ATRA对AS兔动脉血管内皮依赖性舒张功能的影响及其机制的探讨

发布时间：2018-04-19 13:33

本文选题：动脉粥样硬化 + ATRA　；参考：《安徽医科大学》2017年硕士论文

【摘要】：目的探讨全反式维甲酸(all-trans-retinoic acid,ATRA)对实验性动脉粥样硬化兔动脉血管内皮舒张功能的影响及其机制。方法普通级新西兰大耳白兔随机分3组,正常组:饲喂普通饲料;模型组:饲喂高脂饲料(普通饲料+1%胆固醇+5%猪油);ATRA组:饲喂高脂饲料,同时ATRA灌胃5 mg/(kg·d)。8周后,麻醉处死,颈动脉取血,检测血脂浓度。动脉大体油红染色观察斑块形成情况。HE染色观察动脉内皮结构变化。高分辨率血管超声检测内皮舒张功能。离体动脉环实验检测ATRA对动脉内皮舒张功能的影响。免疫组织化学实验检测MLCK在动脉血管的表达情况。Western blot检测动脉MLCK及MAPK信号通路相关蛋白的表达情况。结果高脂饮食8周后,模型组动脉粥样硬化形成,ATRA灌胃后,对动脉粥样硬化的发生有抑制作用。与正常组相比,模型组血清中三酰甘油(TG)、总胆固醇(TCH)、高密度脂蛋白-胆固醇(HDL-c)、低密度脂蛋白-胆固醇(LDL-c)浓度明显升高(P0.05);油红染色表明脂质斑块明显;HE染色显示血管内膜增厚,泡沫细胞增多,平滑肌细胞极性紊乱,向内膜迁移;离体动脉环实验和高分辨率血管超声实验表明内皮依赖性舒张功能显著低于正常组(P0.05);MLCK及MAPK信号通路相关蛋白(P38,JNK,ERK)表达水平显著升高(P0.05)。与模型组相比,ATRA组血清中TG,HDL-c,LDL-c浓度无差异,TCH浓度显著降低(P0.05);油红染色可见脂质斑块;HE染色可见血管内膜稍微增厚,泡沫细胞减少,平滑肌细胞排列较整齐;内皮依赖性舒张功能明显提高(P0.05);MLCK及MAPK信号通路相关蛋白(P38,JNK,ERK)表达水平显著下降(P0.05)结论高脂饮食可使动脉粥样硬化发生,动脉内皮损伤,动脉内皮损伤使血管内皮舒张功能下降,ATRA可降低血清中总胆固醇浓度。ATRA改善动脉粥样硬化内皮依赖性舒张功能,其机制可能与MAPK信号通路抑制动脉MLCK的表达有关。
[Abstract]:Objective to investigate the effect of all-trans-retinoic acid ATRAA on endothelium diastolic function and its mechanism in experimental atherosclerotic rabbits.Methods New Zealand white rabbits were randomly divided into three groups: normal group: normal group: fed normal diet, model group: fed high fat diet (1% cholesterol 5% lard) group: fed high fat diet, and ATRA was fed intragastric for 5 mg/(kg for 8 weeks.Blood was taken from carotid artery and blood lipid concentration was measured.Arterial gross oil red staining was used to observe the plaque formation. He staining was used to observe the changes of arterial endothelial structure.Endothelial diastolic function was measured by high resolution ultrasound.The effect of ATRA on endothelium diastolic function was detected by isolated arterial ring experiment.Immunohistochemistry was used to detect the expression of MLCK in arterial vessels. Western blot was used to detect the expression of MLCK and MAPK signal transduction related proteins.Results after 8 weeks of high fat diet, the formation of atherosclerosis in model group was inhibited by ATRA.Compared with the normal group, the serum levels of TGG, TCHG, HDL-cC, LDL-cc in the model group were significantly higher than those in the normal group, and the oil red staining showed that the lipid plaque was obviously stained with HE to show the thickening of the vascular intima.Foam cells increased, smooth muscle cells polarity disorder, migration to the intima;The results of isolated arterial ring test and high resolution vascular ultrasound showed that the endothelium-dependent diastolic function was significantly lower than that in the normal control group (P 0.05 MLCK and MAPK signal pathway related protein P38 JNKN ERK) expression was significantly higher than that in the control group (P 0.05).Compared with the model group, there was no significant difference in serum TGN HDL-cU LDL-c concentration between the ATRA group and the model group. The concentration of tch decreased significantly in the serum of ATRA group, and the lipid plaque was stained with oil red, the intima was slightly thicker, the foam cells were decreased, and the smooth muscle cells were arranged neatly.Endothelium-dependent diastolic function significantly increased the expression of P0.05MLCK and MAPK signaling pathway related protein P38-JNK-ERK (P 0.05). Conclusion High fat diet can induce atherosclerosis and injury of arterial endothelium.Vascular endothelial diastolic function decreased after arterial endothelial injury. ATRA could decrease serum total cholesterol concentration. ATRA could improve endothelium-dependent diastolic function of atherosclerotic rats. The mechanism may be related to the inhibition of MLCK expression by MAPK signaling pathway.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R543.5

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