Mechanisms of the alternative activation of macrophages and non-coding RNAs in the development of radiation-induced lung fibrosis

Radiation-induced lung fibrosis(RILF) is a common side effect of thoracic irradiation therapy and leads to high mortality rates after cancer treatment. Radiation injury induces inflammatory M1 macrophage polarization leading to radiation pneumonitis, the first stage of RILF progression. Fibrosis occurs due to the transition of M1 macrophages to the anti-inflammatory pro-fibrotic M2 phenotype, and the resulting imbalance of macrophage regulated inflammatory signaling. Non-coding RNA signaling has been shown to play a large role in the regulation of the M2 mediated signaling pathways that are associated with the development and progression of fibrosis. While many studies show the link between M2 macrophages and fibrosis, there are only a few that explore their distinct role and the regulation of their signaling by non-coding RNA in RILF. In this review we summarize the current body of knowledge describing the roles of M2 macrophages in RILF, with an emphasis on the expression and functions of non-coding RNAs.

Cetirizine regulates scleroderma skin fibrosis in mice via the TGF-β1/Smad3 signaling pathway

Objective:To investigate the effect of cetirizine on the fibrosis of skin tissue in systemic sclerosis(SSc)mice and its mechanism of action.Methods:Thirty-two BALB/C mice were randomly divided into a blank group,a model group,a cetirizine low-dose group,and a cetirizine high-dose group,with eight in each group.The blank group was injected with normal saline on the back,and the other three groups were injected with bleomycin on the back to prepare SSc mouse models.The mice were injected once a day for 28 consecutive days,while the normal group and the model group were given saline.The dose group was administrated intragastrically at 2 mg/kg and 5 mg/kg,respectively,for 28 consecutive days.Detect the thickness of the dermis by taking the skin tissue in the back injection area of each group.Hematoxylin-eosin staining(HE)and Masson staining.Sample hydrolysis method to detect hydroxyproline(HYP)content in skin tissue.Immunohistochemical detection ofα-smooth muscle actin(α-SMA)expression in skin tissues.Enzyme-linked immunosorbent assay(ELISA)to detect serum interleukin(IL-6,IL-10)and transforming growth factor(TGF-αand TGF-β1).Quantitative real-time PCR(qRT-PCR)was used to detect the expression levels of collagen type I(COL1A1),type III collagen(COL3A1),Smad homolog 3(Smad3),and TGF-β1 mRNA.Western blot was used to detect the expression levels of COL1A1,COL3A1 and p-Smad3.Results:Compared with the blank group,the dermis thickness and HYP content of the model group increased,the skin tissue lesions and fibrosis were more severe,theα-SMA positive expression intensity in the skin tissue was higher,and the serum IL-6,IL-10,TGF-α,TGF-β1 content increased,COL1A1,COL3A1,Smad3,TGF-β1 mRNA expression levels increased in skin tissues,COL1A1,COL3A1,p-Smad3 protein expression increased,the differences were statistically significant(P<0.05).Compared with the model group,the dermal thickness and HYP content of the low and high dose cetirizine groups were reduced,the degree of skin tissue lesions and fibrosis was improved,the expression ofα-SMA in skin tissues was weakened,the levels of IL-6,IL-10,TGF-α,TGF-β1 in serum were reduced,the expression levels of COL1A1,COL3A1,Smad3 and TGF-β1 in skin tissues were reduced,and the expression levels of COL1A1,COL3A1,and p-Smad3 proteins were reduced,the decrease in the high-dose group was more significant,and the differences were statistically significant(P<0.05).Conclusion:Cetirizine can improve the degree of fibrosis of skin tissue in SSc mice and reduce the immune inflammation response.The mechanism of action is related to the TGF-β1/Smad3 signaling pathway.

