正常关节软骨和骨关节炎关节软骨细胞中血管活性肠肽表达的比较

背景:神经肽的发现给骨关节炎的治疗带来了新的希望,但神经肽的表达与骨关节炎发病以及软骨退变程度的关系尚不清楚。目的:观察血管活性肠肽在正常关节软骨和不同退变程度骨关节炎软骨中的表达,以及血管活性肠肽表达与骨关节炎发病及软骨退变程度的关系。方法:选取2007-03/11中南大学湘雅医院骨科进行关节置换的骨关节炎患者的关节软骨标本26个,选取因外伤行截肢的膝关节软骨或股骨颈暴力骨折的股骨头正常关节软骨标本10个为对照,根据大体观察凿取正常和骨关节炎不同退变程度软骨块50个,再根据关节软骨改良Mankin病理评分法进行分组,采用免疫组织化学染色检测软骨组织中血管活性肠肽的表达和分布。结果与结论:各关节软骨中均可见到血管活性肠肽阳性神经纤维,正常关节软骨中血管活性肠肽的表达明显高于骨关节炎关节软骨(P<0.05)。且血管活性肠肽表达与软骨改良Mankin病理评分呈负相关(r=-0.896,P<0.05)。说明血管活性肠肽低表达与关节软骨退变程度、骨关节炎病程进展有关,可能是关节软骨退变、骨关节炎发病的机制之一。     

人膝骨关节炎滑膜血管活性肠肽的表达及其与疼痛的关系

目的:研究血管活性肠肽(vasoactive intestinal peptide,VIP)在人膝骨关节炎滑膜中的表达特点,并探讨其与患者膝关节疼痛程度之间的相关性。方法:采集18例骨关节炎患者膝关节滑膜,根据术前视觉模拟疼痛评分(visual analogue scale,VAS)分为轻中度疼痛组(M组)和重度疼痛组(S组),7例外伤病人滑膜作为对照组(C组)。检测患者和正常人滑膜内VIP的含量和位置。结果:正常膝关节和骨关节炎膝关节滑膜均表达VIP,滑膜衬里层和衬里下层的表达无显著性差异(P>0.05)。轻中度疼痛组(M组)滑膜VIP表达高于对照组(C组)和重度疼痛组(S组)(P<0.05)。VIP与疼痛无线性相关。结论:VIP可能在人膝骨关节炎中参与轻度致痛作用,而在重度疼痛中不起主要作用。     

骨关节炎早期软骨退变关节液中IL-32的意义

目研究对象包括膝骨关节炎患者软骨退变Ⅱ、Ⅲ、Ⅳ级的病例数分别为16、11、15,正常人32例,应用ELISA测定IL-32、NO和IL-1在关节滑液中的表达程度。结果 KOAⅡ、Ⅲ、Ⅳ组中关节滑液的IL-32表达均明显高于正常人,有统计学意义（P〈0.01）,其中关节滑液中IL-32与IL-1和NO的关系呈正相关（r=0.45,P〈0.05;r=0.56,P〈0.05）。KOA患者不同程度软骨退变（KOAⅡ、Ⅲ、Ⅳ组）各组敏感度均超过80%,其中以KOAⅢ组最高为90.90%。在一定程度上IL-32可以作为诊断早期软骨退变性骨关节炎（KOAⅢ级）的良好指标。     

血管活性肠肽与消化道疾病研究新进展

血管活性肠肽（Vasoactive Intestinal Peptide，简写VIP），又名舒血管肠肽，分子量3323kU，为一下链肽，属胰高血糖素-胰泌素家族，它在人体内分布较广，属于胃肠道激素，同时又是一种神经肽。近年发现许多免疫活性细胞不仅能释放少量VIP，在其表面也有与VIP高亲和力的受体存在，最近也有研究揭示VIP是神经系统和免疫系统之间相互作用的一种信号分子，在机体免疫，尤其是在局部黏膜免疫中起着一定的作用。VIP对消化道运动起抑制性调节作用。     

