腰椎间盘退变动物模型的研究进展

腰椎间盘突出症是骨科常见疾病，指纤维环破裂后，髓核、纤维环及韧带向腰椎管突出，刺激或压迫神经根，引起患者腰、腿疼痛，病情反复，导致患者活动受限甚至残障，严重影响患者生活质量。而椎间盘退变（intervertebral disc degeneration，IDD）是腰椎间盘突出症的主要原因，相比于腰椎间盘突出症，腰椎IDD更为常见。有大型队列研究显示腰椎IDD发生率男性为31.6%，女性高达44.7%。建立IDD动物模型对人类腰椎IDD的相关研究尤为重要，然而IDD的机制尚不清晰，并且IDD的动物模型繁杂多样，尚无公认的统一且理想的IDD动物模型。根据人类IDD的特点，改变动物腰椎髓核和纤维环理化性质，甚至破坏椎间盘正常结构，诱导动物的椎间盘发生退变。不同的动物模型造模方法各有优劣，模拟人类腰椎IDD的影响因素存在差别，出于不同的研究目的，可以选择适应相关研究的动物模型。笔者对腰椎IDD动物模型的建立方法进行综述，为腰椎IDD的相关研究建立动物模型提供依据。     

腰椎小关节骨性关节炎的研究进展

腰痛不但影响患者的生活质量,还给社会和家庭带来沉重的经济负担。近年,腰痛患病率在不断上升,但对其病因、发病机制等问题仍未达成完全共识。在其复杂多样的病因中,腰椎小关节源性腰痛是一个非常重要的角色。目前关于腰椎小关节骨性关节炎与腰痛的相关性研究,主要集中在腰椎小关节骨性关节炎的流行病学、病理特征、生物力学改变及动物模型等方面,尤其对于动物模型的关注具有很大的意义。腰椎小关节骨性关节炎引起腰痛的发病机制仍存在许多争议,需要更深入的探求和思考。     

压缩应力诱导椎间盘退变动物模型构建的研究进展

正椎间盘退行性疾病(intervertebral disc degenerative disease,IDDD)是目前临床上的常见病,其治疗手段多样,但其发病机制以及变化规律仍不清楚,国内外学者为探寻椎间盘退变规律构建了多种椎间盘退变(intervertebral disc degeneration,IDD)动物模型,按照模型建立方法可大致分为力学模型、损伤模型、生物学模型。但在临床中因椎间盘直接损伤或生物源性椎间盘退变所致腰痛的患者较     

脊柱小关节骨关节炎动物模型的研究进展

腰痛是一种常见的疾病症状,影响人们的正常生活。大约有2/3的人一生中会受到腰痛的困扰。临床上引起腰痛的病因包括腰部肌肉劳损、腰椎间盘退变、腰椎小关节骨关节炎等。其中腰椎小关节骨关节炎被认为是腰痛的常见病因之一。据报告,15%～45%的腰痛患者是由脊柱小关节退变引起的。脊柱小关节又称为关节突关节,在脊柱中与椎间盘构成“三关节复合体”,是脊柱中唯一的滑膜关节。脊柱小关节包括关节面、关节腔、关节囊等结构,在脊柱后部承重中起着重要作用,同时参与脊柱屈伸和旋转运动。目前对于脊柱小关节骨关节炎的研究主要集中在动物模型研究上,通过动物模型模拟脊柱小关节骨关节炎疾病的发生发展。动物模型是研究脊柱骨关节炎疾病的重要工具之一。笔者就目前脊柱小关节骨关节炎动物模型研究进展情况综述如下。     

椎间盘源性腰痛

一、概念的历史演变 什么是“椎间盘源性腰痛”？截止目前尚无统一和明确的定义。腰痛是脊柱及其他系统疾病的常见症状，作为一名骨科医生我们也许对以往给慢性腰痛患者做出的诊断并不陌生，这些诊断包括：慢性软组织劳损、肌纤维组织炎、棘上韧带（棘间韧带）劳损、第三腰椎横突综合征及关节突关节紊乱等。那么椎间盘源性腰痛与上述这些疾病有什么区别呢？目前尚无明确答案。在国外，椎间盘源性腰痛是从椎间盘内紊乱（internal disc disruption，IDD）逐步演变而来的，有学者通过造影技术描述了椎间盘内层纤维环结构紊乱，     

