糖皮质激素双向调节骨髓基质干细胞的分化机制

骨质疏松症是以骨量减少、骨显微结构退化为特征,以致骨脆性增高及骨折危险性增加的一种全身性疾病。糖皮质激素（ GC）因其具有非常好的抗炎和免疫调节作用而被临床上广泛使用,而过量的使用糖皮质激素会导致骨质疏松症,称为糖皮质激素性骨质疏松症,属于继发性骨质疏松症。骨髓基质干细胞（ BMSCs）具有多向分化潜能,能够分化为成骨细胞和脂肪细胞,两者相互竞争,此消彼长。糖皮质激素在正常范围内可促进BMSCs向成骨或成脂方向分化,而在这一过程中,多种调控因子可与其联合作用,促进或抑制BMSCs的成骨分化。本文就糖皮质激素对BMSCs的双向调节机制作一综述,阐述各因素与糖皮质激素的联合协同作用,从成骨最大化的角度探讨激素性骨质疏松的防治方法。     

间充质干细胞治疗胰腺炎的研究进展

目前胰腺炎的临床治疗仍以对症支持治疗为主,具有住院周期长、医疗费用高和高病死率,因此亟需寻找到一种新的治疗策略。间充质干细胞(MSCs)因其高度的自我更新、多向分化潜能、低免疫原性以及免疫调节功能等优势,已成为再生医学中组织或器官修复的理想种子细胞。近年来众多研究发现MSCs移植胰腺炎动物模型后,不但可归巢到损伤区域,而且可通过抗炎、抗凋亡、促血管新生及免疫调节作用等促进胰腺组织的修复,这表明MSCs有望成为治疗胰腺炎的新策略。笔者就MSCs在急、慢性胰腺炎治疗中的最新研究进展作一综述。     

胆碱能抗炎通路研究进展及其在中医药研究中的应用

胆碱能抗炎通路（CAP）是一条以迷走神经、乙酰胆碱及特异性乙酰胆碱受体为基础的神经-免疫调节通路，与传统抗炎机制相比较，CAP抗炎作用更加快速、 有效，并具有特异性。研究证实，中医药能够作用于CAP发挥抗炎作用。现就CAP的定义、抗炎机制以及中医药对CAP的影响进行综述。     

血管内皮生长因子信号系统与急性肺损伤研究进展

血管内皮生长因子(vascular endothelial growth factor,VEGF)作为一种多功能的细胞生长因子,能够增加血管通透性进而加剧炎性反应,也能够促进血管内皮细胞有丝分裂、增殖、存活,从而诱导血管生成,促进组织修复等。VEGF信号系统在急性肺损伤(acute lung injury,ALI)中的作用目前仍存在较大争议。文章就VEGF信号系统在ALI发生、发展过程中的变化和作用进行综述,这对深入了解ALI的发病机制和病理过程,开发特效药物和治疗手段提供新的途径,从而使迅速有效预防和治疗ALI、减少病死率、改善患者预后成为可能。     

右旋美托咪啶对肺损伤的保护作用及机制

背景 严重感染、休克等多种因素将导致急性肺损伤(acute lung injury,ALI),肺损伤的原因考虑与肺内过度、失控的炎症反应有关,肺损伤的发生会增加患者并发症的发生率及病死率,影响患者预后.右旋美托咪啶(dexmedetomidine,DEX)除具有镇静、镇痛作用外,多个研究证实还具有独特的抗炎及脏器保护作用. 目的 综述DEX对肺损伤的保护作用及其机制. 内容 DEX的药理特点,肺损伤的发病机制,DEX对肺损伤的保护作用及其机制. 趋向 DEX具有明显的肺损伤保护作用,但该作用主要在动物实验中发现,尚未见大规模临床研究证实,需进一步研究其临床疗效,扩展该药的临床应用范围.     

1-磷酸鞘氨醇在急性肺损伤中的作用研究进展

1-磷酸鞘氨醇（S1P）是磷脂代谢过程中的主要产物,具有促进细胞增殖、迁移、凋亡,维持血管内皮屏障功能等作用。最新研究显示,S1P能够减轻急性肺损伤（ALI）及其引起的炎症等,但在使用剂量上仍需斟酌。间充质干细胞（MSC）因具有自我复制、多向分化等特点,且在造血、免疫调控、组织修复方面具有优势,已成为新兴疗法,对ALI...     