Tacrolimus may play a role in dermatitis and radiation-induced skin injury through cellular senescence

Skin Exposure of skin to ionizing radiation can induce acute or chronic biological effects,resulting in radiation-induced skin injury(RSI).Premature cellular senescence,caused by oxidative stress and/or DNA damage from chemical or physical agents,leads to the decrease of cellular proliferation and physiological function.Persistent DNA damage and accumulation of senescent cells are associated with the progression of radiation-induced injury.Atopic dermatitis and RSI have similar inflammatory symptoms.The treatment of tacrolimus(TAC)in atopic dermatitis may be associated with premature cellular senescence.TAC can prevent the onset of cellular senes-cence by inactivating the p38 mitogen-activated protein kinase(p38 MAPK).The activation of p38 MAPK can induce the senescence-associated secretory phenotype(SASP)by enhancing the transcriptional activity of nuclear factor kappa-B(NF-κB),which ultimately leads to premature cellular senescence.FK506 binding protein 51(FKBP51)exhibits resistance to ionizing radiation,but the mechanism of TAC regulation of ionizing radiation-induced premature senescence still needs further study.This review discusses the mechanism of cellular senes-cence in RSI and the role of TAC in both dermatitis and RSI.

Understanding how MSCs reverse radiation-induced fibrosis:HGF vs.TGF-B1

Radiation induced fibrosis(RIF)can be understood as a form of chronic radiation-induced bystander effect(RIBE).It is a fibrotic process different than acute radiation syndrome(ARS),which is an inflammatory process that has different mediators and effector cells.It is triggered by Reactive Oxygen Species(ROS)activation of the matrixembedded L-TGF-βcomplex.TGF-βacts by directing cellular processes that culminate in a fibrotic state.These include epithelial and endothelial mesenchymal transition(EMT and EnMT),G1 phase growth arrest,stimulation of fibrosis,and apoptosis,characterized by hypocellularity with a predominance of fibrocytes and myofibroblasts,fibrosis,and variable loss of tissue function.Fat grafting is the only clinically available tool to reverse RIF.The reversal of RIF is mediated by the mesenchymal stem cells(MSCs)embedded in the stromal vascular fraction(SVF)adipose tissue.The mechanism of action is the release of HGF(hepatocyte growth factor)by the MSCs into the surrounding RIF tissue.The HGF initiates a“mitotic growth program”that reprograms cell behavior.These changes include EMT and EnMT,stimulation of cell proliferation and morphogenesis,anti-apoptosis,downregulation of TGF-β,dissolution of fibrosis,and cell motility.The“mitotic growth program”culminates in tissue regeneration and reversal of RIF.

圣草酚对TGF-β1诱导的人皮肤成纤维细胞增殖、氧化应激反应及TGF-β1/Smad信号通路活化的影响

目的 探讨圣草酚对转化生长因子β1(TGF-β1)诱导的人皮肤成纤维细胞(HSF)的增殖、氧化应激反应及TGF-β1/Smad信号通路活化的影响。方法 将HSF分为对照组、模型组、圣草酚低剂量组、圣草酚中剂量组、圣草酚高剂量组、SB-431542组。对照组不做任何处理,模型组用5.0 ng/mL TGF-β1干预24 h,圣草酚低剂量组、圣草酚中剂量组、圣草酚高剂量组分别用40μmol/L、80μmol/L、160μmol/L圣草酚和5.0 ng/mL TGF-β1同时干预24 h,SB-431542组用10μmol/L SB-431542和5.0 ng/mL TGF-β1同时干预24 h。检测各组HSF细胞活力、α平滑肌肌动蛋白(α-SMA)蛋白表达水平、活性氧簇(ROS)含量、超氧化物歧化酶(SOD)活性,TGF-β1、α-SMA、Ⅰ型胶原蛋白(ColⅠ)、Ⅲ型胶原蛋白(Co lⅢ)、基质金属蛋白酶2(MMP2)的mRNA表达量及TGF-β1的蛋白表达水平。检测对照组、模型组、圣草酚中剂量组HSF的Smad2、Smad3、磷酸化Smad2 (p-Smad2)、磷酸化Smad3 (p-Smad3)蛋白表达水平。结果 与对照组相比,模型组的HSF细胞活力及α-SMA蛋白表达水平增加,ROS含量增加而SOD活性降低,TGF-β1、α-SMA、ColⅠ、Co lⅢ和MMP2 mRNA表达量上调,TGF-β1、Smad2、Smad3、p-Smad2、p-Smad3的蛋白表达量亦上调(P<0.05)。与模型组相比,圣草酚各剂量组和SB-431542组HSF细胞活力降低、ROS含量降低、SOD活性增强,且α-SMA、ColⅠ、Co lⅢ、MMP2的mRNA表达量和TGF-β1蛋白表达量下调,圣草酚中剂量组、圣草酚高剂量组和SB-431542组HSF细胞中α-SMA蛋白表达水平降低,圣草酚中剂量组及SB-431542组Smad2、Smad3、p-Smad2、p-Smad3蛋白表达量下调(P<0.05)。圣草酚低剂量组、圣草酚中剂量组、圣草酚高剂量组HSF细胞活力、α-SMA蛋白表达水平、ROS含量依次降低,SOD活性依次增强,α-SMA、ColⅠ、Co lⅢmRNA表达量依次降低(P<0.05)。结论 圣草酚可能通过抑制氧化应激反应及TGF-β1/Smad通路的活化,从而剂量依赖性地抑制TGF-β1诱导的HSF细胞纤维化。

