COVID-19 exacerbates psoriasis progression through inducing IFN-αexpression

As a global public health issue that can cause systemic diseases,COVID-19 inflicts various harms on patients and impacts those with comorbidities.Psoriasis is primarily driven by a subset of T helper cells and the cytokines[1],and microbial infection is a predisposing factor in up to 45%of patients[2].Infection with SARS-CoV-2 may trigger the aggravation of psoriasis.Thus,we conducted a survey to explore the proportion of psoriasis patients who experienced exacerbation and relapse after SARS-CoV-2 infection and also performed a preliminary investigation into the mechanisms involved.One hundred and twenty-four psoriasis patients(79 males and 45 females)who contracted COVID-19 were followed up and provided detailed information.

Cytokine release syndrome triggered by programmed death 1 blockade(sintilimab)therapy in a psoriasis patient:A case report

BACKGROUND In recent years,immune checkpoint inhibitors(ICIs)have demonstrated remarkable efficacy across diverse malignancies.Notably,in patients with advanced gastric cancer,the use of programmed death 1(PD-1)blockade has significantly prolonged overall survival,marking a pivotal advancement comparable to the impact of Herceptin over the past two decades.While the therapeutic benefits of ICIs are evident,the increasing use of immunotherapy has led to an increase in immune-related adverse events.CASE SUMMARY This article presents the case of a patient with advanced gastric cancer and chronic plaque psoriasis.Following sintilimab therapy,the patient developed severe rashes accompanied by cytokine release syndrome(CRS).Fortunately,effective management was achieved through the administration of glucocorticoid,tocilizumab,and acitretin,which resulted in favorable outcomes.CONCLUSION Glucocorticoid and tocilizumab therapy was effective in managing CRS after PD-1 blockade therapy for gastric cancer in a patient with chronic plaque psoriasis.

Apigenin ameliorates imiquimod-induced psoriasis in C57BL/6J mice by inactivating STAT3 and NF-κB

Psoriasis is a chronic autoimmune disease featured by patches on the skin.It is caused by malfunction of immune cells and keratinocytes with inflammation as one of its key features.Apigenin(API)is a natural flavonoid with anti-inflammatory and immunoregulatory properties.Therefore,we speculated that API can ameliorate psoriasis,and determined its effect on the development of psoriasis by using imiquimod(IMQ)-induced psoriasis mouse model.Our results showed that API attenuated IMQ-induced phenotypic changes,such as erythema,scaling and epidermal thickening,and improved splenic hyperplasia.Abnormal differentiation of immune cells was restored in API-treated mice.Mechanistically,we revealed that API is a key regulator of signal transducer activator of transcription 3(STAT3).API regulated immune responses by reducing interleukin-23(IL-23)/STAT3/IL-17A axis.Moreover,it suppressed IMQ-caused cell hyperproliferation by inactivating STAT3 through regulation of extracellular signal-regulated kinase 1/2 and nuclear factor-κB(NF-κB)pathway.Furthermore,API reduced expression of inflammatory cytokines through inactivation of NF-κB.Taken together,our study demonstrates that API can ameliorate psoriasis and may be considered as a strategy for psoriasis treatment.

Causal effect of psoriasis on aortic valve stenosis:a two-sample Mendelian randomization study

