眼络通方对兔视网膜静脉阻塞模型促血管新生因子PDGF、VEGF表达的影响

[目的]探讨眼络通方对视网膜静脉阻塞(retinal vein occlusion,RVO)新西兰兔视网膜血管新生的影响。[方法]将48只健康新西兰兔随机分为空白对照组12只和模型组36只,模型组以氩激光光凝,建立RVO模型,并随机分为模型对照组、天保宁组、眼络通组,每组各12只。空白对照组及模型对照组予0.9%氯化钠溶液灌胃5mL/(kg·d);天保宁组灌胃给药剂量为0.02g/(kg·d);眼络通组灌胃给药剂量6.9g/(kg·d),连续给药4周。分别于灌胃治疗第1、2、4周后每组各处死4只新西兰兔,以免疫组化与Western blot法检测视网膜组织血小板源性生长因子(platelet-derived growth factor,PDGF)、血管内皮细胞生长因子(vascular endothelial growth factor,VEGF)的蛋白表达,实时荧光定量PCR (real-time quantitative polymerase chain reaction,RT-PCR)检测视网膜组织PDGF、VEGF的mRNA表达,并对相关数据进行统计学分析。[结果]与空白对照组比较,模型对照组1、2、4周各时相视网膜组织中PDGF、VEGF蛋白与mRNA表达量均显著升高(P0.05);与模型对照组比较,眼络通组1、2、4周各时相视网膜组织中PDGF、VEGF蛋白与mRNA的表达量均显著降低(P0.05),但仍显著高于空白对照组(P0.05);而天保宁组各时相视网膜组织中PDGF、VEGF蛋白与m RNA的表达量差异无统计学意义(P0.05)。[结论]眼络通方通过抑制视网膜组织VEGF、PDGF的表达,减少促血管新生因子释放,从而抑制视网膜血管新生,发挥保护视网膜、治疗RVO的作用。     

京万红软膏上调PDGF mRNA表达改善大鼠缺血合并外伤型糖尿病足的研究

目的考察京万红软膏对大鼠缺血合并外伤型糖尿病足的疗效及作用机制。方法建立糖尿病大鼠模型,在此基础上建立大鼠缺血合并外伤型糖尿病足模型。实验设置4组,每组大鼠15只,分别为假手术组、模型组、京万红软膏组、重组人表皮生长因子外用溶液(rhEGF)组。给药14 d,记录给药前后大鼠体质量、血糖、足部形态及溃疡面积的变化情况。并于给药后取足部溃疡部位组织行HE染色,采用RT-PCR法检测京万红软膏对血小板源性生长因子(PDGF)、血管内皮生长因子(VEGF)及其受体FLT-1 mRNA表达的影响。结果京万红软膏对大鼠缺血合并外伤型糖尿病足具有消肿生肌,促进创面愈合的功效。与模型组相比,京万红软膏组给药14 d后可极显著减少大鼠足部外伤部位的溃疡面积(P0.01);可极显著上调PDGF mRNA的表达(P0.01)。结论京万红软膏对大鼠缺血合并外伤型糖尿病足具有促进伤口愈合的功效,可能与上调PDGF mRNA的表达相关,但对VEGF及其受体Flt-1 mRNA的表达没有影响。     

Weak association of the platelet-derived growth factor beta (PDGFB) and PDGF receptor beta (PDGFRB) genes with schizophrenia and schizoaffective disorder

Abstract

Schizophrenia is a severe neuropsychiatric disorder with diverse characterization of symptoms. Extensive research has been performed to elucidate the etiology of schizophrenia. One of the most convincing hypotheses comes from the dopaminergic system although none of the core genes has been consistently positive in association studies. Objective. In this investigation, we explored the possibility that the genes for platelet-derived growth factor beta (PDGFB) and its receptor (PDGFRB) might play an important role in the development of schizophrenia based on previous reports pointing to their ability to interact with the dopamine D₂/D₄ and NMDA receptors as well as their role in neurite outgrowth. Methods. We investigated the association of variants around these genes with schizophrenia and schizoaffective disorder in 104 small nuclear families using the Sib-Transmission Disequilibrium Test (TDT-STDT). Furthermore, quantitative trait analysis using family-based association test was applied to determine possible association of age at onset (AAO). Results. Allele G in PDGFRB(rs758588) was associated with AAO (P=0.019). An over-transmission of allele T in PDGFB(rs130650) polymorphism (P=0.043) and an over-transmission of allele A in PDGFRB(rs6865659) polymorphism (P=0.046) were observed. Furthermore, the combined TDT-STDT yielded consistent results. Conclusion. Overall, PDGFB and PDGFRB genes might play a role in the etiology of schizophrenia.     

