Pirfenidone increases the epithelialization rate of skin graft donor sites

Background

Improving epithelialization of donor sites of split-thickness skin grafts (STSG) is extremely important in burned patients. We aimed to assess the efficacy of pirfenidone, a drug with anti-inflammatory, antifibrotic, and antioxidant effects, to accelerate wound healing. We hypothesized that pirfenidone accelerates the epithelialization rates in donor sites.

CT analysis of the effect of pirfenidone in patients with idiopathic pulmonary fibrosis

Purpose

Pirfenidone is a new, anti-fibrotic drug used for the treatment of idiopathic pulmonary fibrosis (IPF). The aim of this study was to evaluate the utility of computed tomography (CT) in the imaging assessment of the response to pirfenidone therapy.

Materials and methods

Subjects were 78 patients with IPF who underwent CT on two occasions with one-year interval (38 consecutive patients treated with pirfenidone and 40 age-matched control). Changes in the fibrous lesion on sequential CTs were assessed as visual score by two radiologists. We measured the volume and change per year of fibrous pattern (F-pattern) quantitatively using a computer-aided system on sequential CTs.

Results

The baseline vital capacity (%pred VC) was 74.0 ± 14.0% in the pirfenidone group and 74.6 ± 16.6% in controls (p = NS). Deterioration of respiratory status was defined as 10% or greater decline in %pred VC value after 12-month treatment. A significantly larger proportion of pirfenidone-treated patients showed stable respiratory status (21 of 38, 65.6%) than the control (15 of 40, 37.5%). The change in fibrous lesion was significantly smaller in the pirfenidone group than the control in both of visual score (p = 0.006) and computer analysis (p < 0.001). The decline in VC correlated significantly with the increase in fibrotic lesion (p < 0.001).

Conclusion

CT can be used to assess pirfenidone-induced slowing of progression of pulmonary fibrosis.     

吡非尼酮对实验性大鼠肝纤维化的作用

目的研究吡非尼酮（PFD）对实验性大鼠的抗肝纤维化作用。方法45只雄性Wistar大鼠随机均分为3组。模型组腹腔注射1%二甲基亚硝胺（DMN）10?mg/(kg·d),每周连续3d,共4周,制作肝纤维化模型;干预组除应用DMN外,同时给予PFD 500?mg/(kg·d)灌胃,1次/d,共4周;模型组及正常组以等体积生理盐水灌胃作对照。4周试验结束时进行组织学检查、电镜观察、血清肝纤维化指标、肝功能及转化生长因子 β1（TGF β1）检测。结果与模型组相比,干预组大鼠体质量下降较少(P＜0.05)、肝脾肿大较轻（P＜0.05）,血清透明质酸、层粘连蛋白和Ⅳ型胶原浓度均明显低于模型组（P＜0.05）;干预组血清谷丙转氨酶、谷草转氨酶、总胆红素及TGF β1含量与模型组相比明显降低（P＜0.001）;MASSON染色显示,干预组肝脏纤维化及炎症反应明显减轻,无明显假小叶;透射电镜观察证实干预组大鼠肝细胞损伤明显减轻,肝窦及Disse腔内胶原纤维沉积明显减少。结论PFD对实验性大鼠肝纤维化模型具有明显的抗肝纤维化作用,其机制可能与抑制TGF β1的产生有关,PFD有可能用于肝脏疾病的抗纤维化治疗。     

吡非尼酮对大鼠坐骨神经损伤后瘢痕形成及功能恢复的实验研究

目的探讨大鼠坐骨神经损伤后细胞因子抑制剂吡非尼酮对神经吻合口处瘢痕形成及神经功能恢复的影响。方法选用健康雄性SD大鼠60只,制作右侧坐骨神经损伤模型,术后随机分为3组,分别为对照组、低剂量组和高剂量组,每组20只,分别给予0 mg/kg、25 mg/kg、100 mg/kg吡非尼酮混悬液灌胃。术后于第4、12周分别行坐骨神经功能指数、神经电生理测定,然后取材进行Ⅰ型胶原蛋白免疫组织化学染色,最终对实验结果进行图像分析和统计学处理。结果坐骨神经功能指数:术后第4周,三组之间两两比较,差异无统计学意义(P0.05);术后第12周,低剂量组优于对照组(P0.01),高剂量组优于低剂量组(P0.01);神经电生理:术后第4周,三组之间神经传导速度、潜伏期、波幅两两比较,差异无统计学意义(P0.05);术后第12周,与对照组相比,低剂量组和高剂量组神经传导速度显著增快(P0.05),潜伏期缩短(P0.05),波幅升高(P0.05),且高剂量组优于低剂量组(P0.05);Ⅰ型胶原蛋白沉积量:术后第4周,与对照组相比,低剂量组和高剂量组神经吻合口处Ⅰ型胶原蛋白沉积量明显减少(P0.01),低剂量组与高剂量组相比,差异无统计学意义(P0.05);术后第12周,与对照组相比,低剂量组和高剂量组神经吻合口处Ⅰ型胶原蛋白沉积量明显减少(P0.01),且高剂量组比低剂量组减少更明显(P0.05)。结论吡非尼酮能明显减少神经吻合口处Ⅰ型胶原蛋白沉积,有效抑制瘢痕形成,促进神经功能恢复。     

