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1.
骨质疏松症是世界常见病、多发病,医学界对骨质疏松症发病机理与防治的研究愈显重要。近年研究表明,各种原因导致的骨量减少常伴有骨髓中脂肪组织含量的增加。骨质疏松的发生可能与骨代谢中成脂和成骨的比例有关。骨髓中脂肪组织在骨形成和造血支持中发挥重要作用,脂肪组织具有内分泌调节功能,释放出一系列重要的分泌性因子,比如:leptin、adiponectin、chemerin、resistin、visfatin等,在调节骨髓间充质干细胞向脂肪细胞分化过程中起关键作用。chemerin是新发现的脂肪因子,它在免疫应答、脂质代谢、糖类代谢、炎症反应等生理病理过程中都起着重要的作用。它与leptin、adiponect等脂肪因子一样参与骨代谢的调节,对维持骨代谢的平衡起着重要的作用。chemerin及其受体CMKLR1信号传递通路的激活可以调节骨髓间充质干细胞的分化,促进破骨细胞的生成,从而影响影响骨的重建。现在chemerin/CMKLR1信号通路影响骨代谢的作用机制还不是很明确,深入研究chemerin及其受体与骨质疏松的关系,可以进一步了解骨质疏松症发生机制,为治疗及预防骨质疏松症及提供了新的方向。  相似文献   

2.
chemerin蛋白是一种分泌性的脂肪因子,其生理或病理功能的发挥要求与胞膜上CMKLR1、GPR1或CCRL2三种受体之一相结合,进而激发不同的下游分子事件或静默chemerin信号。chemerin/CMKLR1信号通路在免疫、脂肪生成、能量代谢以及维持骨量等生理进程中发挥作用。由于GPR1与CMKLR1在结构上具有较高的相似度,chemerin/GPR1信号通路也被证明具有类似的功能,目前对这两条信号通路的上下游分子调控机制也有一定的了解。但是,体外实验中chemerin结合CCRL2后,并未出现可检测到的下游信号激活。在骨质疏松的研究领域,对chemerin信号的研究主要集中于与受体CMKLR1结合后的分子事件及其调控。chemerin/CMKLR1信号通路可促进骨髓间充质干细胞(BMSC)成脂分化,抑制其成骨分化,并刺激造血干细胞(HSC)破骨分化,直接影响骨重塑过程,进而引起骨质疏松。干预该通路不仅可以从调控BMSC分化方向的角度刺激新骨形成,还可抑制非依赖成骨细胞的破骨细胞生成过程,减少骨吸收,因而具有治疗骨质疏松的潜力。  相似文献   

3.
骨髓间充质干细胞是存在于骨髓基质中的一种多能干细胞,具有多向分化的潜能,其天然再生能力对骨骼的生长代谢和骨转换起着至关重要的作用。Notch信号通路是一条在进化中高度保守的信号转导通路,与骨髓间充质干细胞的增殖、分化与凋亡密切相关,影响人体骨骼发育,也是多种骨代谢疾病的重要调节通路。以往对Notch信号通路的研究主要集中在神经干细胞,对骨髓间充质干细胞的研究较少。本文通过查阅文献,阐述不同的影响因素介导Notch信号通路对骨髓间充质干细胞分化的调节,并总结了Notch信号通路在骨代谢疾病如Alagille综合征、Adams Oliver综合征、脊椎肋骨发育不良、HajduCheney综合征、骨折愈合中的研究近况。  相似文献   

4.
骨质疏松症患者骨髓间充质干细胞(BMSCs)成骨分化能力减弱,成脂肪分化能力增强,脂肪组织增多,进而导致骨量 减少,可能是导致骨质疏松的原因之一。mioroRNA是一类起源于内源性转录物的单链非编码RNA,在BMSCs向脂肪细胞分 化及细胞发育成熟的过程中起重要的调控作用。本文通过检索有关BMSCs、mkroRNA、成脂肪细胞分化的相关文献并进行综 述,阐明了 mkroRNA通过调节Wnt、BMP和TGF-P信号通路上因子的表达来决定BMSCs向脂肪细胞分化,再通过调节 PPAR、C/EBP的表达来促使脂肪细胞成熟。因此,深人研究mkroRNA介导的BMSCs成脂肪细胞分化途径,将为我们深人了 解骨质疏松的发病机制具有重要意义。  相似文献   