基于TGF‐β1/Smads信号通路探讨红花抗硬皮病小鼠皮肤纤维化的作用机制

目的探讨红花抗硬皮病小鼠皮肤纤维化的作用及对转化生长因子β1(TGF-β1)/Smads信号通路的影响。方法将64只雌性BALB/c小鼠分为对照组(16只)、模型组(16只)、泼尼松组(8只)、红花前干预组(16只)和红花后干预组(8只)。除对照组外,其他4组小鼠采用皮下注射博来霉素诱导硬皮病小鼠模型。造模当天给予泼尼松组小鼠灌胃0.45 mg/mL醋酸泼尼松混悬液,给予红花前干预组小鼠灌胃0.15 g/mL红花水提液,给予对照组、模型组小鼠灌胃生理盐水,造模第15天给予红花后干预组小鼠灌胃0.15 g/mL红花水提液,以上各组小鼠均连续灌胃4周(0.2 mL/d)。干预4周后,观察各组小鼠皮肤外观变化及皮肤病理组织学改变,比较各组小鼠的真皮厚度,采用免疫组化法检测各组小鼠皮肤组织Ⅰ型胶原蛋白(COLⅠ)、α-平滑肌肌动蛋白(α-SMA)的蛋白表达水平,采用实时荧光定量PCR检测各组小鼠皮肤组织COLⅠ-a1、COLⅠ-a2、α-SMA、TGF-β1、Smad2、Smad3的mRNA表达水平,采用Western blot检测各组小鼠皮肤组织TGF-β1、Smad2、Smad3、磷酸化Smad2、磷酸化Smad3的蛋白表达情况。结果(1)模型组小鼠背部未见新生毛发,皮肤硬化明显、有粘连,不易被提起,真皮厚度增厚,各药物干预组皮肤症状较模型组改善,真皮厚度变薄,以泼尼松组、红花前干预组改善最明显。(2)与对照组比较,模型组小鼠皮肤组织COLⅠ、α-SMA的蛋白表达水平,以及COLⅠ-a1、COLⅠ-a2、α-SMA的mRNA表达水平升高(P<0.05);与模型组比较,红花前干预组、红花后干预组和泼尼松组小鼠皮肤组织COLⅠ、α-SMA的蛋白表达水平,以及COLⅠ-a1、COLⅠ-a2、α-SMA的mRNA表达水平下降,且泼尼松组、红花前干预组小鼠皮肤组织COLⅠ、α-SMA的蛋白表达水平低于红花后干预组,红花前干预组小鼠皮肤组织COLⅠ-a1、COLⅠ-a2的mRNA表达水平低于红花后干预组(P<0.05)。(3)与对照组比较,模型组小鼠皮肤组织TGF-β1、Smad2、Smad3的蛋白及mRNA,以及磷酸化Smad2、磷酸化Smad3的蛋白表达水平升高,红花前干预组小鼠皮肤组织TGF-β1、Smad3的mRNA表达水平降低,Smad2的mRNA表达水平升高(P<0.05);与模型组比较,红花前干预组小鼠皮肤组织TGF-β1、Smad2、Smad3的蛋白及mRNA,以及磷酸化Smad2、磷酸化Smad3的蛋白表达水平降低(P<0.05)。结论红花可以抑制肌成纤维细胞的激活,减少细胞外基质的生成与堆积,从而发挥抗硬皮病小鼠皮肤纤维化的作用,其机制可能与下调硬皮病小鼠皮肤组织TGF-β1/Smads信号通路相关蛋白的表达有关。

