PM2.5对骨质疏松症的影响研究

骨质疏松症是以骨量减少、骨微细结构破坏为特征,导致骨脆性增强和骨折危险度增高的代谢性骨骼疾病,是由于骨形成和骨吸收过程出现动态失衡引起。雌激素受体存在于骨髓基质细胞、成骨细胞、破骨细胞中,在调节骨代谢方面有着重要的作用。PM_(2.5)又称大气细颗粒物,易附带有毒、有害物质如二噁英等多环芳烃类化合物,可随呼吸通过肺泡进入毛细血管,再进入整个血液循环系统,引发一系列炎症和氧化损伤反应,或可刺激破骨细胞增殖,破坏机体成骨和破骨的平衡调节,或可作为ER的诱导配体,直接或间接地与转录因子相互作用,从而干扰基因的转录,引起或加剧骨质疏松症。     

2,3,7,8-四氯二苯并对二噁英对骨代谢的影响及机制的研究进展

2,3,7,8-四氯二苯并对二噁英（2,3,7,8-tetrachlorodibenzo-p-dioxin,TCDD）是一类毒性极强的二噁英类化合物,能在人体富集,对生殖系统、免疫系统、骨代谢等多方面产生严重毒性。近年来,大量动物试验和体外试验已经证实,骨是TCDD的敏感靶点,TCDD能引起骨形态结构、骨密度和骨生物力学等特征的改变。TCDD可通过芳香烃受体（aryl hydrocarbon receptor,AhR）介导的不同信号通路,如RANKL、MAPK、Wnt等影响成骨细胞和破骨细胞的增殖分化,干扰骨代谢,破坏骨重建,诱发骨物理性质的病理改变及骨质疏松等相关骨代谢疾病。此外,TCDD的抗雌激素效应( anti-estrogen effect)也在成骨细胞的生成及骨量丢失中起着重要的调节作用。但目前,TCDD影响骨代谢的机制尚未彻底阐明,并且TCDD所介导的各通路之间的相互作用和联系也有待进一步探究,明确相关的分子机制和信号通路可能会为骨代谢疾病的临床治疗提供新思路。本文将总结TCDD对骨物理特性、骨细胞发育与骨代谢产生的影响,并阐述TCDD可能介导的不同信号通路及机制对成骨细胞、破骨细胞生成的调控作用,为临床研究和治疗提供更系统的理论依据。     

芳香烃受体在免疫调节中的作用及与程序性死亡受体1的联系

芳香烃受体(AhR)是一种配体依赖性转录因子,不同的配体介导不同甚至截然相反的作用。AhR配体种类以及来源多样,可以在细胞周期、机体生长发育、免疫细胞分化等方面发挥重要作用,其中在肿瘤免疫中发挥的调节作用尤为突出。近年来,程序性死亡受体1(PD-1)作为一种重要的免疫抑制分子,其通过与配体1(PD-L1)结合启动PD-1/PD-L1信号通路,在肿瘤免疫逃逸、器官移植排斥与自身免疫性疾病的发生发展中发挥不同作用。AhR通过与配体结合调节淋巴细胞向不同方向分化,影响PD-1/PD-L1表达,从而调节免疫系统。本文对AhR在生理和病理情况下如自身免疫性疾病、肿瘤、移植等所发挥的免疫学作用进行综述,并对AhR和PD-1之间可能存在的联系进行分析展望。     

雌激素受体相关受体α与骨代谢

雌激素受体相关受体α(estrogen receptor-related receptorα,ERRα)是最早发现的一种孤儿核受体,是核受体超家族中一员。它与雌激素受体(estrogen receptors,ERs)有着一定的同源性,但尚未发现任何配体。目前研究证明ERRα在骨代谢、能量代谢的调节以及乳腺癌发生中都起到重要作用。本文主要综述ERRα在骨代谢方面的研究进展,特别是在骨组织中对受体介导的雌激素信号途径的参与,以求进一步了解雌激素调控骨改建的机制,以及展望ERRα作为靶点治疗雌激素相关的骨代谢病的前景。     