5.
间充质干细胞成骨分化能力异常减弱和成骨细胞数量异常下降都会导致生物体内骨代谢紊乱,诱导骨质疏松症的发生。线粒体在MSC多能性保持和成骨分化过程中具有十分重要的作用,通过能量代谢、抗氧化途径、代谢相关信号通路、线粒体生物发生、线粒体动力学和线粒体自噬等参与间充质干细胞成骨分化的调控,形成了复杂的调节网络。本文综述了MSC成骨分化中线粒体的重要功能和作用,以及部分通过调节线粒体功能发挥抗骨质疏松治疗的药物,为进一步探讨间充质干细胞成骨分化功能失调的机制提供新的思路,为临床治疗骨质疏松症提供新的靶点。  相似文献   

6.
Hedgehog信号通路是一种高度保守而重要的信号通路,参与多种细胞的增殖和分化。骨质疏松症是一种常见的以骨量减少、骨组织微结构破坏为特征,导致骨质脆性增加和易于骨折的全身性骨代谢疾病,给社会造成了巨大的负担。骨质疏松症的发生发展受多种信号通路调控。近年来,国内外研究发现,Hedgehog通路是一个很有前途的参与骨形成和骨稳态的信号通路。已有研究证实,Hedgehog信号通路可能通过增加骨形成相关因子的表达,诱导骨髓间充质干细胞成骨分化,促进成骨细胞增殖分化,对防治骨质疏松症具有重要意义。本文综述了目前Hedgehog信号通路在骨形成调节中的作用机制及中医药的干预作用,旨在为促进骨形成、防治骨质疏松症提供新的作用靶点。  相似文献   

7.
骨质疏松症(Osteoporosis)是一种全身性的骨代谢障碍性疾病,以骨量减少,骨微结构退化,骨脆性增加,易发生骨折为特征的全身性疾病。随着社会逐渐进人老龄化,骨质疏松症也日趋成为影响健康的主要疾病,对骨质疏松治疗方面的研究就显得更加重要了。对骨质疏松症的更进一步研究发现骨髓间充质干细胞(BMSC)的衰老也是骨质疏松的发病机制之一。骨髓间充质干细胞(BMSC)是多能的干细胞,即能够自我更新并分化成多种细胞类型,包括脂肪细胞、成骨细胞、软骨细胞。 BMSC的植人能够有效增加局部骨量,提高骨密度,改善局部骨质疏松情况,可纠正骨代谢失衡,减少骨量丢失,增加成骨,为局部骨质疏松的治疗提供了一种新方法。  相似文献   

8.
骨质疏松症(osteoporosis,OP)是一种骨退行性慢性代谢性疾病,以骨量减少、骨组织微观结构退化,易骨折和骨的力学性能下降为特征。骨血管的生成、骨代谢中骨生成和骨吸收的平衡以及骨髓间充质干细胞的增殖、迁移和向成骨分化作用对于骨质疏松的发生发展及防治至关重要,氧是骨细胞生长、发育及功能代谢的重要条件,骨微环境处于天然的低氧状态下,其中维持骨稳态的成骨细胞和破骨细胞均属于氧感应细胞,缺氧诱导因子-1(hypoxia inducible factor-1,HIF-1)是具有转录活性的核蛋白,其活性亚基HIF-1α是细胞感知和适应氧调节机制的核心调控因子,在细胞氧调控中发挥着不可替代的作用,HIF-1α对骨血管生成以及骨代谢作用的研究为骨质疏松症的防治提供了更多可能。研究证明HIF-1α可通过多种信号通路、蛋白、miRNA等调节骨血管生成、成骨细胞和破骨细胞生成分化,调控骨髓间充质干细胞的增殖、迁移以及向成骨分化作用,HIF-1α可能成为防治骨质疏松症极具潜力的新靶点。本文旨在综述HIF-1α在骨血管生成及骨代谢方面对骨质疏松症发生发展的影响及防治作用。  相似文献   

