the correlation between periodontitis and atherosclerosis, and the serum C-reactive protein (CRP) The levels of soluble vascular cell adhesion molecule 1 (sVCAM-1) and oxidized low density lipoprotein (ox-LDL) have been found to be normal to the development of atherosclerosis The carbon monoxide releasing molecule (CORM) is a compound synthesized in recent years. It has many functions such as anti-inflammation, regulating leukocyte adhesion, relaxing blood vessel and anti-vascular endothelial cell apoptosis. In this study, we used experimental periodontitis as animal experimental model to study the effect of CORM on the related indexes of atherosclerosis in the serum of periodontitis rats, and to study the effect of CORM on the formation of atherosclerosis in the patients with periodontitis. In order to provide experimental basis and theoretical basis for the treatment of periodontitis and its associated atherosclerosis. According to. Research Method:1. Selection and grouping of animals: selection of 40 male 6-week-old Wistar rats (200 (20 g). The randomization was divided into the normal group, the periodontitis group (CP group), the carbon monoxide intervention group (CORM group), and the DM. The group of SO action, in which the CP group and the CORM group were established by the local injection of endotoxin at the same time. Periodontitis model. The CP group and the CORM group were injected with equal volume of sterile saline and carbon monoxide releasing molecule-2 (CORM-2,10 mg/ kg/ day) from the day of ligation, and the DMSO group was injected with the same volume of DMSO as the day. + Saline. Injection 2. Laboratory test: The serum CRP, sVCAM-1, ox-LDL and IL-10 were detected by the method of blood collection and ELISA in the rat jugular vein after the ligation. Group lipid deposition.3. Statistical analysis: SPSS17.0 statistical software was used for the test, with the exception of P0.05. to be a difference There is a statistical significance. Results: 1. Inflammation of the periodontitis Inhibition (1) Clinical Observations: The second molar in the CORM group and the group of CP rats had a plaque build-up after the ligation of the silk thread; one week later In the 14-day CP group and in the CORM group,80% and 1 were found. The second molar loosening degree of 0% of the individual was up to the degree of 鈪,

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