血小板衍化生长因子在铒激光制备的骨缺损愈合过程中的表达研究

目的：探讨不同能量的铒激光切割骨组织骨愈合过程中血小板衍化生长因子（PDGF）的表达情况。方法：选择8只兔子,在兔子的颅盖骨上制备直径2mm的4个圆形骨缺损。激光组：能量100mJ,200mJ,400mJ的铒激光分别制备的骨缺损,对照组：种植手机制备的骨缺损。于术后1周,3周,4周,6周分别处死2只兔子取样本,应用免疫组织化学染色法观察PDGF的表达情况。结果：术后1,3周100m．1激光组平均灰度值与200mJ,400mJ激光组及对照组平均灰度值比较差异有统计学意义（P〈0．05）;术后4,6周激光组之间及与对照组平均灰度值比较差异无统计学意义（P〉0．05）。结论：铒激光制备的骨缺损愈合过程中PDGF的表达较传统种植手机组高,且能量为200mJ时PDGF的表达最高。     

Use of Imatinib in the Prevention of Heterotopic Ossification

Background

Heterotopic ossification (HO) is a common complication following orthopedic and trauma surgery, which may have substantial negative effects on the postoperative outcome. Angiogenesis appears to play a critical role in heterotopic ossification. One of the involved signaling molecules is platelet-derived growth factor (PDGF) which may be inhibited by imatinib.

Questions/Purposes

Our goal was to prevent HO by pharmacologically interfering with the molecular signaling pathways involved in the developmental process. We hypothesized that by administering a proven inhibitor of PDGF expression, heterotopic bone formation may be prevented.

Methods

The effect of imatinib on HO formation was studied in a murine model which reliably produces islets of HO within the soft tissue following Achilles tenotomy. The control group underwent Achilles tenotomy only. The imatinib group received imatinib mesylate. After trial completion, the limbs were harvested and scanned by micro-CT. Heterotopic bone volume was then identified and quantified.

Results

The mean volume of heterotopic bone formed in the control group was 0.976mm³ compared to 0.221 mm³ in the imatinib group. The volume of HO in the treatment group was reduced by 85% compared to the control group.

Conclusions

The administration of imatinib was associated with a significantly reduced volume of HO. This may be due to the inhibitory effect of imatinib on the PDGF signaling pathway during development of HO.

Clinical Relevance

The successful reduction of HO formation following imatinib administration has led to further insight concerning the pathogenesis of HO which in the future may lead to new clinical approaches towards the prevention of HO.

Electronic supplementary material

The online version of this article (doi:10.1007/s11420-013-9335-y) contains supplementary material, which is available to authorized users.     

VEGF、EGFR、PDGF在人脑胶质瘤中的表达及其与恶性程度和预后的关系

目的：探讨血管内皮生长因子(VEGF)、表皮生长因子受体(EGFR)、血小板衍生生长因子(PDGF)在人脑胶质瘤中的表达及其与肿瘤恶性程度和患者预后的关系。方法选取我院神经外科2010年11月至2013年8月手术切除并经病理证实的脑胶质瘤标本68例及同期正常脑组织标本12例,采用SP免疫组化法检测所有标本中VEGF、EGFR、PDGF的表达,分析其与胶质瘤各临床特征的关系,采用Spearman等级相关分析方法分析VEGF、EGFR、PDGF三者间的关系。结果胶质瘤组织中VEGF、EGFR和PDGF的表达阳性率分别为63.24%(43/68)、51.47%(35/68)和52.94%(36/68),均明显高于正常脑组织的0(0/12)、8.33%(1/12)和33.33%(4/12),差异均有统计学意义(P<0.05);在生存率方面,VEGF阳性患者低于VEGF阴性患者(23.26%vs 60.00%),EGFR阳性患者低于EGFR阴性患者(28.57%vs 51.52%),PDGF阳性患者低于PDGF阴性患者(27.78%vs 62.50%),差异均有统计学意义(P<0.05);Spearman等级相关分析显示,VEGF、EGFR及PDGF的表达与胶质瘤WHO分级呈显著正相关(rVEGF=0.428, rEGFR=0.407,rPDGF=0.431,P<0.05)。结论 VEGF、EGFR、PDGF在人脑胶质瘤发生发展中起重要调节作用,可作为判断胶质瘤恶性程度和预后的重要生物学参考指标。     

