硫化氢抑制内质网应激改善大鼠主动脉血管钙化

发布时间：2018-01-14 08:39

本文关键词：硫化氢抑制内质网应激改善大鼠主动脉血管钙化　出处：《河北医科大学》2015年硕士论文　论文类型：学位论文

【摘要】：目的:证实硫化氢(hydrogen sulfide,H2S)通过抑制内质网应激(endoplasmic reticulum stress,ERS)改善血管钙化(vascular calcification,VC)。方法:维生素D3肌注和尼古丁灌胃(vitamin D3 plus nicotine,VDN)制备大鼠VC模型,动脉插管法测定血流动力学参数;取主动脉切片做HE染色;测定主动脉钙含量;测定主动脉和血浆碱性磷酸酶(alkaline phosphatase,ALP)活性;Western blot检测相关蛋白表达水平,包括主动脉平滑肌细胞收缩表型标志蛋白SM22α(smooth muscle 22α)和calponin-1,成骨样细胞表型标志蛋白RUNX2(runt-related transcription factor 2)和BMP2(bone morphogenetic protein 2),ERS标志蛋白CHOP(C/EBP-homologous protein),GRP78(glucose-regulated protein 78 k Da)和active-caspase12。结果:与对照组大鼠相比,VDN组大鼠主动脉钙含量、血浆和主动脉ALP活性和收缩压(systolic blood pressure,SBP)显著升高,主动脉组织SM22α和calponin-1表达水平显著降低,RUNX2和BMP2表达水平显著升高。而VDN大鼠腹腔给予Na HS(56μmol/kg)后可明显改善上述指标。此外,VDN组大鼠血管组织ERS相关蛋白CHOP,GRP78和active-caspase12的表达水平均显著上调,Na HS可显著抑制ERS相关蛋白的上调。ERS激动剂衣霉素(tunicamycin,TM)可抑制Na HS改善VC的作用,而ERS抑制剂4-苯丁酸(4-phenylbutyric acid,PBA)与Na HS具有相似的减轻VC的作用。结论:上述研究结果提示硫化氢具有改善VC的作用,其作用可能是通过抑制ERS途径实现的。上述结果为VC的预防与治疗提供了新的思路和靶点。
[Abstract]:Objective: to prove that hydrogen sulfide H2S) inhibits endoplasmic reticulum stress by inhibiting endoplasmic reticulum stress. ERS) to improve vascular calcification and vascular calcification. Methods: vitamin D _ 3 was injected intramuscularly and nicotine was administered intragastrically to make VC model of rats. Hemodynamic parameters were measured by arterial catheterization. The sections of aorta were stained with HE. The content of calcium in aorta was measured. The activity of alkaline phosphatase (ALP) in aorta and plasma was measured. The expression of related proteins was detected by Western blot. These include SM22 伪 smooth muscle 22 伪 and calponin-1. Osteoblast-like cell phenotypic marker proteins RUNX2(runt-related transcription factor 2 and BMP2 (. Bone morphogenetic protein 2). ERS marker protein (CHOP(C/EBP-homologous protein). GRP78(glucose-regulated protein 78 K Da) and active-caspase 12. Results: compared with control rats. In VDN group, aortic calcium content, plasma and aortic ALP activity and systolic blood pressure were significantly increased. The expression of SM22 伪 and calponin-1 in aorta was significantly decreased. The expression levels of RUNX2 and BMP2 were significantly increased, but Na HS(56 渭 mol / kg intraperitoneal administration of VDN rats could significantly improve the above indexes. In VDN group, the expression of ERS related protein CHOP-GRP78 and active-caspase12 were significantly up-regulated. NaHS significantly inhibited the upregulation of ERS related proteins. Ichlamycin I, the agonist of ERS, inhibited the effect of NaHS on the improvement of VC. ERS inhibitor 4-phenylbutyric acid. Conclusion: these results suggest that hydrogen sulfide can improve VC. These results provide new ideas and targets for the prevention and treatment of VC.
【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R543.1

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