多不饱和脂肪酸衍生物对急性肺损伤的保护作用研究进展

背景急性肺损伤（acute lung injury,ALI）是目前严重威胁人类健康的疾病之一。有大量研究表明：源自多不饱和脂肪酸（polyunsaturated fatty acids,PUFA）的一些特殊的促炎症消退介质（specialized pro-resolving mediators,SPM）对ALI具有一定的保护作用。目的分析总结SPM对ALI的保护作用和机制。内容此文描述SPM的分子生物学特征、炎症与ALI的关系,SPM的抗炎和促进炎症消退的保护作用及机制3个方面。趋向SPM对ALI具有一定的保护作用,这对于临床上治疗ALI提供了一种新的思路和方法。     

机械牵张导致肺上皮细胞损伤的信号转导机制研究进展

临床上机械通气导致急性肺损伤 (ALI)已成事实 ,但机械张力转化为生物学损伤 (biotrauma)的机制尚不清楚。现就近年来机械张力对离体肺上皮细胞的结构形态和功能改变以及细胞内炎性因子产生的上游信号转导可能机制作一综述。     

电针刺在急性肺损伤中的保护机制

背景 急性肺损伤(acute lung injury,ALI)发病率和病死率较高,治疗棘手,是临床常见的急危重症. 目的 阐述动物实验研究中电针刺对ALI的可能保护机制. 内容 电针刺对ALI的保护机制可能涉及维持氧化/抗氧化系统平衡、促炎/抗炎反应平衡、神经内分泌系统平衡,血管舒缩功能平衡及减轻缺血/再灌注损伤等. 趋向 导致ALI因素多样、机制复杂,电针刺激可能通过调节机体内源性保护系统从不同环节对受损伤肺脏起保护作用,且各环节之间相互联系.     

机械牵张导致肺上皮细胞损伤的信号转导机制研究进展

临床上机械通气导致急性肺损伤(ALI)已成事实，但机械张力转化为生物学损伤(biotmuma)的机制尚不清楚。现就近年来机械张力对离体肺上皮细胞的结构形态和功能改变以及细胞内炎性因子产生的上游信号转导可能机制作一综述。     

一氧化氮和一氧化氮合成酶在急性肺损伤的作用

急性肺损伤(acute lung injury,ALI)是一种发病率和死亡率都很高的常见临床疾病. 目前,对ALI病理生理学基础和临床研究方面的了解越来越多,但并没有提出新的治疗策略能够明显改善ALI的治疗.在ALI的动物模型和患者中,一氧化氮合成酶(nitric oxide synthases,NOS)表达及活性增强和一氧化氮(NO)的增多在ALI的病理生理过程中有重要作用;但临床抑制NO生成以及选择性抑制NOS并没有对ALI的治疗有明显效果.目前提出了不同细胞源性NO的概念,这种NO的细胞源性差异可能对ALI的治疗有潜在的意义.现综述NO和NOS在ALI中的作用.     

What tidal volumes should be used in patients without acute lung injury?

Mechanical ventilation practice has changed over the past few decades, with tidal volumes (VT) decreasing significantly, especially in patients with acute lung injury (ALI). Patients without acute lung injury are still ventilated with large--and perhaps too large--VT. Studies of ventilator-associated lung injury in subjects without ALI demonstrate inconsistent results. Retrospective clinical studies, however, suggest that the use of large VT favors the development of lung injury in these patients. Side effects associated with the use of lower VT in patients with ALI seem to be minimal. Assuming that this will be the case in patients without ALI/acute respiratory distress syndrome too, the authors suggest that the use of lower VT should be considered in all mechanically ventilated patients whether they have ALI or not. Prospective studies should be performed to evaluate optimal ventilator management strategies for patients without ALI.     

Pharmacogenetic treatment of acute respiratory distress syndrome

Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) occur due to systemic inflammatory disorders or direct injury to the lung. The occurrence of ALI/ARDS is sporadic and is not reliably predicted by the type or severity of injury. A combination of patient characteristics and mechanism of injury are responsible for the sporadic nature of ALI/ARDS and its observed phenotypic variability. Research on the pathophysiology and genetics of ALI/ARDS continues to advance, revealing critical molecular pathways in disease development and specific genetic factors that alter the expression of disease. Despite these advances, pharmacologic therapies have yet to be developed for the prevention or treatment of disease. We anticipate that continued improvement of our understanding of the genetic and pathophysiologic mechanisms underlying ALI/ARDS combined with future clinical trials will allow pharmacogenetic therapies for ALI/ARDS to be developed.     

Low vs high positive end-expiratory pressure in the ventilatory management of acute lung injury

Positive end-expiratory pressure (PEEP) has become an essential component of the care of many critically ill patients who require ventilatory support. The application of PEEP is expected to improve lung mechanics and gas exchange as it recruits lung volume. In the last 3 decades, research of the effects of PEEP in animal models of lung injury and in patients with acute respiratory failure has produced a plethora of information. Support for the use of PEEP comes from historical comparisons and a few randomized controlled studies. Although the data from those animal studies and clinical trials could be seen as very convincing, there are insufficient data to propose an universal approach for the use of PEEP in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). In this article I will review the basic mechanisms of PEEP and the current knowledge of the effects of PEEP on the evolution and outcome of ALI/ARDS.     

Acute lung injury and acute respiratory distress syndrome--what should we know?

