【研究背景與目的】動脈粥樣硬化（atherosclerosis,As）是心腦血管疾病的主要病理基礎,近年來,由As所致的冠心病、腦卒中、心肌梗死等心腦血管疾病嚴重危害著人類的身心健康和生活質量,已成為嚴重的社會問題。研究表明,慢性應激已成為As性心血管疾病的重要獨立危險因素。因此,闡明慢性應激影響As病變的分子機制,對As的防治具有重要的意義。在本研究中,我們將探討高遷移率族蛋白B1（High mobility group box 1,HMGB1）/Toll樣受體4（Toll-like receptor 4,TLR4）途徑在慢性應激促進As病變中的作用及其機制。【方法】60只ApoE^-/-雄性小鼠隨機分為4組:對照組、慢性應激組、慢性應激+丙酮酸乙酯（HMGB1抑制劑）組、慢性應激+TAK242（TLR4抑制劑）組。首先,通過檢測血清皮質酮水平確定小鼠應激模型是否建立。采用Elisa和Western Blot,檢測慢性應激ApoE^-/-小鼠As模型血清中HMGB1的釋放含量和血管組織中HMGB1和TLR4的表達變化,以明確慢性應激對HMGB1... 

【文章來源】：南華大學湖南省

【文章頁數】：81 頁

【學位級別】：碩士

【部分圖文】：

EP或TAK242對CUMSApoE-/-小鼠血清皮質酮水平的影響

2 EP 或 TAK242 對 CUMSApoE-/-小鼠血清 HMGB1 水平 of EP and TAK-242 treatment on serum HMGB1 proteE-/-mice were injected with PBS, EP (50 mg/kg, once dailk) for consecutive 16 weeks by intraperitoneal injection 30 miriod treatment, blood samples were collected for assessment vels in serum were measured by ELISA. Data were expressedalysis was performed by One-Way analysis of variance. *P 0GB1/TLR4 途徑可減弱 CUMS 加重的 ApoEMS 促進 ApoE-/-小鼠 HMGB1 釋放的基礎上，我們隨性應激促進 ApoE-/-小鼠的 As 病變中作用及其機制劑 EP（50 mg/kg/d，腹腔注射）和 TLR4 抑制劑 TA-/--/-

圖 3.3 EP 或 TAK242 對 CUMSApoE-/-小鼠 As 病變的影響Figure 3.3 Effect of EP and TAK-242 treatment on atherosclerotic lesions in CUMS ApoE-/-mice.Male ApoE-/-mice were injected with PBS, EP (50 mg/kg, once daily), or TAK-242 (0.3 mg/kg, twicea week) for consecutive 16 weeks by intraperitoneal injection 30 minutes prior to CUMS. Over a16-week period treatment, entire aorta from the aortic root to the iliac bifurcation was harvested foranalysis of atherosclerotic lesions. (A) Representative images of H&E, ORO (Oil Red O, ORO), andMasson staining of aortic sinuses. (B) Quantification of atherosclerotic plaque areas of aortic sinusesrevealed that EP or TAK-242 treatment significantly decreased atherosclerotic lesions induced byCUMS (n = 15). (C) Quantification of collagen fibers content of aortic sinuses (n = 15). (D)Representative images of ORO staining of en face aortic atherosclerotic lesions. (E) Quantification ofatherosclerotic lesion areas of aorta was performed by using Image Pro Plus (n = 5). Data wereexpressed as mean ± S.E.M. Statistical analysis was performed by One-Way analysis of variance. *P 0.01, **P 0.01, ***P 0.001.


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