干细胞移植治疗椎间盘退变的研究现状

<正>椎间盘退变（intervertebral disc degeneration,IDD）是与年龄有关、多因素导致的生物学退变,以椎间盘高度的降低、含水量降低、软骨终板钙化、细胞外基质减少等一系列微环境失衡为特点,最终导致椎间盘组织结构完整性丧失、脊柱的活动和功能受限。IDD可导致椎间盘源性腰痛、腰椎间盘突出症、腰椎管狭窄症、退行性腰椎滑脱、     

间充质干细胞治疗椎间盘退行性变的研究进展

<正>椎间盘退行性变(IDD)是引起下腰痛的主要病因之一~([1]),IDD导致的椎间隙狭窄是下腰痛重要发病机制~([2-3])。成人椎间盘是人体最大的无血管组织且细胞含量较少~([4])。IDD不同于正常衰老,衰老属于生理现象,不引起疼痛,而IDD则会引起髓核细胞(NPC)活性下降、数量减少,椎间隙高度丢失等,从而产生下腰痛。IDD的非手术治疗~([5])和手术     

长链非编码RNA基于竞争性内源RNA网络机制调控椎间盘退变的研究进展

腰痛目前已成为困扰全球医疗及社会性问题,严重影响患者生活质量,增加社会负担。40%~50%的腰痛由椎间盘退变（intervertebral disc degeneration,IDD）引起。且IDD的程度与腰痛呈显著正相关。IDD在临床上还可引起椎管狭窄、脊柱节段不稳、椎间盘突出、神经根病和脊髓病等系列疾病。椎间盘（intervertebral disc,IVD）是由上下软骨板（cartilaginous endplates,CEP）、中央的髓核（nucleus pulposus,NP）以及周围的纤维环（annulus fifibrosus,AF）组成,其中NP是由NP细胞、凝胶状的细胞外基质（extracellular matrix,ECM）组成,含水量70%~90%。IDD受异常应力、细胞因子、营养、基因、创伤、环境、年龄等因素的影响。目前对IDD相关疾病的治疗手段包括保守治疗和手术治疗,但二者均存在一定缺陷。虽能改善部分症状,但无法延缓或逆转IDD病理过程。近年来随着分子水平上对IDD机制的研究日益深入,越来越多的证据表明长链非编码RNA（long non-coding RNA,lncRNA）作为竞争性内源RNA（competing endogenous RNA,ceRNA）参与IDD,发挥着重要的调控作用。有学者基于芯片数据分析观察到多种lncRNA在IDD中异常表达,且证实了差异表达的lncRNA在IDD过程中发挥着重大作用。笔者就lncRNA通过ceRNA网络机制影响IDD的研究进展做一综述,为分子水平的诊断及治疗提供新思路。     

间充质干细胞移植治疗椎间盘退变植入途径的研究进展

慢性腰痛（low back pain，LBP）与椎间盘退变（intervertebral disc degeneration，IDD）密切相关，约40%的LBP由IDD引起。IDD的过程主要是髓核细胞活性和数目的减少及细胞外基质（extracellular matrix，ECM）分解，伴各种炎症因子的表达，最终导致椎间盘水分的丢失及高度的降低。IDD也会造成纤维环的破裂或椎间隙变窄，在腰椎IDD的基础上形成的腰椎间盘突出、腰椎管狭窄和腰椎滑脱等，引起LBP。目前LBP的传统治疗包括保守治疗和手术治疗，保守治疗仅能部分缓解临床症状，而手术会导致腰椎活动度的下降和相邻节段椎间盘退变加速等。有研究显示，对于IDD引起的慢性LBP，手术后症状改善情况并不优于保守治疗，均难以控制或逆转IDD的病理过程。干细胞通过内源性修复的机制，可逆转IDD的病理过程。间充质干细胞（mesenchymal stem cells，MSCs）是来源于早期中胚层的具有强大自我更新能力和向分化潜能的成体干细胞集群。因为具有来源广泛、易于提取、分化再生潜能强大、低免疫排斥、低促瘤性等特性，成为细胞治疗的研究热点。随着研究的深入，研究人员发现MSCs有修复退变椎间盘的潜能。MSCs不仅有直接分化为NP细胞的潜能，并且能够通过旁分泌的方式分泌多种细胞因子和生长因子调节椎间盘细胞生长和凋亡、ECM的生成、炎症反应及氧化应激等生理及病理过程，因此MSCs移植疗法成为椎间盘再生和治疗LBP的新型疗法。目前MSCs治疗IDD已经取得一定的成果，但是仍然缺乏一种理想的途径将MSCs植入椎间盘。MSCs的植入途径不仅影响研究结果与可靠性，而且也是后续临床应用的关键因素。笔者就MSCs治疗IDD植入椎间盘的途径综述如下。     