Acutelunginjury (ALI) and its more severe form acute respiratory distress syndrome (ARDS) are syndromes with a spectrum of increasing severity of lung injury defined by physiologic and radiographic criteria. There are many clinical disorders as sociated with the development of ALI/ARDS and can be divided into those associated with direct or indirect lung injury. Early detection and protective lung ventilation strategy contribute to lowering the mortality rate.     

重症胰腺炎合并肺损伤36例临床治疗体会

目的 探讨重症胰腺炎合并肺损伤的治疗方法.方法 回顾性分析我院2002年1月～2006年1月收治的重症胰腺炎36例的临床资料.结果 本组病人均合并有不同程度的呼吸功能障碍.其中,急性肺损伤29例,急性呼吸窘迫综合征7例.治愈35例,死亡1例.结论 急性肺损伤和/或急性呼吸窘迫综合征是重症胰腺炎病人较早发生的严重并发症.严密监测、及时治疗可改善其预后.     

Vascular endothelial growth factor (VEGF) in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS): paradox or paradigm?

Acute respiratory distress syndrome (ARDS), the most severe form of acute lung injury (ALI), remains a devastating condition with a high mortality. It is characterised by alveolar injury and increased pulmonary vascular permeability. Vascular endothelial cell growth factor (VEGF) was identified by its properties to increase permeability and act as a cellular growth factor, hence its potential for a key role in the pathogenesis of ALI/ARDS. This review describes the basic biology of VEGF and its receptors as an essential prerequisite to discussing the available and sometimes paradoxical published data, before considering a paradigm for the role of VEGF in the human lung.     

Effects of hypercapnia and hypercapnic acidosis on attenuation of ventilator-associated lung injury

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are associated with impaired gas exchange, severe inflammation and alveolar damage including cell death. Patients with ALI or ARDS typically experience respiratory failure and thus require mechanical ventilation for support, which itself can aggravate lung injury. Recent developments in this field have revealed several therapeutic strategies that improve gas exchange, increase survival and minimize the deleterious effects of mechanical ventilation. Among those strategies is the reduction in tidal volume and allowing hypercapnia to develop during ventilation, or actively inducing hypercapnia. Here, we provide an overview of hypercapnia and the hypercapnic acidosis that typically follows, as well as the therapeutic effects of hypercapnia and acidosis in clinical studies and experimental models of ALI. Specifically, we review the effects of hypercapnia and acidosis on the attenuation of pulmonary inflammation, reduction of apoptosis in alveolar epithelial cells, improvement in sepsis-induced ALI and the therapeutic effects on other organ systems, as well as the potentially harmful effects of these strategies. The clinical implications of hypercapnia and hypercapnic acidosis are still not entirely clear. However, future research should focus on the intracellular signaling pathways that mediate ALI development, potentially focusing on the role of reactive biological species in ALI pathogenesis. Future research can also elucidate how such pathways may be targeted by hypercapnia and hypercapnic acidosis to attenuate lung injury.     

Risk factors for acute lung injury after thoracic surgery for lung cancer

Acute lung injury (ALI) may complicate thoracic surgery and is a major contributor to postoperative mortality. We analyzed risk factors for ALI in a cohort of 879 consecutive patients who underwent pulmonary resections for non-small cell lung carcinoma. Clinical, anesthetic, surgical, radiological, biochemical, and histopathologic data were prospectively collected. The total incidence of ALI was 4.2% (n = 37). In 10 cases, intercurrent complications (bronchopneumonia, n = 5; bronchopulmonary fistula, n = 2; gastric aspiration, n = 2; thromboembolism, n = 1) triggered the onset of ALI 3 to 12 days after surgery, and this was associated with a 60% mortality rate (secondary ALI). In the remaining 27 patients, no clinical adverse event preceded the development of ALI-0 to 3 days after surgery-that was associated with a 26% mortality rate (primary ALI). Four independent risk factors for primary ALI were identified: high intraoperative ventilatory pressure index (odds ratio, 3.5; 95% confidence interval, 1.7-8.4), excessive fluid infusion (odds ratio, 2.9; 95% confidence interval, 1.9-7.4), pneumonectomy (odds ratio, 2.8; 95% confidence interval, 1.4-6.3), and preoperative alcohol abuse (odds ratio, 1.9; 95% confidence interval, 1.1-4.6). In conclusion, we describe two clinical forms of post-thoracotomy ALI: 1). delayed-onset ALI triggered by intercurrent complications and 2). an early form of ALI amenable to risk-reducing strategies, including preoperative alcohol abstinence, lung-protective ventilatory modes, and limited fluid intake. IMPLICATIONS: In an observational study including all patients undergoing lung surgery, we describe two clinical forms of acute lung injury (ALI): a delayed-onset form triggered by intercurrent complications and an early form associated with preoperative alcohol consumption, pneumonectomy, high intraoperative pressure index, and excessive fluid intake over the first 24 h.