Background Epidemiological studies have suggested a potential connection between psoriasis and an increased risk of aortic valve stenosis(AS),though the impact of psoriasis on AS progression remains uncertain.The study aims to investigate the causal relationship between psoriasis and AS using Mendelian randomization(MR)analysis,as well as to uncover potential mechanisms underlying this association.Methods A two-sample MR analysis was conducted using publicly available summary statistics from genome-wide association studies(GWAS)of psoriasis and AS.Cis-eQTL and significant genes were identified for each causal single-nucleotide polymorphisms(SNPs),followed by pathway enrichment and protein-protein interaction(PPI)analysis for functional evaluation.Hub genes were pinpointed by Cytospace.The transcriptional profile of AS population was acquired,and interconnected genes networks were clustered using Molecular Complex Detection(MCODE).Results Our results demonstrate a significant causal relationship between psoriasis and AS,with a genetic predisposition to psoriasis associated with a higher AS risk(odds ratio:1.46).Pathway and PPI analyses unveiled 15 hub genes,including HLA-C,HLA-B,ISG15,IFIT3,and MX2,along with immune-related pathways linking psoriasis and AS.Moreover,the transcriptional profiling of the AS database highlighted the significant involvement of adaptive immune cells in AS development.Notably,among the 15 hub genes,ISG15,MX2,OAS3,OASL,IFI6,and EPSTI1 exhibited higher expression in the AS population.Conclusion Our study provides compelling evidence supporting a causal relationship between psoriasis and AS.Furthermore,the identified hub genes and immune-related pathways may play an important role in the development of both diseases.

Coleus forskohlii shows anti-psoriatic activity in imiquimod-induced psoriasis rats

Objective:To evaluate anti-psoriatic activity of Coleus forskohlii in rats with imiquimod-induced psoriasis.Methods:Imiquimod was used to induce psoriasis in rats.Body weight,skin thickness,erythema,scaling,spleen weight,and histological alternations were measured to assess the effect of Coleus forskohlii.Furthermore,an emulgel formulation containing Coleus forskohlii 10%was prepared and characterized along with its ex vivo permeation studies.Results:The emulgel formulation containing Coleus forskohlii 10%had a pH of 5.40±0.36,with optimum spreadability of(31.67±2.08)g/(cm·s)and viscosity of(15966.67±1274.10)cps,and enhanced both the rate and the extent of drug permeation through psoriatic skin.In an ex vivo study,the quantity of drug permeated(19.18%),deposited(52.38%),and drug remaining in the donor compartments(28.31%)was satisfactory.Coleus forskohlii significantly alleviated imiquimod-induced psoriasis by increasing glutathione and superoxide dismutase activity,decreasing malondialdehyde and nitric oxide levels,and alleviating histological alternations in rat skin.Conclusions:Coleus forskohlii can alleviate imiquimod-induced psoriasis,which may be used as a therapeutic candidate for the treatment of psoriasis.

The Application Progress of Skin Imaging Technology in Psoriasis

Skin imaging technologies such as dermoscopy, high-frequency ultrasound, reflective confocal microscopy and optical coherence tomography are developing rapidly in clinical application. Skin imaging technology can improve clinical diagnosis rate, and its non-invasiveness and repeatability make it occupy an irreplaceable position in clinical diagnosis. With the “booming development” of medical technology, skin imaging technology can improve clinical diagnosis rate. Researchers have made significant advances in assisting clinical diagnosis, prediction, and treatment of disease. This article reviews the application and progress of skin imaging in the diagnosis of psoriasis.

Systemic Amyloidosis Secondary to Psoriasis: A Rare, Autoimmune and Genetically-Determined Disorder That Is Amenable to Treatment with Cyclosporin A—Cyclosporin A for Psoriasis-Induced Amyloidosis

Background: Systemic secondary amyloidosis (SSA) is associated with chronic inflammatory disorders and/or chronic infections. Patients and Methods: Over the past 10 years;a total of 21 patients, with long-term (17 months) and extensive psoriasis (P) with psoriasis area severity index (PASI) >29, were evaluated. Results: Two patients had nephrotic syndrome (proteinuria 3.9 and 3.6 g/day) and decrease creatinine clearance (46 and 62 ml/minute). Their renal biopsy revealed Congo-red (+) nodular glomerulosclerosis that lacked immune-deposits and resisted wash with K-permanganate wash indicating SSA. Three months subsequent to Cyclosporin A (CyA) therapy with 100 mg twice daily;psoriasis improved in all patients with decrease in (PASI) from 29.5 to 3.5 1. In the 2 patients with SSA;proteinuria decreased to 2.1 and 1.8 g/day and creatinine clearance improved to 51 and 69 ml/minute. Such improvement persisted up to 2 years of follow up and up to 78 months in patients with SSA. Conclusion: psoriasis-induced SSA is an autoimmune disease, with genetic predisposition that is amenable to CyA therapy.