增强创伤后小鼠巨噬细胞的芳香烃受体表达对炎症因子水平和杀菌能力的影响

目的探讨严重创伤后小鼠腹腔巨噬细胞(PM)中芳香烃受体(AhR)的表达规律并分析增强创伤后PM的AhR表达对炎症因子水平和杀菌能力的影响。方法采用实验研究方法。取40只6～8周龄雄性C57BL/6J小鼠(小鼠周龄、性别、品系下同), 按随机数字表法(分组方法下同)分为对照组、创伤后2 h组、创伤后6 h组、创伤后12 h组, 每组10只。将后3组小鼠构建骨折+失血的严重创伤模型, 对照组小鼠不做处理。分别在未创伤和创伤后2、6、12 h时, 提取对照组、创伤后2 h组、创伤后6 h组、创伤后12 h组小鼠原代PM(提取细胞下同), 分别采用蛋白质印迹法和实时荧光定量反转录PCR法检测AhR的蛋白和mRNA表达, 采用转录组测序分析AhR信号通路相关分子的基因表达。取20只小鼠分为对照组、创伤后6 h组, 每组10只, 提取PM后, 采用免疫沉淀法检测AhR泛素化水平。取12只小鼠, 分为单纯二甲基亚砜(DMSO)组、创伤后6 h+DMSO组、单纯MG-132组、创伤后6 h+MG-132组, 每组3只, 并行相应处理后, 提取PM, 采用蛋白质印迹法检测AhR蛋白的表达。取20只小鼠构...     

大气细颗粒物对小鼠皮肤组织中表皮生长因子受体mRNA表达的影响

目的:研究大气细颗粒物对小鼠皮肤组织表皮细胞生长因子受体(epidermal growth factor receptor,EGFR)m RNA表达的影响,以探讨大气细颗粒物对皮肤老化的影响。方法:将40只BALB/c雌性小鼠随机分成生理盐水对照组及大气细颗粒物(PM2.5)染毒低、中、高剂量(分别为1.6、8.0和40.0mg/kg)组,每组10只。各剂量组均经气管滴注染毒3d。末次染毒24h后,采用实时荧光定量PCR方法分别检测各组小鼠皮肤组织EGFR m RNA的表达量。结果:与对照组相比,PM2.5染毒中、高剂量组EGFR m RNA的表达量均明显升高(P0.05),且与剂量呈正相关。结论:中、高浓度PM2.5可以诱导EGFR m RNA的表达,促进皮肤老化的发生。     

色氨酸2,3-双加氧酶在色氨酸分解代谢及免疫调节中的作用

色氨酸2,3-双加氧酶(TDO)是催化色氨酸由犬尿氨酸(Kyn)途径分解代谢的限速酶.TDO主要在肝内降解色氨酸,调整体内色氨酸水平,能够抑制T细胞增殖,参与抗菌及炎性反应.代谢产物Kyn为芳烃受体(AhR)的内源性配体,TDO-Kyn-AhR通路具有调节肿瘤生长作用.随着对TDO介导色氨酸代谢免疫机制研究的不断积累,其在肿瘤治疗及移植免受耐受领域的应用前景令人期待.本文就TDO介导的色氨酸分解代谢及免疫调节作用进行综述.     

中药通过调控短链脂肪酸防治骨质疏松症的研究进展

肠道菌群微生物是与宿主共生的一个大的生物群落，当其发生紊乱时将会导致多种疾病的发生，尤其是全身代谢性疾病。其代谢产物也对全身代谢性疾病起到重要的调控作用，尤其是骨代谢性疾病。短链脂肪酸(short chain fatty acids, SCFAs)是肠道微生物群所产生的一类代谢产物，能够很好地反映肠道菌群微生物的功能，大量的研究证明其在骨代谢性疾病中起着调控作用。中药在调控肠道菌群微生物及其代谢产物中有很大的作用，尤其是对于SCFAs的调控。笔者就单味中药及提取物与中药复方通过调控SCFAs影响骨代谢，从而在防治骨质疏松症方面的研究进行总结，以期为骨质疏松症的预防和治疗提供新思路。     

孕期PM2.5暴露对子代出生体重影响的研究进展

PM2.5是空气污染物的重要组成部分,其对全身各系统器官都会产生不同的危害。孕期PM2.5暴露会导致胚胎先天畸形、早产、胎儿出生体重异常等不良妊娠结局,严重时导致新生儿死亡。大量流行病学研究表明,孕期PM2.5暴露与子代出生体重变化之间存在相关性。PM2.5可能通过血管重构、炎症、氧化应激、免疫、表观遗传等机制影响胎儿的出生体重,但其作用机制尚不清楚。另外也应该考虑在高浓度的PM2.5环境下,人类外出活动减少等主观社会行为因素对胎儿出生体重的影响。目前尚无明确的药物防治以减轻或预防PM2.5所致的健康危害。控制环境PM2.5污染仍是有效预防PM2.5暴露导致各种不良妊娠结局的重要举措。     