9.
骨髓间充质干细胞作为多能干细胞的一种,在骨髓微环境中可主要分化为成骨细胞、脂肪细胞等,而这种成骨和成脂分化之间的相互制约和交互关系可被归纳为骨脂平衡,并且这种动态平衡对骨稳态的维持起着至关重要的作用。在骨脂交互作用的过程中,骨髓脂肪组织是沟通其信号的重要载体和关键途径,并介导着骨髓微环境中的多种代谢调控过程。近年来,随着研究人员对骨脂代谢方面研究的深入,其防治骨质疏松的相关调控网络逐渐得到揭示,但是目前对于在生理病理条件下骨脂分化状态及其分子机制仍缺少系统阐释。因此,本文拟通过总结相关文献并结合我们的研究,在明确骨髓微环境视野下骨脂平衡相关概念的基础上,深入剖析其分子机制,以便为骨质疏松症的防治提供新思路。  相似文献   

10.
现代社会肥胖人群逐年增多,肥胖相关代谢性骨病的患者也日益增多,严重危害人群健康。Chemerin作为一种脂肪因子,主要由脂肪细胞和肝细胞分泌,在循环中水平高于经典脂肪因子如Leptin和Adiponectin,对全身代谢和免疫发挥重要作用。近年研究发现,肥胖状态下伴随着外周脂肪组织的增多,骨髓内脂肪组织也急剧增加。骨髓内脂肪细胞分泌Chemerin,通过旁分泌或自分泌方式抑制成骨细胞分化和促进破骨细胞分化以及影响骨髓腔微环境。本文将系统回顾国内外有关Chemerin与骨代谢相关研究的文献,并探讨Chemerin对骨代谢的影响及其机制。  相似文献   

11.
Background : We investigated the vasopressor hormone response following mesenteric traction (MT) with hypotension due to prostacyclin (PGI2) release in patients undergoing abdominal surgery with a combined general and epidural anesthesia. Methods : In a prospective, randomized, placebo-controlled study we administered 400 mg ibuprofen (i.v.) in 42 patients scheduled for abdominal surgery. General anesthesia was combined with epidural anesthesia (T4-L1). Before as well as 5, 15, 30, 45, and 90 min after MT we recorded plasma osmolality, hemodynamics and measured 6-keto-PGFlα (stabile metabolite of PGI2), TXB2 (stabile metabolite of thromboxane A2) active renin, and arginine vasopressin (AVP) plasma concentrations by radioimmunoassay. Catecholamine levels were assessed by high-pressure liquid chromatography (HPLC) with electrochemical detection. Results : Following MT, arterial hypotension occurred along with a substantial PGI2 release. This was completely abolished by ibuprofen administration. Although plasma levels of 6-keto-PGF (1133 (708) vs. 60 (3) ng/L, median (median absolute deviation), P=0.0001, placebo vs. ibuprofen) remained significantly elevated, blood pressure was restored within 30 min after MT in the placebo group. At the same point in time plasma concentrations of TXB2 (164 (87) vs. 58 (1) ng/L, P=0.0001), epinephrine (46 (33) vs. 14 (6) ng/L, P=0.001), AVP (41 ± (18) vs. 12 (7) ng/L, P=0.0004), and active renin (27 (12) vs. 12 (4) ng/L, P = 0.001) were significantly higher in placebo-treated patients. Conclusion : Under combined general and epidural anesthesia arterial hypotension following MT due to endogenous PGI2 release is associated with enhanced release of AVP, active renin, epinephrine and thromboxane A2, presumably contributing to hemodynamic stability within 30 min after MT.  相似文献   

