CCK-8對LPS誘導(dǎo)ECV-304 iNOS表達(dá)的調(diào)節(jié)作用及其信號轉(zhuǎn)導(dǎo)機制的研究
發(fā)布時間：2018-11-11 11:19
【摘要】： 內(nèi)毒素休克是臨床常見的休克類型之一,死亡率極高,一直是醫(yī)學(xué)研究的重點課題。內(nèi)毒素休克的主要發(fā)生原因是嚴(yán)重的外源性感染、中毒;在法醫(yī)學(xué)實踐中,嚴(yán)重創(chuàng)傷、失血失液及嚴(yán)重應(yīng)激可引起體循環(huán)血壓下降或體內(nèi)血液再分布,致使腸粘膜缺血及局部免疫功能紊亂、腸粘膜屏障功能破壞,腸源性內(nèi)毒素脂多糖(lipopolysaccharide,LPS)入血,造成腸源性內(nèi)毒素血癥,也是內(nèi)毒素休克發(fā)生的常見原因。 血管調(diào)節(jié)機制紊亂是內(nèi)毒素休克特征性病理改變之一,主要表現(xiàn)為內(nèi)毒素休克發(fā)生早期主動脈壓下降、肺動脈壓升高以及離體肺動脈及主動脈血管反應(yīng)異常變化。研究發(fā)現(xiàn),血管內(nèi)皮細(xì)胞(vascular endothelial cells, VEC)能合成多種血管活性物質(zhì),是維持血管正常張力狀態(tài)和血管反應(yīng)性的關(guān)鍵因素。其中VEC釋放的一氧化氮(nitric oxide,NO)是人們發(fā)現(xiàn)的機體第一種氣體信使分子,具有明顯的血管活性、介導(dǎo)了血管內(nèi)皮依賴性舒張反應(yīng)。在內(nèi)毒素休克過程中VEC是LPS及其誘導(dǎo)機體產(chǎn)生的多種促炎細(xì)胞因子如TNF、IL-1作用的主要靶細(xì)胞,VEC誘導(dǎo)型一氧化氮合酶(inducible nitric oxide synthase, iNOS)激活、NO大量誘生而內(nèi)皮型一氧化氮合酶(endothelial nitric oxide synthase, eNOS)活性被抑制、NO生成障礙,是血管反應(yīng)性異常變化、血管調(diào)節(jié)機制紊亂的重要發(fā)病環(huán)節(jié)。適當(dāng)調(diào)控VEC NO生成有助于緩解內(nèi)毒素休克血管調(diào)節(jié)機制紊亂、減輕血液動力學(xué)異常變化,成為防治內(nèi)毒素休克的重要途徑。 八肽膽囊收縮素(cholecystokinin octapeptide, CCK-8)是一種十分重要的神經(jīng)調(diào)節(jié)肽,具有明確的抗內(nèi)毒素休克作用。用CCK-8預(yù)處理內(nèi)毒素休克大鼠可使降低的平均動脈壓回升而增高的肺動脈壓降低,提高離體肺動脈、胸主動脈的血管內(nèi)皮依賴性舒張反應(yīng),改善胸主動脈對縮血管劑反應(yīng)性降低,表明CCK-8的抗內(nèi)毒素休克效應(yīng)存在著外周血管機制,與調(diào)控VEC NO生成有關(guān)。然而CCK-8抗休克作用的分子機制,特別是調(diào)控VEC NO生成的分子機制尚未完全闡明,有待于進一步探討。本課題
[Abstract]:Endotoxin shock is one of the most common shock types in clinic, and the death rate is very high. The main cause of endotoxic shock is severe exogenous infection and poisoning. In the practice of forensic medicine, severe trauma, loss of blood and severe stress can cause the decrease of blood pressure of systemic circulation or the redistribution of blood in the body, resulting in intestinal mucosal ischemia and disturbance of local immune function, and the destruction of intestinal mucosal barrier function. Intestinal endotoxin lipopolysaccharide (lipopolysaccharide,LPS) is a common cause of endotoxemia. The disturbance of vascular regulation mechanism is one of the characteristic pathological changes of endotoxic shock. The main manifestations are the decrease of aortic pressure in early stage of endotoxic shock, the increase of pulmonary artery pressure and the abnormal changes of vascular reaction in isolated pulmonary artery and aorta. It has been found that vascular endothelial cells (vascular endothelial cells, VEC) can synthesize many vasoactive substances, which is the key factor to maintain the normal tension state and vascular reactivity of vascular. Nitric oxide (nitric oxide,NO) released by VEC is the first gas messenger molecule which has obvious vascular activity and mediates endothelium-dependent vasodilation. During endotoxic shock, VEC is the main target cell of LPS and many proinflammatory cytokines such as TNF,IL-1, and VEC inducible nitric oxide synthase (inducible nitric oxide synthase, iNOS) is activated. The activity of endothelial nitric oxide synthase (endothelial nitric oxide synthase, eNOS) is inhibited and the production of NO is impaired by NO, which is an important part of vascular reactivity and vascular regulation disorder. The proper regulation of VEC NO production is helpful to alleviate the disorder of vascular regulation mechanism in endotoxic shock and to alleviate the abnormal changes of hemodynamics, which is an important way to prevent and treat endotoxic shock. Cholecystokinin octapeptide (cholecystokinin octapeptide, CCK-8) is a very important neuroregulatory peptide and has a definite anti-endotoxic effect. Pretreatment with CCK-8 in endotoxic shock