椎问盘退变遗传学机制的研究进展

椎间盘退变性疾病(degenerative disc disease,DDD)是指由椎间盘退变(intervertebral disc degeneration,IDD)引起的以颈肩腰腿疼痛为主要表现的临床症候群,包括了临床上常见的颈、腰椎间盘突出症,颈椎病,退变引起的椎间盘源性腰痛,退变性颈、腰椎不稳症和退变性颈、腰椎管狭窄症等.人的一生中均会出现或轻或重的DDD症状.据资料统计,DDD患者占美国骨科住院人数的1/3以上.了解IDD的发生机制必将为预测和治疗DDD提供最佳途径.     

Vasopressor hormone response following mesenteric traction during major abdominal surgery

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_1α (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.     

A Teaspoon Pump for Pumping Blood with High Hydraulic Efficiency and Low Hemolysis Potential

Abstract: Virtually all blood pumps contain some kind of rubbing, sliding, closely moving machinery surfaces that are exposed to the blood being pumped. These valves, internal bearings, magnetic bearing position sensors, and shaft seals cause most of the problems with blood pumps. The original teaspoon pump design prevented the rubbing, sliding machinery surfaces from contacting the blood. However, the hydraulic efficiency was low because the blood was able to "slip around" the rotating impeller so that the blood itself never rotated fast enough to develop adequate pressure. An improved teaspoon blood pump has been designed and tested and has shown acceptable hydraulic performance and low hemolysis potential. The new pump uses a nonrotating "swinging" hose as the pump impeller. The fluid enters the pump through the center of the swinging hose; therefore, there can be no fluid slip between the revolving blood and the revolving impeller. The new pump uses an impeller that is comparable to a flexible garden hose. If the free end of the hose were swung around in a circle like half of a jump rope, the fluid inside the hose would rotate and develop pressure even though the hose impeller itself did not "rotate"; therefore, no rotating shaft seal or internal bearings are required.     

Microspheres Based Detoxification System: A New Method in Convective Blood Purification

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.     

Tissue perfusion in relation to cardiac output during continuous positive-pressure ventilation and administration of propranolol or verapamil

Background : Our objective was to determine whether administration of propranolol or verapamil modifies the hemodynamic adaptation to continuous positive-pressure ventilation (CPPV), in particular the regional distribution of cardiac output (CO).
Methods : General hemodynamics and regional blood flows assessed by microsphere technique (15 (μm) were recorded in 16 anesthetized pigs during spontaneous breathing (SB) and CPPV with 8 cm H₂O end-expiratory pressure (CPPV8) before and after intravenous administration of propranolol (0.3 mg · kg⁻¹ followed by 0.15 mg · kg⁻¹ · h⁻¹, n=8) or verapamil (0.1 mg · kg⁻¹ followed by 0.3 mg · kg⁻¹ · h⁻¹, n=8).
Results : CPPV8 depressed CO by 25% without shifts in its relative distribution with the exception of a noteworthy increase in adrenal perfusion. Propranolol increased arterial blood pressure, and due to a fall in heart rate, CO dropped by 25%. The kidneys and, to a lesser extent, the splanchic region and central nervous system received increased fractions of the remaining CO at the expense of skeletal muscle flow. Similar patterns were seen during SB and CPPV8 such that the combination of propranolol and CPPV8 depressed CO by 50%. The circulatory effects of verapamil were less evident but myocardial perfusion tended to increase.
Conclusions : The combination of propranolol or verapamil with CPPV does not result in any specific hemodynamic interaction in anesthetized pigs, except that the combined effect of propranolol and CPPV may severely reduce CO.     