病理性瘢痕形成的细胞分子机制的研究进展

皮肤损伤在愈合后会形成纤维化组织,即瘢痕。其中的病理性瘢痕因其外观不佳及痛痒不适感,严重影响患者的生活质量。然而,目前病理性瘢痕的发病机制尚不完全明确,缺乏有效的动物模型及临床根治手段。本文回顾总结了病理性瘢痕免疫微环境中的细胞分子学机制与相互作用,旨在为病理性瘢痕诊断标志物与治疗靶点的研发以及组织工程构建的优化提供参考。

Understanding wound healing in obesity

Obesity has become more prevalent in the global population.It is associated with the development of several diseases including diabetes mellitus,coronary heart disease,and metabolic syndrome.There are a multitude of factors impacted by obesity that may contribute to poor wound healing outcomes.With millions worldwide classified as obese,it is imperative to understand wound healing in these patients.Despite advances in the understanding of wound healing in both healthy and diabetic populations,much is unknown about wound healing in obese patients.This review examines the impact of obesity on wound healing and several animal models that may be used to broaden our understanding in this area.As a growing portion of the population identifies as obese,understanding the underlying mechanisms and how to overcome poor wound healing is of the utmost importance.

皮肤纤维化疾病中肌成纤维细胞来源的研究进展

典型的皮肤纤维化疾病包括增生性瘢痕、瘢痕疙瘩、硬皮病等。该类疾病以肌成纤维细胞过度激活和细胞外基质沉积为特征,可导致永久性瘢痕和器官功能损伤,严重影响患者身心健康。肌成纤维细胞在皮肤纤维化疾病中起到了核心作用。目前研究表明,成纤维细胞、内皮细胞、周细胞、巨噬细胞等细胞可在经历促纤维化的介质等多因素的诱导、皮肤纤维化相关信号通路的激活、形态学和生化特征的改变、α-平滑肌肌动蛋白(α-SMA)等肌成纤维细胞标记物的表达等过程后,转化为肌成纤维细胞。靶向这些细胞转化的过程有望成为调控皮肤纤维化疾病进展的新治疗策略。本文重点围绕皮肤纤维化疾病中肌成纤维细胞来源的相关进展作一综述。

CircTUBD1 Regulates Radiation-induced Liver Fibrosis Response via a circTUBD1/micro-203a-3p/Smad3 Positive Feedback Loop

Background and Aims: Radiation-induced liver fibrosis (RILF), delayed damage to the liver (post-irradiation) re-mains a major challenge for the radiotherapy of liver ma-lignancies. This study investigated the potential function and mechanism of circTUBD1 in the development of RILF. Methods: By using a dual luciferase assay, RNA pull- down assays, RNA sequencing, chromatin immunoprecipi-tation (known as ChIP) assays, and a series of gain- or loss-of-function experiments, it was found that circTUBD1 regulated the activation and fibrosis response of LX-2 cells induced by irradiation via a circTUBD1/micro-203a-3p/ Smad3 positive feedback loop in a 3D system. Results: Knockdown of circTUBD1 not only reduced the expression of α-SMA, as a marker of LX-2 cell activation, but also significantly decreased the levels of hepatic fibrosis mol-ecules, collagen type I alpha 1 (COL1A1), collagen type III alpha 1 (COL3A1), and connective tissue growth factor (CTGF) in a three-dimensional (3D) culture system and RILF model in vivo. Notably, knockdown of circTUBD1 al-leviated early liver fibrosis induced by irradiation in mice models. Conclusions: This study is the first to reveal the mechanism and role of circTUBD1 in RILF via a circTUBD1/ micro-203a-3p/Smad3 feedback loop, which provides a novel therapeutic strategy for relieving the progression of RILF.