Moyamoya syndrome may result from psoriasis: Four case reports

BACKGROUND Moyamoya syndrome(MMS)is a group of diseases that involves more than one underlying disease and is accompanied by moyamoya vascular phenomena.Psoriasis is a chronic immune skin disease closely linked to high blood pressure and heart disease.However,psoriasis-related MMS has not been reported.CASE SUMMARY We collected data on patients with stroke due to MMS between January 2017 and December 2019 and identified four cases of psoriasis.Case histories,imaging,and hematological data were collected.The average age of the initial stroke onset was 58.25±11.52 years;three cases of hemorrhagic and one case of ischemic stroke were included.The average duration from psoriasis confirmation to the initial MMS-mediated stroke onset was 17±3.56 years.All MMS-related stenoses involved the bilateral cerebral arteries:Suzuki grade III in one case,grade IV in two cases,and grade V in one case.Abnormally elevated plasma interleukin-6 levels were observed in four patients.Two patients had abnormally elevated immunoglobulin E levels,and two had thrombocytosis.All four patients received medication instead of surgery.With an average follow-up time of 2 years,two causing transient ischemic attacks occurred in two patients,and no hemorrhagic events occurred.CONCLUSION Psoriasis may be a potential risk factor for MMS.Patients with psoriasis should be screened for MMS when they present with neurological symptoms.

Toll-like receptors 2 polymorphism is associated with psoriasis: A case-control study in the northern Chinese population

Background:Psoriasis is a disease caused by genetics and immune system dysfunction,affecting the skin and joints.Toll-like receptors(TLRs)play an important role in triggering the innate immune response and controlling adaptive immunity.The role of TLR2 in the progression of psoriasis is not well understood.Methods:A case-control study was conducted on a northern Chinese Han population,consisting of psoriasis patients and healthy control subjects.Genotyping was performed using the tetra-primer amplification refractory mutation system-polymerase chain reaction(ARMS-PCR),and allele and genotype frequencies of four SNPs in TLR2 were analyzed in 270 psoriasis patients and 246 healthy controls.Results:Four TLR2 SNPs(rs11938228,rs4696480,rs3804099,rs5743699)were genotyped and found to be in linkage disequilibrium.The genotype distributions of rs11938228 and rs4696480 in two groups were in Hardy-Weinberg equilibrium and statistically significant except for the overdominance model.The haplotypes ATTC and ATCC were found to be protective against psoriasis.Conclusion:Our study found a correlation between TLR2 genetic variations and the likelihood of psoriasis in northern China.

Secoemestrin C Ameliorates Psoriasis-like Skin Inflammation in Mice by Suppressing the TNF-α/NF-κB Signaling Pathway

Objective Secoemestrin C(SC),an epitetrathiodioxopiperazine isolated from Aspergillus nidulans,has been previously reported to have immunomodulatory and hepatoprotective effects against acute autoimmune hepatitis.However,the effect of SC on regulating the inflammation and its underlying mechanisms in the pathogenesis of psoriasis remain unclear.This study aimed to evaluate the effects of SC on inflammatory dermatosis both in vitro and in vivo.Methods In vitro,HaCaT cells were induced with tumor necrosis factor-alpha(TNF-α,10 ng/mL)to establish an inflammatory injury model,and the expression of nuclear transcription factor-κB(NF-κB)pathway components was measured using qRT-PCR and Western blotting.An in vivo mouse model of imiquimod(IMQ)-induced psoriasis-like skin inflammation was used to evaluate the effectiveness of SC in alleviating psoriasis.Results SC significantly blocked the activation of NF-κB signaling in TNF-α-stimulated HaCaT cells.In addition,systemic and local administration of SC improved psoriatic dermatitis in the IMQ-induced mouse model.SC reduced skin scale and significantly inhibited the secretion of inflammatory factors in skin lesions.Conclusion The protective effect of SC against psoriatic-associated inflammation reveals its potential therapeutic value for treating psoriasis.