12.
Abstract: A variety of protein-bound or hydrophobic substances, accumulating as a result of pathologic conditions such as exogenous or endogenous intoxications, are removed poorly by conventional detoxification methods because of low accessibility (hemodialysis), insufficient adsorption capabilities (hemosorption), low efficiency (peritoneal dialysis), or economic limitations (high-volume plasmapheresis). Combining advantages of existing methods with microspheric technology, a module-based system was designed. Major operating parameters of the latter can be modified to allow for adjustment to individual clinical situations. An extracorporeal blood circuit including a plasmafilter is combined with a secondary high-velocity plasma circuit driven by a centrifugal pump. Different microspheric adsorbers can be combined in one circuit or applied in sequence. Thus, a prolonged treatment can be tailored using specially designed selective adsorber materials. Comparing this system with existing methods (high-flux hemodialysis, molecular adsorbent recycling system), results from our in vitro studies and animal experiments demonstrate the superior efficiency of substance removal.  相似文献   

13.
Background: Obesity is increasing globallly, including in the formerly "Eastern Bloc" countries. Methods: A survey was made of obesity and bariatric surgery. Results: In the 8 East and Central European countries studied, with total population 300 million, roughly 43% of the population was overweight (BMI 25-30), 23% obese (BMI > 30), with about 15 million people morbidly obese (BMI > 40). From 0-10 morbidly obese individuals/100,000/year undergo bariatric surgery. Conclusion: Most countries were found to provide inadequate treatment for obesity.The majority of the morbidly obese are not treated effectively. However, health-care awareness of obesity and bariatric surgeons are slowly increasing.  相似文献   

14.
Background: It has been shown that the depressive effects of both propofol and midazolam on consciousness are synergistic with opioids, but the nature of their interactions on other physiological systems, e. g. respiration, has not been fully investigated. The present study examined the effect of propofol and midazolam alone and in combination with fentanyl on phrenic nerve activity (PNA) and whether such interactions are additive or synergistic. Methods: PNA was recorded in 27 anaesthetised and artificially ventilated rabbits. In three groups, propofol, fentanyl and midazolam were administered intravenously in incremental doses to construct dose-response curves for the depressant effects of each one on PNA. In another two groups, the effect of pretreatment with either fentanyl 1 μg · kg?1 i. v. or midazolam 0.05 mg · kg?1 i. v. on the effects of propofol and fentanyl respectively on PNA were studied. Results: Propofol and fentanyl caused a dose-dependent depression of PNA with complete abolition at the highest total doses of 16 mg · kg?1 i. v. and 32 μg · kg?1 i. v., respectively. In contrast, midazolam in incremental doses to a total of 0.8 mg · kg?1 reduced mean PNA by 63%, but approximately 12% of PNA remained at a total dose as high as 6.4 mg · kg?1. The mean ED50s, calculated from dose-response curves, were 5.4 mg · kg?1, 3.9 μg · kg?1 and 0.4 mg · kg?1 for propofol, fentanyl and midazolam, respectively. Initial doses of either fentanyl 1 μg · kg?1 i. v. or midazolam 0.05 mg · kg?1 i. v. acted synergistically with subsequent doses of either propofol or fentanyl to abolish PNA at total doses of 8 mg · kg?1 and 8 μg · kg?1, respectively. Conclusion: Fentanyl has a synergistic interaction with both propofol and midazolam on PNA and hence potentially on respiration.  相似文献   

15.
Background: Catecholaminergic support is often used to improve haemodynamics in patients undergoing major abdominal surgery. Dopexamine is a synthetic vasoactive catecholamine with beneficial microcirculatory properties. Methods: The influence of perioperative administration of dopexamine on cardiorespiratory data and important regulators of macro- and microcirculation were studied in 30 patients undergoing Whipple pancreaticduodenectomy. The patients received randomized and blinded either 2 μg · kg?1 · min?1 of dopexamine (n=15) or placebo (n=15, control group). The infusion was started after induction of anaesthesia and continued until the morning of the first postoperative day. Endothelin-1 (ET-1), vasopressin, atrial natriuretic peptide (ANP), and catecholamine plasma levels were measured from arterial blood samples. Measurements were carried out after induction of anaesthesia, 2 h after onset of surgery, at the end of surgery, 2 h after surgery, and on the morning of the first postoperative day. Results: Cardiac index (CI) increased significantly in the dopexamine group (from 2.61±0.41 to 4.57±0.78 1 · min?1 · m?2) and remained elevated until the morning of the first postoperative day. Oxygen delivery index (DO2I) and oxygen consumption index (VO2I) were also significantly increased in the dopexamine group (DO2I: from 416±91 to 717±110 ml/m2 · m2; VO2I: from 98±25 to 157±22 ml/m2 · m2), being significantly higher than in the control group. pHi remained stable only in the dopexamine patients, indicating adequate splanchnic perfusion. Vasopressive regulators of circulation increased significantly only in the untreated control patients (vasopressin: from 4.37±1.1 to 35.9±12.1 pg/ml; ET-1: from 2.88±0.91 to 6.91±1.20 pg/ml). Conclusion: Patients undergoing major abdominal surgery may profit from prophylactic perioperative administration of dopexamine hydrochloride in the form of improved haemodynamics and oxygenation as well as beneficial influence on important regulators of organ blood flow.  相似文献   

