本文關(guān)鍵詞：硫化氫抑制內(nèi)質(zhì)網(wǎng)應(yīng)激改善大鼠主動(dòng)脈血管鈣化　出處：《河北醫(yī)科大學(xué)》2015年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 硫化氫 血管鈣化 內(nèi)質(zhì)網(wǎng) 內(nèi)質(zhì)網(wǎng)應(yīng)激 血管平滑肌細(xì)胞

【摘要】：目的:證實(shí)硫化氫(hydrogen sulfide,H2S)通過抑制內(nèi)質(zhì)網(wǎng)應(yīng)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(dòng)脈插管法測定血流動(dòng)力學(xué)參數(shù);取主動(dòng)脈切片做HE染色;測定主動(dòng)脈鈣含量;測定主動(dòng)脈和血漿堿性磷酸酶(alkaline phosphatase,ALP)活性;Western blot檢測相關(guān)蛋白表達(dá)水平,包括主動(dòng)脈平滑肌細(xì)胞收縮表型標(biāo)志蛋白SM22α(smooth muscle 22α)和calponin-1,成骨樣細(xì)胞表型標(biāo)志蛋白R(shí)UNX2(runt-related transcription factor 2)和BMP2(bone morphogenetic protein 2),ERS標(biāo)志蛋白CHOP(C/EBP-homologous protein),GRP78(glucose-regulated protein 78 k Da)和active-caspase12。結(jié)果:與對(duì)照組大鼠相比,VDN組大鼠主動(dòng)脈鈣含量、血漿和主動(dòng)脈ALP活性和收縮壓(systolic blood pressure,SBP)顯著升高,主動(dòng)脈組織SM22α和calponin-1表達(dá)水平顯著降低,RUNX2和BMP2表達(dá)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(biāo)。此外,VDN組大鼠血管組織ERS相關(guān)蛋白CHOP,GRP78和active-caspase12的表達(dá)水平均顯著上調(diào),Na HS可顯著抑制ERS相關(guān)蛋白的上調(diào)。ERS激動(dòng)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(jié)論:上述研究結(jié)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(shí)現(xiàn)的。上述結(jié)果為VC的預(yù)防與治療提供了新的思路和靶點(diǎn)。
[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(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：R543.1

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本文編號(hào)：1422866