基质金属蛋白酶和胶原在创伤关节软骨组织中的表达

背景:研究发现,基质金属蛋白酶和胶原参与关节软骨组织机体生理重建及病理破坏.目的:观察膝关节骨软骨缺损及表面软骨缺损动物模型关节软骨组织中胶原及基质金属蛋白酶的表达变化.方法:雌性SD大鼠48只随机分为3组:骨软骨缺损组在双膝关节制作骨软骨缺损模型,表面缺损组在双膝关节制作表面软骨缺损,对照组双膝关节制作关节囊切开.分别于术后4、8、12周取股骨髁标本,行苏木精-伊红染色,免疫组化检测Ⅰ型胶原、Ⅱ型胶原、基质金属蛋白酶3的表达.结果与结论:骨软骨缺损组术后4周缺损中有少量新生组织生成,8及12周可见到纤维组织填充,修复组织细胞外基质Ⅰ型胶原免疫组化染色阳性,Ⅱ型胶原免疫组化染色阴性,关节软骨组织中基质金属蛋白酶3表达增高.表面缺损组表面软骨缺损4及8周未见修复迹象,12周可见微量纤维组织填充,细胞外基质Ⅰ型胶原免疫组化染色阳性,Ⅱ型胶原免疫组化染色阴性,术后表面缺损组关节软骨组织基质金属蛋白酶3表达增高.对照组关节软骨组织Ⅰ型胶原免疫组化染色阴性,Ⅱ型胶原免疫组化染色阳性,基质金属蛋白酶3低表达,无形态学异常改变.说明机械性损伤可以导致关节软骨细胞外基质成分发生改变,丧失其原有的生物学特性而退变,基质金属蛋白酶3在损伤后的软骨组织中表达增高,使细胞外基质的降解增加,是导致关节软骨退变的重要因素.     

基质金属蛋白酶和胶原在创伤关节软骨组织中的表达

背景：研究发现,基质金属蛋白酶和胶原参与关节软骨组织机体生理重建及病理破坏。目的：观察膝关节骨软骨缺损及表面软骨缺损动物模型关节软骨组织中胶原及基质金属蛋白酶的表达变化。方法：雌性SD大鼠48只随机分为3组：骨软骨缺损组在双膝关节制作骨软骨缺损模型,表面缺损组在双膝关节制作表面软骨缺损,对照组双膝关节制作关节囊切开。分别于术后4、8、12周取股骨髁标本,行苏木精-伊红染色,免疫组化检测Ⅰ型胶原、Ⅱ型胶原、基质金属蛋白酶3的表达。结果与结论：骨软骨缺损组术后4周缺损中有少量新生组织生成,8及12周可见到纤维组织填充,修复组织细胞外基质Ⅰ型胶原免疫组化染色阳性,Ⅱ型胶原免疫组化染色阴性,关节软骨组织中基质金属蛋白酶3表达增高。表面缺损组表面软骨缺损4及8周未见修复迹象,12周可见微量纤维组织填充,细胞外基质Ⅰ型胶原免疫组化染色阳性,Ⅱ型胶原免疫组化染色阴性,术后表面缺损组关节软骨组织基质金属蛋白酶3表达增高。对照组关节软骨组织Ⅰ型胶原免疫组化染色阴性,Ⅱ型胶原免疫组化染色阳性,基质金属蛋白酶3低表达,无形态学异常改变。说明机械性损伤可以导致关节软骨细胞外基质成分发生改变,丧失其原有的生物学特性而退变,基质金属蛋白酶3在损伤后的软骨组织中表达增高,使细胞外基质的降解增加,是导致关节软骨退变的重要因素。     