肿瘤坏死因子受体相关因子6与骨代谢的研究进展

TRAF6是肿瘤坏死因子受体相关因子家族(TRAFs)中既可与肿瘤坏死因子受体(TNFR)超家族结合,又可与白细胞介素-1受体/Toll样受体(IL-1R/TLR)超家族相互作用来传递细胞外信号的一种细胞内接头蛋白,在炎症反应、免疫应答、骨代谢中发挥着重要作用。本文现就TRAF6在骨代谢中的研究进展作一综述。     

Dynamics of surgical smoke in the operating room during spinal surgery: Comparison of particulate matter 2.5-air concentration between the electric scalpel with and without a smoke evacuation pencil: A cross-sectional study

BackgroundSurgical smoke is a vaporous by-product generated during tissue incision and cauterization with an electric scalpel. This smoke contains tissue- and blood/vascular-derived substances, bacteria, viruses, and chemical substances. Among them, it contains many fine particles called particulate matter (PM) 2.5, which are harmful and hazardous to the human body. We aimed to investigate the occurrence of PM2.5 in surgical smoke produced during spinal surgery and to evaluate the efficacy of an electric scalpel with a smoke evacuation pencil.MethodsIn this retrospective observational study, 89 patients who underwent spinal surgery between June 2019 and May 2021 were included. A dust monitor was installed in the operating room to measure the PM2.5 air concentration during the surgery. During each surgery, the total amount of PM2.5, the maximum PM2.5 air concentration, the exposure time to PM2.5, and the average value of PM2.5 air concentration from the start to the end of the surgery were calculated.ResultsWe found that in 29 of the 89 cases (32.6%), the air concentration of PM2.5 increased to a level that could cause health damage during the surgery. Twelve cases (13.4%) reached the level that could cause serious health damage, and 8 cases (9%) reached an emergency warning level. The total amount and the maximum and average levels of PM2.5 were significantly suppressed in the surgery with a smoke evacuation pencil group than in the surgery without a smoke evacuation pencil group.ConclusionWe detected hazardous levels of PM2.5 in the air during spinal surgery, highlighting the importance of considering smoke control or reduction during spinal surgery. We recommend using an electric scalpel with a smoke evacuation pencil for regulating PM2.5 levels in the operating room.     

The amazing osteocyte

The last decade has provided a virtual explosion of data on the molecular biology and function of osteocytes. Far from being the “passive placeholder in bone,” this cell has been found to have numerous functions, such as acting as an orchestrator of bone remodeling through regulation of both osteoclast and osteoblast activity and also functioning as an endocrine cell. The osteocyte is a source of soluble factors not only to target cells on the bone surface but also to target distant organs, such as kidney, muscle, and other tissues. This cell plays a role in both phosphate metabolism and calcium availability and can remodel its perilacunar matrix. Osteocytes compose 90% to 95% of all bone cells in adult bone and are the longest lived bone cell, up to decades within their mineralized environment. As we age, these cells die, leaving behind empty lacunae that frequently micropetrose. In aged bone such as osteonecrotic bone, empty lacunae are associated with reduced remodeling. Inflammatory factors such as tumor necrosis factor and glucocorticoids used to treat inflammatory disease induce osteocyte cell death, but by different mechanisms with potentially different outcomes. Therefore, healthy, viable osteocytes are necessary for proper functionality of bone and other organs. © 2011 American Society for Bone and Mineral Research.     