16.
A concept of balanced analgesia using nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol (acetaminophen), opioids, and corticosteroids can also be used in patients with pre-existing illnesses. NSAIDs are the most effective treatment for acute pain of moderate intensity in children; however, these drugs should be avoided in patients at increased risk for serious side effects, e.g. patients with renal impairment, bleeding tendency, or extreme prematurity. NSAIDs can be given with minimal risks to the younger child with mild to moderate asthma, and, in these patients, the use of steroids can be encouraged; in addition to their antiemetic and analgesic action, a beneficial effect on asthma symptoms can be expected. In the non-intubated child with cerebral trauma, exaggerated sedation caused by opioids and increased bleeding tendency caused by NSAIDs must be avoided. In neonates and small infants, the oral administration of sucrose or glucose is helpful to minimize pain reaction during short uncomfortable interventions.  相似文献   

17.
Background: The efficacy of intraoperative salvage and washing of wound blood and the predictors of allogeneic red cell transfusions in prosthetic hip surgery are insufficiently known.
Methods: In 96 patients, undergoing primary or revision surgery, salvaged and washed red cells and, if necessary, allogeneic blood were used to keep haematocrit not lower than 33%. The bleeding of red cells during hospital stay was calculated from the red cell balance. The preoperative red cell reserve (millilitres of red cells in excess of a haematocrit of 33%) was estimated and the difference between this volume and the total bleeding of red cells was retrospectively used to classify patients with regard to the need for red cells. Stepwise regression analysis was used to define patient-related variables associated with allogeneic blood transfusion.
Results: Preoperative knowledge of the type of operation (primary, revision), the preoperative red cell reserve, and the body mass could predict roughly half of the need for banked blood (r2=0.45). Only one-third of the total bleeding of red cells was retransfused. For complete avoidance of allogeneic blood, autotransfusion was most effective in patients with a moderate need (0–4 u). However, 32% of such patients required allogeneic blood.
Conclusions: Autotransfusion has a limited efficacy to decrease the need for allogeneic blood, and other blood-saving methods should be added for this purpose. It is difficult to predict the need for allogeneic blood preoperatively.  相似文献   