Medical dilemma:Programmed death 1 blockade(sintilimab)therapy in patients suffering from tumours combined with psoriasis

Tumour immunotherapy represented by immune checkpoint inhibitors(ICIs)has greatly improved the overall prognosis of patients with malignant tumours,and is regarded as an important breakthrough in the field of medicine in recent years.ICIs have gradually become the core of tumour therapy and are increasingly used in the clinic.In order to achieve early clinical prediction and management of immune-related adverse events(irAEs),it is still necessary to perform further research on the mechanisms,risk factors,and predictors of irAE occurrence in the future.Zhou et al describe the consultation of a patient with advanced gastric cancer combined with chronic plaque psoriasis.This case provides an important reference for the use of programmed cell death protein-1(PD-1)inhibitors in patients of tumours combined with chronic plaque psoriasis.This case also highlights that screening of high-risk groups for irAEs is critical before applying PD-1 inhibitors to patients with chronic psoriasis combined with tumours.PD-1 inhibitors are new and potent antineoplastic agents that can cause serious immunerelated adverse events such as toxic epidermal necrolysis release and psoriasis.Glucocorticosteroids are the first-line agents for irAEs.The incidence of rheumatic irAEs may be higher in reality,which will inevitably become a new challenge for rheumatologists and dermatologists.

Cytokine release syndrome induced by anti-programmed death-1 treatment in a psoriasis patient:A dark side of immune checkpoint inhibitors

In recent years,cancer immunotherapy has introduced novel treatments,such as monoclonal antibodies,which have facilitated targeted therapies against tumor cells.Programmed death-1(PD-1)is an immune checkpoint expressed in T cells that regulates the immune system’s activity to prevent over-activation and tissue damage caused by inflammation.However,PD-1 is also expressed in tumor cells and functions as an immune evasion mechanism,making it a therapeutic target to enhance the immune response and eliminate tumor cells.Consequently,immune checkpoint inhibitors(ICIs)have emerged as an option for certain tumor types.Nevertheless,blocking immune checkpoints can lead to immune-related adverse events(irAEs),such as psoriasis and cytokine release syndrome(CRS),as exemp-lified in the clinical case presented by Zhou et al involving a patient with adva-nced gastric cancer who received sintilimab,a monoclonal antibody targeting PD-1.Subsequently,the patient experienced exacerbation of psoriasis and CRS.The objective of this editorial article is to elucidate potential immunologic mechanisms that may contribute to the development of CRS and psoriasis in patients receiving ICIs.It is crucial to acknowledge that while ICIs offer superior safety and efficacy compared to conventional therapies,they can also manifest irAEs affecting the skin,gastrointestinal tract,or respiratory system.In severe cases,these irAEs can lead to life-threatening complications such as circulatory shock or multiorgan failure.Consequently,it is recommended that patients receiving ICIs undergo regular monitoring to identify and manage these adverse events effectively.

Mechanism of traditional Chinese medicine in the treatment of psoriasis with depression:A review

Psoriasis is a kind of immune-mediated, chronic, inflammatory skin disease, which is often associated with different degrees of psychological disorders. Specifically, there is a significant correlation between psoriasis and depression, and they show the relationships of reciprocal causation and mutual promotion. Psoriasis with depression is more harmful than simple psoriasis, and its prognosis is worse, which brings a huge burden to the family and society and is worthy of clinical attention. Based on the pathogenic factors of western medicine and pathogenesis of traditional Chinese medicine in psoriasis with depression, the paper summarized and elaborated the research progress on the mechanism of traditional Chinese medicine in the treatment of psoriasis with depression, in order to provide new ideas for clinical treatment.