Volatile anaesthetics reduce adhesion of blood platelets under low-flow conditions in the coronary system of isolated guinea pig hearts

Background : Inhibitory effects of volatile anaesthetics on platelet aggregation have been demonstrated in several studies. However, the influence of volatile anaesthetics on intracoronary platelet adhesion has not been elucidated so far.
Methods : Isolated hearts of guinea pigs were perfused with buffer in the absence or presence of volatile anaesthetics (0.5 and 1 MAC) at constant coronary flow rates of 5 ml/min for 25 min, then 1 ml/min for 30 min and again 5 ml/min for 10 min. Before, during and after low-flow perfusion, a bolus of human platelets was applied into the coronary system. To simulate thrombogenic conditions, 0.3 U/ml human thrombin was infused during low-flow perfusion and reperfusion. The number of platelets sequestered to the endothelium was calculated from the difference between coronary in- and output of platelets. The myocardial production of lactate and consumption of pyruvate and coronary perfusion pressure were also determined.
Results : At a flow rate of 5 ml/min only about 3% of the applied platelets did not emerge from the coronary system, in any group. In contrast, 13.1±1.2% (mean±SEM) of infused platelets became adherent in low-flow perfusion in the control group without anaesthetic. The adherence was reduced with each 1 MAC isoflurane (to 6.2±1.2%), sevoflurane (to 4.4±0.9%) or halothane (to 3.2±1.5%) (each P <0.05 vs. control). Volatile anaesthetic, 0.5 MAC, did not inhibit platelet adhesion to a statistically significant extent in any case. Perfusion pressure and metabolic parameters were not statistically different between the control and the hearts exposed to anaesthetics.
Conclusion : Volatile anaesthetics in a concentration of 1 MAC can reduce the adhesion of platelets in the coronary system under reduced flow conditions. This action does not arise from vasodilation or inhibition of ischaemic stress.     

Bariatric Surgery in Some "Central and East-European (former Eastern bloc)"Countries - Current Status and Prediction for the Next Millennium

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.     

Is the recovery profile of mivacurium independent of the rate of decay of its plasma concentration in patients with normal plasma cholinesterase activity?

Background: The duration of action of muscle relaxants is poorly correlated to the rate of decay of their plasma concentration. The plasma concentration of mivacurium may rapidly decrease below its active concentration because of the extensive hydrolysis of mivacurium. By inflating a tourniquet on one upper limb for 3 min after the administration of atracurium, mivacurium or vecuronium, we studied the influence of the initial decline of their plasma concentration on their effect. Methods: In 50 patients anaesthetised with thiopental, isoflurane and fentanyl, the effect of bolus doses of 0.15 or 0.25 mg . kg^?1 mivacurium (MIV 15, MIV 25), 0.3 or 0.5 mg . kg^?1 atracurium (ATR 30, ATR 50) and 0.06 or 0.1 mg . kg^?1 vecuronium (VEC 06, VEC 10) were measured on both arms (evoked response of the adductor pollicis to train-of-four stimulation every 12 s), a tourniquet being applied on one arm just before and during 3 min after the muscle relaxant bolus. Results: Tourniquet inflation of 3 min almost abolished the neuromuscular effect of mivacurium. In the vecuronium groups and in the ATR 50 group, tourniquet inflation did not modify the maximum degree of depression of the twitch response. Also, the duration of action of vecuronium was unaffected by the tourniquet. In the ATR 30 group, times to return of the twitch response to 25% (duration 25%) and 75% (duration 75%) of control response were significantly shorter in the cuffed arm, 23 min vs 27 min, and 41 min vs 45 min, respectively. In the ATR 50 group, only duration 25% was significantly shorter in the cuffed arm (41 min vs 45 min). Conclusion: The results suggest that the rate of decline of the plasma concentration of mivacurium is so rapid, that a very low and almost clinically ineffective concentration is present as soon as 3 min after its administration. The results also indicate that the recovery from a mivacurium-induced neuromuscular blockade is not influenced by the rate of decay of its plasma concentration in patients with genotypically normal plasma cholinesterase.     

Membranes in Artificial Organs

Abstract: Membrane processes play a pivotal and enabling role in modern replacement therapy for acute and chronic organ failure and in the management of immunologic diseases. In fact, virtually all contemporary extracorporeal blood purification methods employ membrane devices, and the next generation of artificial organs and tissue engineering therapies are almost certain to be similarly grounded in membrane technology. In this short essay, we comment on the similarities and differences among synthetic membranes and their natural counterparts and also provide a critical overview of the demographics and technology of hemodialysis, hemofiltration, apheresis, oxygenation, and emerging membrane technologies and applications.     

Influence of dopexamine hydrochloride on haemodynamics and regulators of circulation in patients undergoing major abdominal surgery

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.     

Synergistic interaction between the effects of propofol and midazolam with fentanyl on phrenic nerve activity in rabbits

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.