Prevention and treatment for radiation-induced skin injury during radiotherapy

The skin tissue has the largest area in the human body and functions as both a barrier and a defender.As such,it tends to be the first tissue to be damaged.Advances in medical technology provide prospects as well as side effects,for example,radiation therapy for cancer.With increasing cancer morbidity and radiation widely applied for cancer therapy,radiation-induced skin injury(RSI)has become a serious concern.In recent decades,research efforts have focused on the mechanisms underlying RSI.This review summarizes the mainstream opinions on these mechanisms,including the pathological,molecular biological,and cytobiological alterations.Radiationinduced reactive oxygen species(ROS),cytokines and involved signaling pathways are evaluated.Other relevant aspects include radiation-induced skin fibrosis(RSF)and radiation-related skin cell senescence.Moreover,we review strategies for the prevention and treatment in clinical and pre-clinical studies to support the treatment of RSI during radiotherapy.The prevention strategies include dose control,pre-irradiation instructions,and RSI assessments,while the main treatments include physical therapy,external-use dressings or creams,biological therapy and surgical reconstruction.

博来霉素诱导不同小鼠模型观察“肺主皮毛”理论的实验研究

目的博来霉素(BLM)分别诱导系统性硬化症(SSc)小鼠模型及肺纤维化小鼠模型,观察两种模型皮肤及肺的病理改变及羟脯氨酸(HYP)含量变化,为“肺主皮毛”理论提供实验依据。方法分别建立SSc小鼠模型和肺纤维化小鼠模型,两种模型分别设置注射BLM模型组和注射生理盐水对照组。取每组相应皮肤和肺脏,进行HE染色和HYP含量检测。结果系统性硬化症模型和肺纤维化模型小鼠的肺组织和表皮均出现明显病理改变,且HYP含量在两种小鼠动物模型皮肤和肺组织中均明显升高(P<0.05)。结论博来霉素诱导的系统性硬化症小鼠模型及肺纤维化小鼠模型都能够同时产生肺和皮肤病变,从中医角度分析,这是“肺主皮毛”的具体体现。

