吡非尼酮治疗特发性肺纤维化的临床效果观察

目的探讨吡非尼酮治疗特发性肺纤维化的临床效果。方法本研究选取2016年8月-2018年5月丹东市某医院收治的60例特发性肺纤维化患者为研究对象。采用随机数字表法将患者分为对照组与观察组,每组30例。对照组患者给予醋酸泼尼松口服治疗,观察组患者在对照组治疗基础上服用吡非尼酮治疗。比较2组患者治疗前及治疗16周时的最大呼气流量(PEF)、第1秒用力呼气容积(FEV1)、用力肺活量(FVC)、动脉血氧分压(PaO2)及白介素-6(IL-6)水平;比较治疗16周时2组患者的不良反应发生情况。结果治疗后,观察组患者PEF,FEV1及FVC分别为(3.58±0.22)L/s,(1.97±0.20)L及(1.99±0.10)L,大于对照组的(3.02±0.17)L/s,(1.77±0.23)L及(1.76±0.26)L,且2组患者PEF,FEV1及FVC均大于治疗前,差异均有统计学意义(P<0.05)。治疗后,观察组患者PaO2为(65.58±7.17)mmHg(1 mmHg=0.133 kPa),高于对照组的(59.49±6.84)mmHg,且2组患者PaO2均高于治疗前,差异均有统计学意义(P<0.05)。治疗后,观察组患者IL-6水平为(13.77±1.62)pg/mL,低于对照组的(15.30±1.53)pg/mL,且2组患者IL-6水平均低于治疗前,差异均有统计学意义(P<0.05)。2组患者不良反应发生率均较低,且差异无统计学意义(P>0.05)。结论采用吡非尼酮联合醋酸泼尼松治疗特发性肺纤维化的临床效果显著,其可有效改善患者的肺功能,降低IL-6水平,并提高PaO2水平,安全可靠,值得临床推广应用。     

吡菲尼酮的抗氧化能力及其对大鼠油酸性急性肺损伤的防护作用

目的探讨新型抗炎药物吡菲尼酮(PFD)对大鼠油酸(OA)性急性呼吸窘迫综合征(ARDS)的氧化-抗氧化的影响。方法129只SD大鼠,分为正常对照组、油酸组和3个不同剂量的PFD干预组(20、40、80mg/kg灌胃);根据取材观察时间每组又分为0.5、1、2、6、24h5个亚组。动态观察PFD对氧自由基生成酶[如NADPH氧化酶、黄嘌呤氧化酶(XO)和髓过氧化物酶(MPO)等]及清除氧自由基物质如谷胱甘肽过氧化物酶(GSH-Px)活力和总抗氧化能力(TAC)的作用。结果PFD可降低OA性ARDS大鼠肺组织的自由基含量和氧自由基生成酶(如NADPH氧化酶、XO和MPO等)活力;同时可增强肺组织中GSH-Px活力和TAC。结论PFD对OA性ARDS具有早期干预作用,主要是抑制产生自由基的酶类尤其是NADPH氧化酶活力,从而达到避免自由基直接损伤肺组织的目的。     

吡非尼酮和尼达尼布抑制博来霉素诱导的小鼠肺纤维化药效比较

目的:比较不同时期给予吡非尼酮和尼达尼布对博来霉素诱导的小鼠肺纤维化的作用。方法:根据给药时间和给药时长,建立5类小鼠模型:炎症时期给药模型、纤维化早期预防给药模型、纤维化早期治疗模型、纤维化晚期治疗模型和全程给药模型,分别检测炎症指标和纤维化指标。结果:(1)抗炎抗氧化评估:吡非尼酮和尼达尼布均能降低炎症细胞数目,抑制炎症因子分泌。吡非尼酮对白细胞介素1β(IL-1β)和IL-4的抑制效果较好(P<0.01),尼达尼布对IL-6、IFN-γ的抑制作用较好(P<0.05)。吡非尼酮可显著提高超氧化物歧化酶(SOD)活性(P<0.01),而尼达尼布可显著降低丙二醛(MDA)和髓过氧化物酶(MPO)含量(P<0.01)。(2)肺组织胶原含量检测:在纤维化早期治疗模型、纤维化晚期治疗模型、全程给药模型中,尼达尼布对羟脯氨酸的抑制作用均优于吡非尼酮(P<0.05)。而吡非尼酮在纤维化早期预防给药模型中对羟脯氨酸的抑制作用较好(P<0.01)。(3)肺组织病理学评价:吡非尼酮和尼达尼布均可减少肺组织炎症浸润和纤维化面积,抑制效果对比结果同胶原检测结果一致。结论...     

吡非尼酮对大鼠矽肺纤维化的抑制作用

目的 探讨吡非尼酮(PFD)对大鼠矽肺纤维化的抑制作用.方法 75只SD雄性大鼠,随机分成未处理对照组、生理盐水组、生理盐水+PFD组、SiO2组、SiO2+PFD组,每组15只,采用非暴露式气管内染尘法,SiO2组和SiO2+PFD组注入SiO2粉尘悬液(25 mg/ml),生理盐水组和生理盐水+PFD组注入等量生理盐水,染尘后第2天灌胃给予PFD(50 mg/kg),分别观察7、21、42 d后处死.HE、VG和Foot染色观察肺组织的病理形态学改变并进行病理分级,测定肺组织中羟脯氨酸(HYP)的含量.结果 大鼠肺组织病理观察显示,SiO2+PFD组肺组织纤维化程度比同期SiO2组明显减轻,胶原纤维形成缓慢,矽结节分级评分降低.第42天时,SiO2+PFD组大鼠肺组织HYP含量[(0.75±0.12)mg/g肺组织]比SiO2组[(1.19±0.17)mg/g肺组织]明显降低,差异有统计学意义(P＜0.05).结论 PFD能降低大鼠矽肺纤维化程度并减少肺组织中HYP的含量,对实验性大鼠矽肺纤维化具有抑制作用.     