18.
目的    观察缺氧对肾小管上皮细胞分泌外泌体的影响,探讨外泌体在缺氧致肾脏损伤中的作用及机制。 方法    (1)常氧(21% O2)及缺氧(1% O2)分别处理大鼠肾小管上皮细胞(NRK-52E)48 h,收集细胞上清液并使用高速梯度离心法分离外泌体。采用透射电镜、纳米示踪分析、Western印迹、蛋白浓度定量鉴定并比较两组外泌体的基本特性。(2)在共培养实验中,以不同浓度(1、10、50、100、300 mg/L)的常氧外泌体、缺氧外泌体分别干预脂多糖(LPS)诱导的大鼠原代腹腔巨噬细胞,使用实时荧光定量PCR与酶联免疫吸附试验(ELISA)法分别检测巨噬细胞白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)、诱导型氮氧化物合酶(iNOS)水平;使用Western印迹法检测巨噬细胞磷酸化(p)STAT/STAT及细胞因子信号传导抑制蛋白1(SOCS1)的蛋白表达;最后,使用实时荧光定量PCR法检测常氧外泌体与缺氧外泌体中炎性反应相关微RNA(microRNA,miR)的表达差异。 结果    (1)离心得到的囊泡具有外泌体典型的结构,粒径小于150 nm,表达外泌体标志蛋白CD63,说明分离得到外泌体。缺氧对肾小管上皮细胞分泌的外泌体形态、粒径分布比例无明显影响,但提高了外泌体的分泌量。(2)缺氧外泌体相比于常氧外泌体促进了LPS诱导的M1型巨噬细胞IL-6、TNF-α、iNOS 的表达和分泌(均P<0.01),同时提高STAT的磷酸化水平并减少SOCS1的蛋白表达(均P<0.01);对炎性反应相关microRNA检测发现缺氧外泌体中miR-155、miR-27a表达量较常氧外泌体明显升高(P<0.05)。 结论    缺氧可改变外泌体的生物学功能,表现为协同促进LPS诱导的M1型巨噬细胞的表型转化,这可能是慢性肾脏病微炎性反应状态持续的原因之一。  相似文献   

19.
Abstract While flexible-leaflet, central-flow prosthetic heart valves promise relief from anticoagulation therapy, they continue to be restricted by inadequate durability. In consequence, a novel trileaflet valve, made entirely from polyurethane, has been developed. A batch of 6 consecutively manufactured polyurethane valves was subjected to hydrodynamic function and accelerated fatigue testing. Computerized data acquisition and control systems have been introduced to improve valve testing methodologies. In terms of hydrodynamic function, the polyurethane valve demonstrates transvalvular pressure gradients similar to those for a bioprosthetic valve (Carpentier-Edwards) and levels of retrograde flow significantly less than those for either the bioprosthetic valve or a bileaflet mechanical valve (St Jude Medical). The equivalent of 10 years of cycling without failure has been exceeded by all 6 polyurethane valves in accelerated fatigue tests with 2 valves remaining intact after 674 million cycles (equivalent to approximately 17 years) in continuing tests. Highspeed photography revealed considerable differences in leaflet motion between valves cycled at accelerated and physiological rates.  相似文献   

20.
Background: Ventilation during interventional rigid bronchoscopy (IRB) under general anaesthesia (jet ventilation, positive pressure ventilation and spontaneous assisted ventilation) may offer some difficulties. This study compares the effectiveness during IRB of intermittent negative pressure ventilation (INPV) and spontaneous assisted ventilation (SAV). Methods: Thirty-eight patients submitted to IRB were randomised into two groups: SAV or INPV. All patients received a total intravenous anaesthesia; INPV patients were paralysed. Pre-and intra-operative arterial blood gases and O2 flow through a rigid bronchoscope were assessed. The endoscopist applying a subjective score evaluated the operating conditions. Results: Patients of the INPV group, as compared to the SAV group, required a lower dosage of fentanyl (2.6 ± 1.8 (μg · kg?1· h?1 vs. 6.6 ± 4.8 μg · kg?1· h?1), a lower O2 supply (3.3 ± 2.8 1/min vs. 11.6 ± 3.4 1/min), a shorter recovery time (5.4 ± 2.9 min vs. 9.8 ± 7.1 min) and no manually assisted ventilation (0 ± 0 vs. 1 ± 1.1 nd?/procedure). Intraoperative PaCO2 was higher in the SAV (8.1 ± 1.3 kPa) than in the INPV group (5.0 ± 1.6 kPa) and intraoperative pH differed in the two groups (7.26 ± 0.05, SAV vs. 7.47 ± 0.08, INPV). Operating conditions, as assessed by a subjective score, were considered better with INPV than with SAV (4.9 vs. 4.3). Conclusions: As compared to SAV, INPV in paralysed patients during IRB reduces administration of opioids, shortens recovery time, prevents respiratory acidosis, excludes the need for manually assisted ventilation, reduces 02 need and affords optimal surgical conditions. INPV appears a safe, non-invasive and effective ventilatory management during IRB.  相似文献   

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