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  本文關鍵詞：硫化氫抑制內質網(wǎng)應激改善大鼠主動脈血管鈣化　出處：《河北醫(yī)科大學》2015年碩士論文　論文類型：學位論文

  更多相關文章： 硫化氫 血管鈣化 內質網(wǎng) 內質網(wǎng)應激 血管平滑肌細胞

【摘要】：目的:證實硫化氫(hydrogen sulfide,H2S)通過抑制內質網(wǎng)應激(endoplasmic reticulum stress,ERS)改善血管鈣化(vascular calcification,VC)。方法:維生素D3肌注和尼古丁灌胃(vitamin D3 plus nicotine,VDN)制備大鼠VC模型,動脈插管法測定血流動力學參數(shù);取主動脈切片做HE染色;測定主動脈鈣含量;測定主動脈和血漿堿性磷酸酶(alkaline phosphatase,ALP)活性;Western blot檢測相關蛋白表達水平,包括主動脈平滑肌細胞收縮表型標志蛋白SM22α(smooth muscle 22α)和calponin-1,成骨樣細胞表型標志蛋白RUNX2(runt-related transcription factor 2)和BMP2(bone morphogenetic protein 2),ERS標志蛋白CHOP(C/EBP-homologous protein),GRP78(glucose-regulated protein 78 k Da)和active-caspase12。結果:與對照組大鼠相比,VDN組大鼠主動脈鈣含量、血漿和主動脈ALP活性和收縮壓(systolic blood pressure,SBP)顯著升高,主動脈組織SM22α和calponin-1表達水平顯著降低,RUNX2和BMP2表達水平顯著升高。而VDN大鼠腹腔給予Na HS(56μmol/kg)后可明顯改善上述指標。此外,VDN組大鼠血管組織ERS相關蛋白CHOP,GRP78和active-caspase12的表達水平均顯著上調,Na HS可顯著抑制ERS相關蛋白的上調。ERS激動劑衣霉素(tunicamycin,TM)可抑制Na HS改善VC的作用,而ERS抑制劑4-苯丁酸(4-phenylbutyric acid,PBA)與Na HS具有相似的減輕VC的作用。結論:上述研究結果提示硫化氫具有改善VC的作用,其作用可能是通過抑制ERS途徑實現(xiàn)的。上述結果為VC的預防與治療提供了新的思路和靶點。
[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 偽 smooth muscle 22 偽 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 偽 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.
【學位授予單位】：河北醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：R543.1

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