1例血管活性肠肽瘤患者的护理

血管活性肠肽（ＶＩＰ）瘤很罕见,其以大量水泻、严重低血钾、无胃酸或低胃酸及胰岛细胞瘤为特征的综合征,又名胰性霍乱。我院于１９９８年４月收治１例ＶＩＰ瘤患者,现将护理工作报告如下。１病例介绍 患者男,７１岁,因排水样便 ７～８次／日,体质量下降２０ ｋｇ,经多间医院诊治,疗效欠佳,病情逐渐加重２个月以“腹泻原因待查”收住本科。既往有胆囊炎、十二指肠球部多发性溃疡病史。４月１１日患者呕吐数次为墨绿色胃内容物,予停留胃管持续胃肠减压。４月２０日患者开始发热,３８～４０℃持续１０多天,给予冰敷或酒精拭浴交…     

骨关节炎关节软骨细胞中低氧诱导因子2α及血管内皮生长因子的表达

背景:已有研究发现血管内皮生长因子及低氧诱导因子参与了骨关节炎的发生发展过程,但两者的相关性研究鲜有报道。目的:分析低氧诱导因子2α和血管内皮生长因子在膝骨关节炎患者关节软骨细胞中的表达及相关性。方法:临床收集50例严重膝关节炎接受全膝关节置换患者的膝关节软骨组织标本,根据关节KellgrenLawrance(K-L)X射线分级标准进行分组,其中K-LⅢ级组18例,K-LⅣ级组32例;另取10例因下肢肿瘤或车祸而截肢患者的正常膝关节(K-L分级均为0级)软骨组织标本作为对照组。在苏木精-伊红和Safranin OFast Green染色下进行Mankin整体评分比较各组关节软骨退变程度,免疫组织化学染色检测关节软骨组织细胞中低氧诱导因子2α和血管内皮生长因子的表达,并比较它们的相关性。结果与结论:K-LⅣ级组Mankin整体评分高于K-LⅢ级组和K-L 0级组。免疫组织化学染色显示K-LⅣ级组关节软骨细胞中低氧诱导因子2α和血管内皮生长因子的阳性细胞计数均高于K-LⅢ组和K-L 0级(P<0.05)。低氧诱导因子2α和血管内皮生长因子蛋白在骨关节炎患者关节软骨细胞中表达明显增加,提示低氧诱导因子2α可能上调了靶基因血管内皮生长因子的表达,从而加速了骨关节炎的发生发展。     

胰腺血管活性肠肽瘤1例的护理

胰腺血管活性肠肽瘤是一种少见的胰腺内分泌肿庙,也属于神经内分泌肿瘤,起源于胰岛D1细胞,可分为良性、恶性。由于D1细胞分泌大量胰腺血管活性肠肽,常引起大量水样腹泻、严重低血钾、胃酸缺乏或过少,称为水泻伴低血钾、胃酸缺乏综合征,又称为Verner—Morrison综合征。2008年3月15日,     

肠易激综合征结肠黏膜P物质和血管活性肠肽变化的研究

目的探讨肠易激综合征(IBS)患者结肠黏膜P物质(SP)、血管活性肠肽(VIP)的变化及其在IBS中的可能作用。方法对正常人18例I、BS腹泻型患者20例、便秘型患者22例各取回盲部、乙状结肠黏膜作SP、VIP免疫组织化学染色。结果IBS组患者肠黏膜SP、VIP免疫反应阳性神经纤维较正常对照组增多、增粗,强度增强(P<0.05)。结论IBS患者结肠黏膜SP、VIP水平与腹泻或便秘症状有一定的联系,SP、VIP可能参与IBS的病理、生理过程。     