miR-2116-3p在人增生性瘢痕中的表达及作用

背景:目前多项研究证实了miRNA影响增生性瘢痕的发生发展,Ⅰ型胶原与增生性瘢痕成纤维细胞密切相关,猜测miR-2116-3p也有可能与增生性瘢痕的发生发展有关系。目的:探讨miR-2116-3p在人增生性瘢痕中的表达及作用。方法:收集新疆医科大学第一附属医院6例患者的增生性瘢痕组织与6例患者重睑术后正常皮肤组织,采用qRT-PCR法检测miR-2116-3p与Ⅰ型胶原的表达。取增生性瘢痕组织,原代培养第3-6代成纤维细胞,分为阴性对照组、miR-2116-3p模拟物组和miR-2116-3p抑制物组,分别转染对应的序列,用CCK-8法与EdU试剂盒检测细胞增殖活力,划痕实验检测细胞迁移能力,流式细胞术检测细胞凋亡,qRT-PCR法与Western blot法检测Ⅰ型胶原、Ⅲ型胶原和α平滑肌肌动蛋白的基因与蛋白表达,双荧光素酶实验验证其靶向结合。结果与结论:(1)增生性瘢痕组织中miR-2116-3p的mRNA表达量低于正常皮肤组织(P<0.01),Ⅰ型胶原的mRNA表达量低于正常皮肤组织(P<0.01);(2)转染后24,48,72 h,与阴性对照组比较,miR-2116-3p模拟物组细胞活力降低(P<0.05或P<0.01),miR-2116-3p抑制物组细胞活力升高(P<0.05或P<0.01);转染后48 h,与阴性对照组比较,miR-2116-3p模拟物组细胞EdU标记数减少(P<0.01),miR-2116-3p抑制物组EdU标记数增加(P<0.05);(3)转染后24 h,与阴性对照组比较,miR-2116-3p模拟物组细胞划痕面积、细胞凋亡率增加(P<0.01),miR-2116-3p抑制物组细胞划痕面积、细胞凋亡率减少(P<0.01或P<0.05);(4)转染后24h,与阴性对照组比较,miR-2116-3p模拟物组Ⅰ型胶原、Ⅲ型胶原和α-平滑肌肌动蛋白的基因与蛋白表达下降(P<0.05或P<0.01),miR-2116-3p抑制物组Ⅰ型胶原、Ⅲ型胶原和α-平滑肌肌动蛋白的蛋白表达升高(P<0.01);(5)双荧光素酶实验显示,miR-2116-3p能够与Ⅰ型胶原靶向结合;(6)结果表明,人增生性瘢痕中miR-2116-3p表达下调,miR-2116-3p可能通过靶向抑制Ⅰ型胶原的表达抑制人增生性瘢痕成纤维细胞的增殖、迁移,促进其凋亡。

瘢痕疙瘩病理机制研究进展

瘢痕疙瘩是一种皮肤纤维增生性疾病,病理实质是过度纤维化引起的创面过度愈合。其病理机制错综复杂且尚不明确。目前认为,瘢痕疙瘩细胞机制方面主要涉及炎症细胞和纤维化相关细胞,以及生长因子、白细胞介素、肿瘤坏死因子、基质金属蛋白酶等细胞因子;分子机制主要涉及TGF-β/Smad通路、NF-κB通路、STAT3信号通路、MAPK信号通路、黏着斑激酶等分子机制。该文从细胞、细胞因子和分子信号通路多个角度就瘢痕疙瘩病理机制的最新研究进展做一综述。

β-catenin activation in hair follicle dermal stem cells in duces ectopic hair outgrowth and skin fibrosis

Hair follicle dermal sheath(DS)harbors hair follicle dermal stem cells(hfDSCs),which can be recruited to replenish DS and dermal papilla(DP).Cultured DS cells can differentiate into various cell lineages in vitro.However,it is unclear how its plasticity is modulated in vivo.Wnt/β-catenin signaling plays an important role in maintaining stem cells of various lineages and is required for HF development and regeneration.Here we report that activation ofβ-catenin in DS generates ectopic HF outgrowth(EF)by reprogramming HF epidermal cells and DS cells themselves,and endows DS cells with hair inducing ability.Epidermal homeostasis of pre-existing HFs is disrupted.Additionally,cell-autonomous progressive skin fibrosis is prominent in dermis,where the excessive fibroblasts largely originate from DS.Gene expression analysis of purified DS cells with activatedβ-catenin revealed significantly increased expression of Bmp,Fgf,and Notch ligands and administration of Bmp,Fgf,or Notch signaling inhibitor attenuates EF formation.In summary,our findings advance the current knowledge of high plasticity of DS cells and provide an insight into understanding how Wnt/β-catenin signaling controls DS cell behaviors.

PPAR-γ与纤维化疾病关系研究进展

纤维化疾病是临床上常见的疾病,至今仍是一个治疗难题。近年来的研究发现,过氧化物酶体增殖物激活受体(PPARs)中PPAR-γ亚型的活化或激动剂在器官纤维化的发生过程中有调节作用,可减缓纤维化进程。本文就PPAR-γ与肝、肾、肺、心肌、眼及皮肤等器官纤维化发病关系的研究现状与进展做一综述。

