实验性动脉粥样斑块内泡沫细胞凋亡及葛根总黄酮的干预作用

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目的:观察ApoE基因敲除(ApoE gene knock out,ApoE-/-)小鼠主动脉窦动脉粥样硬化斑块超微结构改变,泡沫细胞凋亡,探讨葛根总黄酮(Total Flavone of Radix Puerariae,TFRP)的干预作用。方法:将16只Apo E-/-小鼠随机分为模型组及TFRP干预组(85 mg/kg.d),每组8只,2只C57BL/6J小鼠作为空白对照,12周后处死,用酶法检测二组血清脂质含量,采用光学显微镜、电子显微镜观察As斑块形态及泡沫细胞凋亡。结果:(1)两组血清总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)及高密度脂蛋白胆固醇(HDL-C)水平未见显著性差异;(2)光镜观察:模型组可见成熟的As斑块形成,部分斑块脂质核心较大,偏心性,纤维帽较薄,纤维帽内有较多炎症细胞浸润,平滑肌细胞成分少,肩部较薄弱,呈不稳定斑块形成趋势,在斑块脂质核心内可见到较多凋亡细胞;而TFRP干预组未见不稳定斑块,斑块脂质核心小,平滑肌细胞数目较多,纤维帽较厚,斑块内凋亡细胞数明显少于模型组(p<0.05)。(3)电镜观察:模型组斑块内以平滑肌源性泡沫细胞多见,可见中晚期凋亡细胞,细胞外基质成分较少;与模型组相比,TFRP干预组以巨噬细胞源性泡沫细胞多见,可见少数早期凋亡细胞,细胞外胶原纤维明显增多。结论:模型组病变处于中晚期As病变,符合泡沫细胞凋亡特征;TFRP干预抑制了ApoE基因敲除小鼠主动脉窦As斑块内泡沫细胞凋亡。 Objective: To observe the ultrastructural changes of atherosclerotic plaque in the aortic sinus apoplexy of ApoE gene knockout mice (ApoE-/-) and the apoptosis of foam cells. To investigate total flavonoids of total flavones in Pueraria lobata (Total Flavone of Radix Puerariae, TFRP) intervention. METHODS: Sixteen Apo E-/- mice were randomly divided into model group and TFRP intervention group (85 mg/kg.d), 8 mice in each group, 2 C57BL/6J mice as blank control, and sacrificed 12 weeks later. The serum lipid content of the two groups was detected by enzymatic method. The morphology of As plaque and foam cell apoptosis were observed by light microscope and electron microscope. Results: (1) There were no significant differences in serum total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels between the two groups; (2) Light microscopy: Models The formation of mature As plaques can be seen in the group. Some plaques have large lipid cores, eccentricity, thin fibrous caps, more inflammatory cell infiltrate in the fibrous cap, less smooth muscle cell components, weak shoulders, and unstable plaques. In the trend of block formation, more apoptotic cells were observed in the lipid core of the plaque; however, no unstable plaque was observed in the TFRP intervention group, the plaque lipid core was small, the number of smooth muscle cells was larger, the fibrous cap was thicker, and the plaque was The number of apoptotic cells was significantly lower than that of the model group (p<0.05). (3) Electron microscopic observation: In the model group, smooth muscle-derived foam cells were more common in the plaques, and the middle and late apoptotic cells were seen with less extracellular matrix components. Compared with the model group, the macrophage-derived foam was observed in the TFRP intervention group. Most of the cells were seen, and a few early apoptotic cells were seen, and extracellular collagen fibers were significantly increased. Conclusion: The lesions in the model group were in the late stage of As lesions, which was in line with the characteristics of foam cell apoptosis; TFRP intervention inhibited foam cell apoptosis in the aortic sinus As plaque in ApoE knockout mice.
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