Effect of vasoactive intestinal polypeptide on the canine cardiovascular system

Our purpose was to determine the effect of vasoactive intestinal polypeptide (VIP) on the cardiovascular system with special emphasis on coronary vascular effects. In section I, VIP was infused into six healthy and six cobalt-cardiomyopathic dogs at two infusion rates (0.02 and 0.05 micrograms/kg/min). Left ventricular end diastolic pressure and mean systemic pressure fell significantly in both groups. Heart rate rose in both, and maximum systolic dP/dt increased in the myopathic group. Cardiac output and regional blood flows were determined by serial left atrial injections of radioactive 15 +/- 3 mum (mean +/- SD) microspheres. In both groups, blood flow increased significantly to the esophagus, pancreas, atria, and ventricles and to the endocardial and epicardial regions of the left ventricular free wall. Blood flow to the brain decreased. In section II, VIP was infused intravenously at 0.1 micrograms/kg/min into six anesthetized dogs with coronary sinus flow, pulmonary artery, and systemic artery catheters inserted. Cardiac index rose from baseline (3.1 +/- 0.5 to 4.8 +/- 1.3 L/min/m2, P less than 0.005), as did coronary blood flow (90 +/- 25 to 159 +/- 54 ml/min, P less than 0.005) during the VIP infusion. Myocardial oxygen consumption rose from 14.1 +/- 3.9 to 19.8 +/- 5.4 ml/min (P less than 0.001), but the aorta-to-coronary sinus O2 difference decreased from 157 +/- 19 ml/L to 132 +/- 42 ml/L (P less than 0.05), and the percent O2 extracted from coronary blood also decreased significantly.(ABSTRACT TRUNCATED AT 250 WORDS)     

胆汁反流与食管下端括约肌组织中一氧化氮及血管活性肠肽的关系

目的探讨胆汁反流与食管下端括约肌组织中一氧化氮及血管活性肠肽的关系。方法对20名健康志愿者及86例反流性食管炎患者,进行食管压力测定、24h食管内pH、食管胆汁监测及食管下端括约肌组织中一氧化氮及血管活性肠肽含量检测;比较健康志愿者、酸反流者、胆汁反流者及混合反流者食管下端括约肌压力、一氧化氮及血管活性肠肽含量的变化。结果酸反流组、胆汁反流组及混合反流组一氧化氮及血管活性肠肽含量较健康志愿者组增多,而混合反流组较酸反流组、胆汁反流组增高(P<0.01);反流性食管炎患者食管下端括约肌压力与食管下端括约肌组织内的一氧化氮及血管活性肠肽呈负相关(r=-88.5,P<0.05和r=-89.9,P<0.05)。结论胆汁反流可导致食管粘膜炎症,食管下端括约肌局部组织中一氧化氮及血管活性肠肽明显增高,食管下端括约肌压力下降,胆汁与胃酸反流具有协同作用,加重食管粘膜损伤。     

Radioimmunoassay of vasoactive intestinal polypeptide (VIP) in plasma.

A sensitive and specific radioimmunoassay for vasoactive intestinal polypeptide (VIP) has been developed, which can detect 3.3 pmol x L-1 of the peptide in plasma. Antisera to highly purified porcine VIP coupled to albumin were raised in eight rabbits. The final dilution, the avidity, and the specificity of each antiserum were determined. 125I-VIP served as label, and highly purified porcine VIP was used as standard. Separtation of antibody-bound and free VIP was achieved by plasma-coated charcoal. Nonspecific interference withe assay system was excluded by extraction of plasma samples with ethanol. The reliability of the assay was investigated by recovery experiments, by serial dilution of plasma samples with high concentration of endogenous VIP, and by immunosorption. The within-and between assay reproducibility at a concentration of 18.3 pmol x L-1 was 1.6 and 2.3 pmol x L-1 (1 S.D.), respectively. Median fasting concentration of VIP in plasma from 74 normal subjects was 7.3 pmol x L-1 (range: 0-20.0 pmol x L-1).     

Human and canine ventricular vasoactive intestinal polypeptide: decrease with heart failure