PM 2.5对去卵巢骨质疏松症大鼠骨密度和生物力学性能的影响

目的 探讨PM 2.5对去势致骨质疏松症大鼠腰椎（L3~5）、右侧股骨骨密度及左侧股骨骨生物力学特性的影响。方法 将3周龄雌性SD大鼠（SPF级）适应生长一周后随机分为假手术组、模型对照组和PM 2.5低、中、高剂量组,行气道滴注PM 2.5混悬液或生理盐水,滴注5个月后将模型对照组和PM 2.5各剂量组通过切除大鼠双侧卵巢建立绝经后骨质疏松症模型,假手术组仅切除卵巢周围约1 g的脂肪组织。继续气管滴注至第9个月末,其间分别测定去势后滴注第7、9个月末各组腰椎（L3~5）、右侧股骨骨密度(bone mineral density,BMD)数值,处死大鼠后取左侧股骨进行三点弯曲试验。结果 气管滴注7个月后, 各组大鼠腰椎（L3~5）及右侧股骨 BMD 比较差异无统计学意义 (P>0.05)。滴注9个月后, PM 2.5各剂量组大鼠腰椎及右侧股骨 BMD 明显低于模型对照组,且PM 2.5各剂量组之间呈现一定的剂量关联趋势,中、高剂量组BMD降低趋势明显,差异有统计学意义 (P<0.05)。此外,从骨生物力学角度分析,与假手术组相比,模型对照组、PM 2.5低剂量组的弹性载荷、极限载荷、弹性模量均下降,且差异有统计学意义( P＜0.05) ;与模型对照组比较,PM 2.5各剂量组的股骨弹性载荷、极限载荷和弹性模量降低( P＜0. 05),下降趋势与BMD一致,高剂量组下降最为显著。结论 PM 2.5加速了去势大鼠的骨密度降低,造成骨生物力学破坏,与PMOP的严重程度相关,具体机制有待探讨。     

Bone Health in Women With Polycystic Ovary Syndrome: A Narrative Review

Bone as an active connective and endocrine tissue is influenced by hormones, physical activity, inflammatory factors, minerals, dietary components, and body weight. Bone fractures are a major cause of decreased quality of life and mortality in humans. Polycystic ovary syndrome (PCOS), is one of the most common endocrine disorders in women of reproductive age worldwide. PCOS is associated with disturbances in androgen and estrogen levels, insulin resistance (IR), obesity, as well as low-grade chronic inflammation, and gut microbiota (GM) dysbiosis, all of which may negatively or positively affect bone metabolism. However, it has not yet been well clarified whether PCOS is bone-protective or bone-destructive. This study aimed to review the association between bone health and PCOS, and summarize its related factors. PubMed, Scopus, and Web of Science databases were searched to retrieve relevant English publications investigating the relationship between bone health and PCOS. Several disorders associated with PCOS can negatively or positively affect bone metabolism. Despite some positive effects of insulin, androgens, estrogens, and obesity on bone, IR, estrogen deficiency, low-grade chronic inflammation, and GM dysbiosis may adversely affect the bone metabolism in PCOS women. Studies comparing bone mineral density or bone metabolism and the risk of bone fractures in women with PCOS have controversial results. Further studies are required to understand the mechanisms underlying bone metabolism in PCOS subjects. Moreover, prospective studies are needed to estimate the risk of bone fractures and osteoporosis in PCOS subjects.     

脂代谢紊乱与骨质疏松症的关系及中医药干预研究进展

骨质疏松症（osteoporosis，OP）是一种常见的全身代谢性疾病，是造成骨折的主要原因之一，其发病机制较为复杂，不同原因引起的OP涉及了体内多种代谢途径的紊乱，近年来随着代谢组学在中医药治疗OP过程中的不断研究，发现脂代谢紊乱会抑制骨髓间充质干细胞（bone mesenchymal stemcells，BMSCs）向成骨细胞（osteoblast，OB）增殖分化，促进造血干细胞（stem cell，SC）向破骨细胞（osteoporosis，OC）的分化。其中，脂质异常聚集、炎症反应、氧化应激、氧化脂质、对氧磷酶（paraoxonase，PON）等因素对OB的增殖及分化具有负向调控作用，同时，脂代谢紊乱会使白细胞介素-1（Interleukin-1，IL-1）、白细胞介素-6（interleukin- 6，IL-6）、肿瘤坏死因子（tumor necrosis factor，TNF）等炎症因子的表达上调，产生氧化应激与炎症反应，导致OC分化及增殖和骨吸收加剧。近年来，中医药在预防和治疗OP方面的研究也逐渐增多，其疗效也得到了普遍认可，有诸多研究发现中药有效成分和中药复方可以通过靶向信号分子调控脂代谢的过程来影响OB和OC的分化，在纠正骨代谢失衡方面潜力巨大。因此，通过调控脂代谢相关靶点通路来预防和治疗OP已成为了当下研究热点，现通过对中医药防治OP的作用机制及相关靶点方面的研究进行整理，总结了中医药通过调控脂代谢关键因子来治疗OP的部分机制，旨在为中医药防治OP的深入研究提供参考依据。     