金雀异黄素通过调控TGF-β1/Smad3信号通路对2型糖尿病大鼠心肌纤维化的影响

目的 探讨金雀异黄素减轻糖尿病大鼠心肌纤维化的作用及潜在机制。方法 通过高脂饮食结合腹腔注射链脲菌素(STZ)法建立大鼠2型糖尿病(T2DM)模型,并随机分为模型组、二甲双胍组(100 mg/kg)及金雀异黄素低、高剂量组(50、100 mg/kg),另设正常组给予常规饮食,每组10只。各给药组灌胃给药8周,检测体质量、心功能、心脏质量及心脏指数,血清CK-MB、AST及LDH活性,观察心肌纤维化程度,心肌组织转化生长因子-β1(TGF-β1)、Smad同源物3(Smad3)mRNA和蛋白表达,心肌组织Ⅰ型胶原(CollagenⅠ)和Ⅲ型胶原(CollagenⅢ)蛋白分布及表达。结果 与模型组比较,金雀异黄素各剂量组大鼠体质量、每搏输出量(SV)及射血分数(EF)升高(P<0.01),心脏指数、左心室收缩末期内径(LVIDs)、血清肌酸激酶同工酶(CK-MB)、天冬氨酸氨基转移酶(AST)、乳酸脱氢酶(LDH)活性降低(P<0.05,P<0.01),心肌组织胶原相对面积及CollagenⅠ、CollagenⅢ蛋白表达均降低(P<0.05,P<0.01),心肌组织TGF-β1、Smad3 mRNA和蛋白表达降低(P<0.05,P<0.01),金雀异黄素高剂量组左心室舒张末期内径(LVIDd)降低(P<0.05)。结论 金雀异黄素可通过抑制TGF-β1/Smad3信号通路,减轻2型糖尿病大鼠心肌纤维化作用,进而发挥保护心脏效应。

超脉冲二氧化碳点阵激光治疗对凹陷性痤疮瘢痕TGF-β、EGF及bFGF水平变化的影响

目的 研究超脉冲二氧化碳点阵激光治疗对凹陷性痤疮瘢痕转化生长因子-β(TGF-β)、表皮生长因子(EGF)、碱性成纤维细胞生长因子(bFGF)水平变化的影响。方法 选取2020年4月至2022年2月于自贡市第一人民医院就诊的凹陷性痤疮瘢痕患者104例,依据治疗方案分为对照组(n=51,常规手术治疗)和观察组(n=53,超脉冲二氧化碳点阵激光治疗)。比较两组临床疗效、皮肤情况、血管内皮因子(TGF-β、EGF、bFGF)水平、复发及不良反应发生率。结果 观察组临床总有效率(84.91%)高于对照组(62.75%),差异有统计学意义(P<0.05)。治疗后,两组紫质、纹理、色素斑、毛孔评分均下降,且观察组上述评分均比对照组低,差异有统计学意义(P<0.05)。治疗后,观察组TGF-β、bFGF水平比对照组高,EGF水平比对照组低,差异有统计学意义(P<0.05)。观察组复发率比对照组低,差异有统计学意义(P<0.05)。观察组不良反应总发生率(19.61%)比对照组低(5.66%),差异有统计学意义(P<0.05)。结论 应用超脉冲二氧化碳点阵激光治疗凹陷性痤疮瘢痕患者疗效显著,可有效改善瘢痕组织中的TGF-β、EGF、bFGF表达水平,安全性良好。