吡非尼酮联合尼达尼布对特发性肺纤维化治疗的作用

〔摘 要〕 目的：探讨吡非尼酮联合尼达尼布对特发性肺纤维化的治疗效果。 方法：将 2019 年 1 月至 2022 年 5 月 安阳市人民医院收治的 100 例特发性肺纤维化患者随机分为两组,每组 50 例。对照组患者在治疗时应用吡非尼酮, 观察组患者在治疗时应用吡非尼酮联合尼达尼布,比较两组患者的治疗总有效率、不良反应发生率、血清炎症因子指 标、血管内皮功能指标、肺通气功能指标、肺纤维化评分、生活质量评分。 结果：与对照组相比,观察组患者的治疗 总有效率更高,差异具有统计学意义（P ＜ 0.05）。在治疗后,与对照组比较,观察组患者中各项血清炎症因子指标、 血管内皮素 –1、肺纤维化评分均更低,观察组患者中内皮源性一氧化氮、第 1 秒用力呼气量（FEV1）、FEV1/ 肺活 量（FVC）、生活质量评分均更高,差异均具有统计学意义（P ＜ 0.05）。两组患者不良反应发生率比较,差异无统 计学意义（P ＞ 0.05）。 结论：动态 颅内压监测应用于HICH术后,能够提高后续治疗中药物应用的合理性,降低术后并发症发生风险,辅助患者改善预后。     

Idiopathic pulmonary fibrosis: Molecular mechanisms and potential treatment approaches

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive disease with high mortality that commonly occurs in middle-aged and older adults. IPF, characterized by a decline in lung function, often manifests as exertional dyspnea and cough. Symptoms result from a fibrotic process driven by alveolar epithelial cells that leads to increased migration, proliferation, and differentiation of lung fibroblasts. Ultimately, the differentiation of fibroblasts into myofibroblasts, which synthesize excessive amounts of extracellular matrix proteins, destroys the lung architecture. However, the factors that induce the fibrotic process are unclear. Diagnosis can be a difficult process; the gold standard for diagnosis is the multidisciplinary conference. Practical biomarkers are needed to improve diagnostic and prognostic accuracy. High-resolution computed tomography typically shows interstitial pneumonia with basal and peripheral honeycombing. Gas exchange and diffusion capacity are impaired. Treatments are limited, although the anti-fibrotic drugs pirfenidone and nintedanib can slow the progression of the disease. Lung transplantation is often contraindicated because of age and comorbidities, but it improves survival when successful. The incidence and prevalence of IPF has been increasing and there is an urgent need for improved therapies. This review covers the detailed cellular and molecular mechanisms underlying IPF progression as well as current treatments and cutting-edge research into new therapeutic targets.     

Pirfenidone Prevents Capsular Contracture After Mammary Implantation

Background Pirfenidone (PFD), a new antifibrotic and antiinflammatory agent, prevents and resolves fibrous tissue. This study evaluated the effect of PFD on adverse events in mammary implants using an animal model. Mammary implantation, the most frequent aesthetic surgery, may present several complications after surgery such as swelling, capsule contracture, hardness, and pain. Methods Wistar rats underwent submammary implantation with either smooth or textured silicone gel implants and were administrated 200 mg/kg of PFD daily. The control group received saline. The animals were killed at 8 weeks. The capsular tissue of both implants was removed for histologic and molecular analyses. Results Typical postaugmentation periimplant capsules with opacity on adjacent tissues developed 8 weeks after silicone implantation. No significant differences were observed between the textured and smooth implants in any analyzed parameter. Clearly, PFD reduced capsule thickness around submmamary tissue, fibroblast-like cell proliferation, and recruitment of inflammatory cells. The total cell numbers per field were reduced as well. In contrast, the control group presented abundant mononuclear cell infiltration and fibroblast-like cell proliferation. The total content of collagen in the PFD group was 50% less than in the control group. Fibroblast cells displayed 45% less activated phenotype in the PFD group than in the control group, as determined by immunohistochemistry techniques. In the PFD animals, transforming growth factor-β (TGF-β) decreased 85% and collagen 1 gene expression 60%, compared with the control group. Conclusion The findings show a positive effect of PFD on mammary contracture in 10 rats. Despite the small number of animals, the differences found in 10 control rats encourage the authors to propose a larger study later and to suggest PFD as a potential preventive strategy in human mammary implantation surgery. Presented at the Latinoamerican meeting on plastic surgery. Buenos Aires, Argentina, April 2006.     

Influence of pirfenidone on airway hyperresponsiveness and inflammation in a Brown-Norway rat model of asthma

Pirfenidone was administered to sensitized Brown Norway rats prior to a series of ovalbumin challenges. Airway hyperresponsiveness, inflammatory cell infiltration, mucin and collagen content, and the degree of epithelium and smooth muscle staining for TGF-beta were examined in control, sensitized, and sensitized/challenged rats fed a normal diet or pirfenidone diet. Pirfenidone had no effect on airway hyperresponsiveness, but reduced distal bronchiolar cell infiltration and proximal and distal mucin content. Statistical analysis showed that the control group and sensitized/challenged pirfenidone diet group TGF-beta staining intensity scores were not significantly different from isotype controls, but that the staining intensity scores for the sensitized/challenged normal diet group was significantly different from isotype controls. These results suggest that pirfenidone treatment is effective in reducing some of the components of acute inflammation induced by allergen challenge.