类获得性免疫缺陷(阴性HIV)“患者”的流行病学调查

目的对社区类获得性免疫缺陷(AIDS)综合征(阴性HIV)"患者"进行病因探索。方法采用定性系统分析筛检国内外相关综合征报道病例,探索类AIDS综合征"患者"临床特征可能的聚类属性;通过现况调查掌握"患者"人群的一般特征和临床特征。结果定性系统分析显示,目前在世界范围,与类AIDS综合征(阴性HIV)"患者"相似的疾病有2种,即CD4+T淋巴细胞缺陷综合征(ICL)和非结核分枝杆菌感染(NTM感染);通过174例网络调查和52例现场观察,发现"患者"人群以男性为主,青、中年为主;在国内分布地区广泛;主诉症状涉及呼吸道、消化道、皮肤、肌肉、骨骼和神经系统;根据症状特点,病程有急性期和稳定期之分;群体症状及体征为:淋巴结部位肿胀感、骨痛、肌肉"跳"(痛)、淋巴结节、皮肤结节(皮疹)、舌苔白厚、关节弹响、皮肤干燥;52例"患者"检测发现CD4+T淋巴细胞<500/μL 17例(32.69%)、CD4/CD8比值异常16例(30.77%)、干扰素-γ抗体阳性17例(36.69%)和PPD阳性39例(++～+++,75.00%);高危险性行为是可疑的暴露因素之一。结论类AIDS综合征(阴性HIV)"患者"现象不能完全用心理因素予以解释,其呈现的临床特征有明显的一致性和规律性,亟待开展深入研究进行分析。

红花水煎液内服对硬皮病小鼠皮肤RORγt表达的影响

目的:观察红花水煎液对硬皮病小鼠皮肤RORγt表达的影响,探讨红花抗SSc皮肤纤维化的免疫机制。方法:将32只BALB/C小鼠随机分为空白对照组、模型对照组、醋酸泼尼松组、红花组,每组8只。除空白对照组外,其余3组注射博来霉素缓冲液诱导硬皮病模型,同时予生理盐水(空白对照组和模型对照组)、醋酸泼尼松(醋酸泼尼松组)、红花水煎液(红花组)灌胃处理28 d。取小鼠皮肤,苏木素-伊红染色测真皮厚度及评价皮肤炎症程度;免疫组化法、蛋白质印迹法检测皮肤RORγt的蛋白表达水平。结果:各造模组小鼠皮肤均有不同程度增厚,炎性细胞浸润,炎症评分、RORγt蛋白表达均不同程度升高,与空白对照组比较,差异有统计学意义(P<0.05)。与模型对照组比较,醋酸泼尼松组和红花组小鼠真皮厚度及皮肤炎症评分、RORγt蛋白表达下降,差异均有统计学意义(P<0.05)。与醋酸泼尼松组比较,红花组真皮厚度降低,差异有统计学意义(P<0.05),皮肤炎症评分及RORγt蛋白表达差异无统计学意义(P>0.05)。结论:红花水煎液能降低硬皮病小鼠皮肤RORγt蛋白表达,抑制免疫炎症反应而具有抗皮肤纤维化的治疗作用。

曲尼司特新的治疗作用及其作用机制的研究进展

曲尼司特 (tranilast)作为一种抗变态反应药 ,可以稳定肥大细胞和嗜碱粒细胞的细胞膜 ,抑制过敏性物质释放。近年来发现其与转化生长因子 β(TGF β)、血小板源性生长因子 (PDGF)、单核细胞趋化蛋白 1(MCP 1)等细胞因子有密切关系 ,可抑制脏器纤维化、动脉粥样硬化等。本文就曲尼司特的新的治疗作用及其可能的作用机制做一综述。

系统性硬皮病多器官受累超声评估研究进展

系统性硬皮病是多器官受累的系统性疾病,采用影像方法评估其结构受损程度对于早期诊断、及时治疗及定期随访十分必要。综述常规超声及弹性超声在系统性硬皮病(如皮肤厚度与硬度、骨肌病变、肺间质纤维化及微血管病变)评估中的潜在应用价值及其超声表现,归纳总结了超声对系统性硬皮病多器官受累的不同评估价值的最新进展。