Vasoactive intestinal polypeptide (VIP) is a systemic and coronary vasodilator that may have positive inotropic properties. Myocardial levels of VIP were assayed before and after the development of heart failure in two canine models. In the first, cobalt cardiomyopathy was induced in eight dogs; VIP (by radioimmunoassay) decreased from 35 +/- 11 pg/mg protein (mean +/- SD) to 5 +/- 4 pg/mg protein (P less than 0.05). In six dogs with doxorubicin-induced heart failure, VIP decreased from 31 +/- 7 to 11 +/- 4 pg/mg protein (P less than 0.05). In addition, VIP content of left ventricular muscle of resected failing hearts in 10 patients receiving a heart transplant was compared with the papillary muscles in 14 patients (five with rheumatic disease, nine with myxomatous degeneration) receiving mitral valve prostheses. The lowest myocardial VIP concentration was found in the hearts of patients with coronary disease (one patient receiving a transplant and three receiving mitral prostheses) (6.3 +/- 1.9 pg/mg protein). The other patients undergoing transplantation had an average ejection fraction of 17% +/- 6% and a VIP level of 8.8 +/- 3.9 pg/mg protein. The hearts without coronary artery disease (average ejection fraction of this group 62% +/- 10%) had a VIP concentration of 14.1 +/- 7.9 pg/mg protein, and this was greater than in hearts of the patients with coronary disease and the hearts of patients receiving a transplant (P less than 0.05). Myocardial catecholamines were also determined in 14 subjects; a weak correlation (r = 0.57, P less than 0.05) between the tissue concentrations of VIP and norepinephrine was noted.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evidence for the interaction between nitric oxide and vasoactive intestinal polypeptide in the mouse gastric fundus.

The involvement of nitric oxide (NO) and vasoactive intestinal polypeptide (VIP) in nonadrenergic noncholinergic (NANC) nerve-induced relaxation and the interaction between NO and VIP were investigated in the mouse gastric fundus. N(omega)-nitro-L-arginine (L-NOARG; 100 microM) completely inhibited the NANC relaxations induced by electrical stimulation (ES) (0.5, 1, 2, 4, and 8 Hz; 25 V; 1 ms; 15-s trains). Hemoglobin (20 microM), hydroxocobalamin (100 microM), and 1H-[1,2,4,]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10 microM) diminished ES-induced relaxations, but alpha-chymotrypsin (10 U/ml) and VIP antiserum (1/200 dilution) had no effect on NANC relaxations. L-NOARG (100 microM) did not have any effect, whereas ODQ (10 microM) attenuated sodium nitroprusside (SNP; 100 nM)-induced relaxations. alpha-Chymotrypsin (10 U/ml) had no effect on the response to SNP. Furthermore, alpha-chymotrypsin (10 U/ml) abolished and VIP antiserum (1/200 dilution) diminished VIP (50 nM)-induced relaxations. L-NOARG (100 microM) caused an inhibition of VIP-induced relaxation that was reversed by L-arginine (1 mM) but not by D-arginine (1 mM). Similarly, ODQ (10 microM) inhibited the responses to VIP. 2-Amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (5 microM) had no effect on these relaxations. L-NOARG (100 microM) and ODQ (10 microM) did not affect isoproterenol (10 nM)-induced relaxations. In conclusion, these results provide evidence that NO is involved in NANC nerve-induced relaxation and the participation of VIP (and related neuropeptides) cannot be excluded in causing relaxation of mouse gastric fundus muscle strips. These findings support the idea that VIP directly stimulates the production of NO by increasing NOS activity and thereby activating soluble guanylyl cyclase in smooth muscle.     

肠易激综合征结肠黏膜P物质和血管活性肠肽变化的研究

背景脑肠肽作为一类具有神经递质和激素双重功能的小分子多肽,在肠易激综合征(IBS)的发病机制中起重要作用。目的探讨肠易激综合征(IBS)患者结肠黏膜P物质(SP)、血管活性肠肽(VIP)的变化及它们在IBS中的可能作用。方法对正常人18例、IBS腹泻型患者20例、便秘型患者22例各取回盲部、乙状结肠黏膜作SP、VIP免疫组织化学染色。结果IBS组患者肠黏膜SP、VIP免疫反应阳性神经纤维较正常对照组增多、增粗,强度增强(P<0.05)。结论IBS患者结肠粘膜SP、VIP水平与腹泻或便秘症状有一定的联系,SP、VIP可能参与IBS的病理生理过程。     

Development of simplified vasoactive intestinal peptide analogs with receptor selectivity and stability for human vasoactive intestinal peptide/pituitary adenylate cyclase-activating polypeptide receptors