虎杖苷通过抑制TGF-β/Smad信号通路改善动脉粥样硬化大鼠动脉粥样硬化斑块和内皮炎症反应

目的:探讨虎杖苷通过抑制转化生长因子β(TGF-β)/Smad信号通路对动脉粥样硬化(AS)大鼠AS斑块和内皮炎症反应的改善作用。方法:将60只大鼠随机分成空白对照组、模型对照组、虎杖苷低、中、高剂量组和阳性对照组,每组10只。正常对照组大鼠用普通饲料喂养,其余各组大鼠采用高脂饲料喂养与维生素D3腹腔注射联合的方法制备AS大鼠模型。虎杖苷低、中、高剂量组大鼠每天灌胃虎杖苷40、80、160 mg/kg,阳性对照组大鼠每天灌胃辛伐他汀5 mg/kg,模型对照组和空白对照组大鼠每天灌胃等量生理盐水。给药结束后,油红O染色观察大鼠主动脉AS斑块形成情况;全自动生化分析仪检测大鼠三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)水平;酶联免疫吸附法检测大鼠血清中肿瘤坏死因子(TNF)-α、IL-6、IL-8、C反应蛋白(CRP)、单核细胞趋化蛋白1(MCP-1)、同型半胱氨酸(Hcy)、细胞间黏附分子1(ICAM-1)、内皮素-1(ET-1)含量;蛋白免疫印迹法检测大鼠TGF-β1、Smad2/3、p-Smad2/3蛋白表达水平。结果:与空白对照组相比,模型对照组大鼠主动脉内壁出现大量AS斑块,血清中TG、TC、LDL-C水平及TNF-α、IL-6、IL-8、CRP、MCP-1、Hcy、ICAM、ET-1含量明显升高,HDL-C水平明显降低,主动脉组织中TGF-β1蛋白表达、p-Smad2/3/Smad2/3显著升高(P<0.05)。虎杖苷干预后AS大鼠主动脉内壁斑块面积明显减小,血清中TG、TC、LDL-C水平及TNF-α、IL-6、IL-8、CRP、MCP-1、Hcy、ICAM、ET-1含量显著降低,HDL-C水平显著升高,主动脉组织中TGF-β1蛋白表达、p-Smad2/3/Smad2/3明显减小(P<0.05),以上指标变化均呈剂量依赖性(P<0.05)。阳性对照组TC、LDL-C、HDL-C水平与虎杖苷高剂量组无明显差异(P>0.05),其余指标均比虎杖苷高剂量组更低(P<0.05)。结论:虎杖苷通过调节血脂、降低细胞炎症因子的表达,从而减少AS斑块的形成,改善AS大鼠体内的炎症反应,其机制与抑制TGF-β/Smad信号通路激活有关。

基于TGF-β/BMP/Smad信号通路治疗激素性股骨头坏死中医药研究进展

激素性股骨头坏死(steroid-induced osteonecrosis of the femoral head,SIONFH)是由于糖皮质激素使用不当或过度而引起的髋关节疾病,发病机制尚未统一,临床疗效亦不佳。当前,没有效果明确的药物可以延缓疾病进程,而中医药治疗SIONFH在临床上取得一定疗效。即便如此,仍未能完整的从分子生物及细胞生物学角度阐明中药治疗SIONFH的作用机制。转化生长因子-β(TGF-β)/骨形态发生蛋白(BMP)/Smad信号通路的转导是防治SIONFH的研究热点之一,故该文阐明了该信号通路的转导机制以及与SIONFH的联系,检索了基于该通路治疗SIONFH的全部中药及复方并阐述其影响机制。基于中医对SIONFH的认识,现临床上使用补肝肾强筋骨以及活血祛瘀通络类的方药治疗SIONFH,且具有良好的疗效。中药通过调控该通路,可刺激骨髓间充质干细胞成骨分化,降低破骨细胞含量,减少脂肪生成,改善微循环,抗氧化损伤,促进股骨头内血管新生,从而促进股骨头损伤的修复。现基于TGF-β/BMP/Smad信号通路对中医药治疗SIONFH的研究进展做一综述,期许为中医药治疗SIONFH提供理论依据及参考。