Metabolic syndrome: pathogenesis, medical care and dental implications

BACKGROUND: The dental literature contains little information about metabolic syndrome (MetS) and its dental implications. TYPES OF STUDIES REVIEWED: The authors conducted a MEDLINE search for the period 2000 through 2005, using the term "metabolic syndrome" to define its pathophysiology, medical treatment and dental implications. RESULTS: MetS is the co-occurrence of abdominal obesity, hyper-triglyceridemia, reduced high-density lipoprotein cholesterol levels, hypertension and impaired fasting glucose, which results from consumption of a high-calorie diet and decreased levels of physical activity superimposed on the appropriate genetic setting. Components of MetS synergistically promote the development of atherosclerosis, resulting in myocardial infarction and stroke. CLINICAL IMPLICATIONS: Deteriorating oral health status is associated with worsening of the atherogenic profile. Tooth loss often results in chewing difficulties because of inadequate occlusive surfaces and may lead to alterations in food selection and dietary quality. This, in turn, adversely affects body composition and nutritional status, both of which are related to vascular health. Dentists should develop treatment plans that preserve and restore the dentition, thus ensuring maximum masticatory efficiency and affording patients the optimum opportunity to consume food that will not foster atherogenesis.     

PDGF Receptor Signaling in Osteoblast Lineage Cells Controls Bone Resorption Through Upregulation of Csf1 Expression

The physiological functions of platelet-derived growth factor receptors (PDGFRs) α and β in osteoblast biology and bone metabolism remain to be established. Here, we show that PDGFRA and PDGFRB genes are expressed by osteoblast-lineage canopy and reversal cells in close proximity to PDGFB-expressing osteoclasts within human trabecular bone remodeling units. We also report that, although removal of only one of the two PDGFRs in Osterix-positive cells does not affect bone phenotype, suppression of both PDGFRs in those osteoblast lineage cells increases trabecular bone volume in male mice as well as in female gonad-intact and ovariectomized mice. Furthermore, osteoblast lineage-specific suppression of PDGFRs reduces Csf1 expression, bone marrow level of macrophage colony-stimulating factor (M-CSF), number of osteoclasts, and, therefore, bone resorption, but does not change bone formation. Finally, abrogation of PDGFR signaling in osteoblasts blocks PDGF-induced ERK1/2-mediated Csf1 expression and M-CSF secretion in osteoblast cultures and calcitriol-mediated osteoclastogenesis in co-cultures. In conclusion, our results indicate that PDGFR signaling in osteoblast lineage cells controls bone resorption through ERK1/2-mediated Csf1 expression. © 2020 American Society for Bone and Mineral Research (ASBMR).     

PDGF and TGF-β promote tenascin-C expression in subepithelial myofibroblasts and contribute to intestinal mucosal protection in mice

Background and Purpose: Tenascin-C (TnC) is a multi-domain extracellular matrix glycoprotein that is expressed at a high level during embryogenesis but is almost absent during normal postnatal life. This multi-domain complex molecule is reported to associate with both pro-inflammatory and anti-inflammatory signalling cascades. In this study, we examined how TnC modulated intestinal inflammation.Experimental Approach: TnC pathophysiology was evaluated in cultures of rat intestinal subepithelial myofibroblasts (ISEMF) and intestinal epithelial cells. Wild-type and TnC(−/−) mice were treated with dextran sodium sulfate (DSS) to induce colitis.Key Results: DSS-induced colitis in mice markedly increased TnC in the damaged mucosal areas and up-regulated mRNA for TnC, pro-inflammatory cytokines and growth factors (PDGF-B and TGF-β1). In addition, 2,4,6-trinitrobenzene sulfonic acid-induced colitis and SAMP1/Yit mice, a model of spontaneous Crohn''s disease, also exhibited increased mucosal TnC in colon and ilea respectively. PDGF receptor-α (PDGFRα) positive ISEMF were the primary TnC-producing cells in colon tissues. Accordingly, ISEMF collected from the rat colon constitutively expressed both TnC and PDGFRα. PDGF-BB and TGF-β1 up-regulated both TnC mRNA and protein levels in ISEMF. Knock-down of TnC gene increased susceptibility to DSS-induced colitis, compared with TnC(+/+) littermates. TnC(−/−) mice showed marked abrasion of intestinal mucosal barrier and increased inflammatory scores. Moreover, TnC accelerated both trans-well migration and wound healing in epithelial cells.Conclusions and Implications: The pharmacological profiles of PDGF-BB and TGF-β in colitis tissues and ISEMF suggest that increased TnC production during inflammation contributed to epithelial cell migration, remodelling and protection of intestinal barriers.