Vasoactive intestinal peptide (VIP) is a widespread neurotransmitter whose physiological and pathophysiological actions are mediated by two receptor classes, VIP/pituitary adenylate cyclase-activating polypeptide (VPAC) 1 and VPAC2. VIP is a 28-amino acid peptide that is rapidly degraded and simplified; metabolically stable analogs are needed. In this study, we use information from studies of the VIP pharmacophore for VPAC1/VPAC2 to design nine simplified VIP analogs that could have high affinity and selectivity for each VPAC or that retained high affinity for both VPACs and were metabolically stable. From binding studies of their abilities to directly interact with hVPAC1 (T47D cells, hVPAC1-transfected cells) and hVPAC2 (Sup T1- and VPAC2-transfected cells) and to stimulate adenylate cyclase in each, two analogs [(Ala(2,8,9,11,19,22,24,25,27,28))VIP and (Ala(2,8,9,11,19,24-28))VIP] were found to have >2000- and >600-fold selectivity for hVPAC1. None of the nine analogs had hVPAC2 selectivity. However, two simplified analogs [(Ala(2,8,9,16,19,24))VIP and (Ala(2,8,9,16,19,24,25))VIP] retained high affinity and potency for both hVPACs. 125I-[Ala(2,8,9,16,19,24,25)]VIP was much more metabolically stable than 125I-VIP. The availability of these simplified analogs of VIP, which are metabolically stable and have either hVPAC1 selectivity or retain high affinity for both hVPACs, should be useful for exploring the role of VPAC subtypes in mediating VIPs' actions as well as being useful therapeutically and for exploring the usefulness of VIP receptor imaging of tumors and VIP receptor-mediated tumor cytotoxicity.     

Preferential binding of vasoactive intestinal polypeptide to basolateral membrane of rat and rabbit enterocytes.

Binding of radioiodinated vasoactive intestinal polypeptide (VIP) to intestinal cell membranes of the rabbit ileum and rat jejunum was investigated. Specific binding of 125I-labeled VIP could be demonstrated only on the basolateral membrane and not on the brush border membrane. This corresponded with the lack of an effect on ion transport when VIP was applied to the mucosal side of an in vitro preparation of rabbit ileum. VIP altered ion transport only when it was applied to the serosal side. The binding of 125I-VIP was specific and dependent upon incubation temperature. There was a close correlation between the potency of VIP for inhibition of 125I-VIP binding and that for increasing adenylate cyclase activity. These observations demonstrate that VIP receptors are located on the basolateral membrane.     

Effect of vasoactive intestinal polypeptide on active and passive transport in the human jejunum.

The effect of intravenous vasoactive intestinal polypeptide (VIP) on normal transport mechanisms in the human jejunum in vivo was examined with the triple-lumen, steady-state perfusion technique. By using special test solutions that revealed different aspects of jejunal transport, we were able to evaluate the effect of VIP on specific transport processes, such as active bicarbonate absorption, active chloride secretion, and passive absorption or secretion of sodium chloride. At an infusion rate of 200 pmol/kg per h, VIP inhibited active bicarbonate absorption by approximately 42%, stimulated active chloride secretion to a slight extent, and slightly reduced passive sodium chloride absorption. A larger dose of VIP, 400 pmol/kg per h, had essentially the same effect on active bicarbonate absorption and active chloride secretion, but it markedly depressed passive sodium chloride absorption and also inhibited passive secretion induced by mannitol. VIP reduced the lumen-to-plasma unidirectional sodium and chloride flux rates, while the plasma-to-lumen flux rates were decreased to a lesser extent or remained unchanged. The potential difference became more lumen-negative with VIP, but the sodium diffusion and glucose-stimulated potential were not affected. We conclude that the major effect of VIP in the human jejunum is to decrease the normal absorption of water and electrolytes--not only active bicarbonate-mediated absorption, but also the passive absorption in response to osmotic forces generated by active or facilitated absorptive processes. Although an increase in chloride secretion does occur, this does not appear to be of major importance.