益气养阴通络汤联合贝那普利治疗糖尿病肾病疗效及对血清TGF-β1、VEGF指标影响

目的探讨益气养阴通络汤联合贝那普利治疗糖尿病肾病(diabetic nephropathy,DN)的疗效及对转化生长因子-β_(1)(transforming growth factor-β_(1),TGF-β_(1)),血管内皮生长因子(vascular endothelial growth factor,VEGF)影响。方法选取2019年10月—2021年10月医院收治的DN病人94例,随机分为对照组(n=48)和观察组(n=46)。入院后两组病人均实施生活方式相关的指导,包括体质量控制、运动、戒烟酒等,给予脂质的代谢紊乱相关纠正、血糖控制、血压等基础的治疗,对照组实施盐酸贝那普利片的口服治疗,观察组则在此基础上实施益气养阴通络汤治疗,两组持续治疗4周。对比两组临床疗效、尿微量白蛋白(microalbumin,mALB)、尿白蛋白肌酐比(urine albumin creatine ratio,UACR)、β_(2)微球蛋白(β_(2)-microglobulin,β_(2)-MG)水平、中医证候评分、血清同型半胱氨酸(homocysteine,Hcy)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-6(Interleukin-6,IL-6)、血清TGF-β_(1)和VEGF及空腹血糖(fasting plasma glucose/fasting blood glucose,FPG)、餐后2 h血糖(2 hour postprandial blood glucose,2 h PG)和糖化血红蛋白(glyeosylated hemoglobin,HbAlc)指标变化。结果治疗前两组mALB、UACR、β_(2)-MG指标间无统计学意义(P>0.05);治疗后两组mALB、UACR、β_(2)-MG指标较治疗前显著降低(P<0.05);并且观察组降低较明显(P<0.05);观察组治疗总有效率较对照组明显较高(P<0.05);治疗后两组主症评分、次症评分和中医证候总评分明显降低(P<0.05);且观察组降低较明显(P<0.05);治疗后两组血清Hcy、TNF-α、IL-6指标明显降低(P<0.05);且观察组降低较明显(P<0.05);治疗后两组血清TGF-β_(1)和VEGF指标较治疗前明显降低(P<0.05);且观察组降低较明显(P<0.05);治疗后两组FPG、2 h PG和HbAlc指标较治疗前明显降低(P<0.05);且观察组降低较明显(P<0.05)。结论采用益气养阴通络汤联合贝那普利治疗DN具有较好的临床疗效,可降低血清TGF-β_(1),VEGF指标,降低蛋白尿水平。