rats could increase the mean arterial pressure and increase the pulmonary artery pressure, and increase the endothelium-dependent relaxation response of isolated pulmonary artery and thoracic aorta. The reduction of aortic reactivity to vasoconstrictor indicated that the antiendotoxic shock effect of CCK-8 has a peripheral vascular mechanism, which is related to the regulation of VEC NO production. However, the molecular mechanism of CCK-8 antishock, especially the molecular mechanism of regulating VEC NO production, has not been fully clarified, which needs further study. This subject
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2006
【分類號】：D919
[Abstract]:Endotoxin shock is one of the most common shock types in clinic, and the death rate is very high. The main cause of endotoxic shock is severe exogenous infection and poisoning. In the practice of forensic medicine, severe trauma, loss of blood and severe stress can cause the decrease of blood pressure of systemic circulation or the redistribution of blood in the body, resulting in intestinal mucosal ischemia and disturbance of local immune function, and the destruction of intestinal mucosal barrier function. Intestinal endotoxin lipopolysaccharide (lipopolysaccharide,LPS) is a common cause of endotoxemia. The disturbance of vascular regulation mechanism is one of the characteristic pathological changes of endotoxic shock. The main manifestations are the decrease of aortic pressure in early stage of endotoxic shock, the increase of pulmonary artery pressure and the abnormal changes of vascular reaction in isolated pulmonary artery and aorta. It has been found that vascular endothelial cells (vascular endothelial cells, VEC) can synthesize many vasoactive substances, which is the key factor to maintain the normal tension state and vascular reactivity of vascular. Nitric oxide (nitric oxide,NO) released by VEC is the first gas messenger molecule which has obvious vascular activity and mediates endothelium-dependent vasodilation. During endotoxic shock, VEC is the main target cell of LPS and many proinflammatory cytokines such as TNF,IL-1, and VEC inducible nitric oxide synthase (inducible nitric oxide synthase, iNOS) is activated. The activity of endothelial nitric oxide synthase (endothelial nitric oxide synthase, eNOS) is inhibited and the production of NO is impaired by NO, which is an important part of vascular reactivity and vascular regulation disorder. The proper regulation of VEC NO production is helpful to alleviate the disorder of vascular regulation mechanism in endotoxic shock and to alleviate the abnormal changes of hemodynamics, which is an important way to prevent and treat endotoxic shock. Cholecystokinin octapeptide (cholecystokinin octapeptide, CCK-8) is a very important neuroregulatory peptide and has a definite anti-endotoxic effect. Pretreatment with CCK-8 in endotoxic shock rats could increase the mean arterial pressure and increase the pulmonary artery pressure, and increase the endothelium-dependent relaxation response of isolated pulmonary artery and thoracic aorta. The reduction of aortic reactivity to vasoconstrictor indicated that the antiendotoxic shock effect of CCK-8 has a peripheral vascular mechanism, which is related to the regulation of VEC NO production. However, the molecular mechanism of CCK-8 antishock, especially the molecular mechanism of regulating VEC NO production, has not been fully clarified, which needs further study. This subject
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2006
【分類號】：D919
【參考文獻】
相關(guān)期刊論文 前10條
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