破骨细胞研究新进展

破骨细胞是起源于骨髓单核细胞的多核细胞,成熟的破骨细胞位于骨小梁和骨皮质内表面。骨组织稳态受成骨细胞产生的骨形成和破骨细胞引起的骨吸收之间的平衡调节。然而在病理状态下,多种因素,包括肿瘤坏死因子超家族配体和炎性蛋白质等都促进破骨细胞的形成,使骨代谢失去平衡,导致骨组织过度吸收和过度形成。破骨细胞过度活化常见于骨质疏松症,自身免疫性关节炎等骨代谢疾病。破骨细胞功能障碍同样会导致如石骨症等疾病。因此,破骨细胞是骨代谢疾病预防和治疗方面的重要靶点。随着研究的深入,近年来有关破骨细胞的研究有了新的发现。本文就破骨细胞最新研究进展做一综述。     

High-pressure pulsatile lavage irrigation of fresh intraarticular fractures: effectiveness at removing particulate matter from bone

OBJECTIVE: To determine the effectiveness of high-pressure pulsatile lavage (HPL) versus bulb syringe (BS) irrigation in removing particulate matter from metaphyseal cancellous bone. DESIGN: Four grams of particulate graphite were placed in twenty distal femoral intraarticular osteotomies performed on New Zealand rabbit hind limbs. Two groups of ten specimens were then irrigated using either HPL or BS irrigation. A representative coronal section from each specimen was then prepared for histologic evaluation using 400x light microscopy. The number and distribution of graphite particles-present as small (less than 20 micrometers), medium (20 to 50 micrometers), and large (greater than 50 micrometers) aggregates-were then recorded. RESULTS: The mean maximum perpendicular distance of graphite aggregates of all sizes from the osteotomy site was 12.4 millimeters (+/-SD 2.5) in the HPL group and 12.5 millimeters (+/-SD 2.0) in the BS group (p > 0.5). The mean number of aggregates within four 400x fields (1.08 millimeters) of the osteotomy site was 21.9 (+/-SD 22.0) in the HPL group and 21.8 (+/-SD 27.5) in the BS group (p > 0.5). The mean total number of aggregates in the area surveyed was 129.4 (+/-SD 79.6) in the HPL group and 137.5 (+/-SD 113.6) in the BS group (p > 0.5). Separate analyses controlling for aggregate size of the specimens also revealed no significant differences between HPL and BS irrigation. CONCLUSION: HPL and BS irrigation appear equally effective in removing particulate matter from metaphyseal cancellous bone in an intraarticular fracture model. Furthermore, HPL does not appear to drive particulate matter farther into metaphyseal cancellous bone than BS irrigation.     

不同阶段2型糖尿病诱发骨质疏松症的致病机制研究进展

大量临床研究表明,2型糖尿病(type 2 diabetes mellitus,T2DM)患者的骨折风险明显增加。因此,T2DM诱发的骨质疏松症(osteoporosis,OP)被认为是最严重的糖尿病并发症之一。骨脆性增加是糖尿病性骨质疏松症(diabetic osteoporosis,DOP)的典型特征,其发病机制是多因素引起的,包括肥胖、高胰岛素血症、高血糖(hyperglycemia,HG)、晚期糖基化终产物(advanced glycation end products,AGEs)积聚和氧化产物积累以及微血管病变的存在等。这些因素在T2DM不同时期是相互平衡或相互促进的,而肿瘤坏死因子-α(tumor necrosis factor,TNF-α)、白细胞介素-1(interleukin 1,IL-1)、白细胞介素-6(interleukin 6,IL-6)等炎症因子的异常活化打破了骨形成和骨吸收的代谢平衡,导致骨脆性增加。骨强度和骨折风险的变化取决于疾病进展的阶段。因此,糖尿病骨病的病理生理变化可以通过分别考虑糖尿病早期和晚期骨骼相关因素来广泛讨论,其中早期阶段以胰岛素抵抗和高胰岛素血症为特征,这些因素会导致糖尿病发病和初始阶段的骨密度(bone mineral density,BMD)增加。而晚期阶段的特征是β细胞衰竭,AGEs和氧化产物的堆积,加速衰老和血管并发症的发展。为此,本文希望对T2DM的不同阶段与骨代谢的关系进行综述,以便更好的认识T2DM的进展加速骨脆性风险的病理过程和致病机制,为治疗T2DM和T2DM诱发的OP、降低T2DM患者骨折发生的风险发挥积极的作用。