基于miRNA21-5p调控TGF-β1/Smads信号通路探讨苓桂气化方抗射血分数保留心力衰竭心肌纤维化的机制

目的基于miRNA21-5p调控转化生长因子-β1(transforming growth factor beta 1,TGF-β1)/Smads信号通路探讨苓桂气化方抗射血分数保留心力衰竭(heart failure with preserved ejection fraction,HFpEF)心肌纤维化的机制。方法40只4周龄自发性高血压大鼠(spontaneously hypertensive rats,SHR)平均分为HFpEF组、沙库巴曲缬沙坦组(LCZ696,0.018 g·kg^(-1))、苓桂气化方低剂量组(LGQH-L,3.87 g·kg^(-1))和苓桂气化方高剂量组(LGQH-H,7.74 g·kg^(-1)),给予高脂、高盐及高糖饮食16周及腹腔注射链脲霉素溶液8周建立HFpEF大鼠模型。10只威斯塔京都(Wistar Kyoto,WKY)大鼠和10只SHR大鼠作为对照组,以普通饲料喂养至实验结束。造模成功后,WKY、SHR和HFpEF组给予等剂量生理盐水,其他3组按照预先规定的干预措施,每天灌胃1次,持续6周。干预结束后,行超声心动图测量左心室(left ventricle,LV)前壁厚度(LV end-diastolic anterior wall thickness,LVAWd)、LV后壁厚度(LV end-diastolic posterior wall thickness,LVPWd)、LV舒张末内径(LV end-diastolic internal diameter,LVIDd)、LV射血分数(LV ejection fraction,LVEF)、LV舒张早期二尖瓣流入峰值速度(E)、舒张晚期二尖瓣流入峰值速度(A)和LV舒张早期二尖瓣环运动速度(e'),并计算E/A和E/e';酶联免疫吸附试验检测血清心房钠尿肽(atrial natriuretic peptide,ANP)、B型利钠肽(B-type brain natriuretic peptide,BNP)及半乳糖凝集素3(Galectin-3,Gal-3);病理切片进行苏木精伊红及马松染色观察心肌肥厚及纤维化,并计算LV室壁厚度(LV wall thickness,LVWT)、胶原体积分数(collagen volume fraction,CVF)及血管周围纤维化比率(perivascular fibrosis ratio,PFR);实时定量聚合酶链反应检测LV心肌miRNA21-5p及TGF-β1/Smads信号通路相关mRNA表达;蛋白印迹检测LV心肌TGF-β1/Smads信号通路相关蛋白表达。结果与对照组比较,HFpEF组的LVAWd、LVPWd、LVIDd、E/A、E/e'、ANP、BNP、Gal-3、LVWT、CVF和PFR显著升高(P<0.05或P<0.01);LV心肌miR-NA21-5,α-SMA、CollⅠ、CollⅢ、TGF-β1、Smad2、Smad3 mRNA表达和α-SMA、CollⅠ、CollⅢ、TGF-β1、P-Smad2/3蛋白表达显著上调(P<0.05或P<0.01);Smad7 mRNA及蛋白表达显著下调(P<0.05或P<0.01)。与HFpEF组比较,苓桂气化方呈剂量依赖性减少LVAWd、LVPWd、LVIDd、E/A、E/e'、ANP、BNP、Gal-3、LVWT、CVF和PFR(P<0.05或P<0.01);下调miRNA21-5p,α-SMA、CollⅠ、CollⅢ、TGF-β1、Smad2、Smad3 mRNA表达和α-SMA、CollⅠ、GF-β1、P-Smad2/3蛋白表达(P<0.05或P<0.01);上调Smad7 mRNA及蛋白表达(P<0.05或P<0.01)。结论苓桂气化方可能通过靶向miRNA21-5p调控TGF-β1/Smads信号通路抑制心肌纤维化,从而减轻HFpEF大鼠LV重塑和舒张功能障碍,是治疗HFpEF的有效中药复方。

脂联素干预对宫腔粘连大鼠子宫内膜组织中NLRP3、TGF-β1和Smad2表达的影响

目的:探讨脂联素干预对宫腔粘连大鼠子宫内膜组织中NLRP3、TGF-β1和Smad2表达的影响。方法:健康雌性SD大鼠24只采用双重损伤法建立宫腔粘连模型后,随机平均分为模型组(腹腔注射生理盐水1 mL/d)和脂联素组[腹腔注射脂联素蛋白10μg/(kg·d)+生理盐水1 mL/d],连续干预14 d;12只未造模大鼠为正常对照组。末次给药后,麻醉大鼠,收取子宫组织,HE染色及Masson染色法检测子宫内膜腺体数量和纤维化面积百分比,免疫组化、Western blot及RT-qPCR法检测NLRP3、TGF-β1及Smad2蛋白和mRNA的表达。结果:正常对照组、模型组和脂联素组子宫内膜腺体数分别为(55.1±5.6)、(13.8±4.5)和(33.7±7.8),纤维化面积百分比分别为(5.39±0.65)%、(65.18±1.92)%和(38.16±1.91)%;与正常对照组比较,模型组腺体数减少,纤维化面积百分比增加(P<0.05);与模型组比较,脂联素组腺体数增加,纤维化面积百分比减少(P<0.05)。模型组和脂联素组子宫内膜组织中NLRP3、TGF-β1和Smad2蛋白和mRNA的表达均高于正常对照组(P<0.05);脂联素组低于模型组(P<0.05)。结论:脂联素可能通过抑制NLRP3炎症小体的激活和TGF-β1/Smad2信号通路,减轻宫腔粘连大鼠子宫内膜炎症,从而抑制纤维化进展。