Pirfenidone; can it be a new horizon for the treatment of pulmonary fibrosis in mustard gas-intoxicated patients?

Sulfur mustard is an alkylating substance still regarded as a threat in chemical warfare and terrorism. Lung parenchymal damage occurs in the most severe inhalational exposures. It accompanies an increased risk of respiratory tract carcinomas and chronic respiratory sequelae including chronic bronchitis, bronchiectasis, pulmonary fibrosis, interstitial lung disease, emphysema, and bronchiolitis obliterans. Pirfenidone is an antifibrotic with anti-inflammatory and anti hydroxyl radical activities which stabilizes pulmonary function in idiopathic pulmonary fibrosis patients. It can be suggested in chronically exposed soldiers or workers with signs and symptoms of pulmonary fibrosis to improve their quality of life and even prognosis.     

中药方剂抗肺纤维化方治疗肺纤维化患者的临床研究

〔摘 要〕 目的：研究中药方剂抗肺纤维化方治疗肺纤维化（PF）患者的疗效。方法：选取福建中医药大学附属第二人民医院 2020 年 3 月至 2021 年 10 月期间收治的 70 例 PF 患者,采用随机数字表法分为对照组与观察组,各35 例。对照组患者采用常规西药治疗,观察组患者在常规西药治疗基础上采用中药方剂抗肺纤维化方治疗。比较两组患者的临床疗效、治疗前及治疗 3 个月后中医证候积分、肺功能指标、肺纤维化指标、圣乔治呼吸疾病问卷（SGRQ）、高分辨计算机断层扫描（HRCT）评分。结果：观察组患者治疗总有效率为 88.67 %,高于对照组的 62.86 %,差异具有统计学意义（P ＜ 0.05）。治疗后观察组患者的乏力、呼吸气短、自汗、咳嗽评分均低于对照组,差异具有统计学意义（P ＜ 0.05）。治疗后观察组患者的第 1 秒用力呼气容积（FEV1）、用力肺活量（FVC）、最大呼气流量（PEF）均高于对照组,差异具有统计学意义（P ＜ 0.05）。治疗后观察组患者的透明质酸（HA）、层粘连蛋白（LN）、Ⅲ型胶原（Ⅲ –Col）均低于对照组,差异具有统计学意义（P ＜ 0.05）。治疗后观察组患者的 SGRQ、HRCT 评分均低于对照组,差异具有统计学意义（P ＜ 0.05）。结论：采用中药方剂抗肺纤维化方与常规西药联合治疗 PF 患者,能进一步改善患者临床症状,降低肺纤维化程度,增强肺功能,提高临床疗效。     

吡菲尼酮对牛血清蛋白诱导的肝纤维化大鼠肝损害的保护作用观察

目的探讨吡菲尼酮对牛血清蛋白诱导的大鼠肝纤维化的影响。方法雄性Wistar大鼠30只被随机分为3组,给予模型组腹腔注射牛血清白蛋白,正常对照组接受等量的生理盐水腹腔注射,治疗组在腹腔注射牛血清白蛋白5 w后,按200 mg·kg-1·d-1灌胃给药吡菲尼酮,治疗4 w后处死试验动物,留取肝脏组织,行HE和Masson染色,观察肝脏病理学改变,采用免疫组化法检测Smad6蛋白表达。结果与模型组比,吡菲尼酮治疗组肝组织纤维化S3和S4期病变较模型组明显减少,炎症细胞浸润明显减少,胶原纤维间隔缩小,着色变浅;模型组肝组织Smad6相对表达量为(108.2±33.6),显著低于吡菲尼酮治疗组[(329.4±39.2),P0.05]。结论吡菲尼酮可抑制牛血清蛋白诱导的大鼠肝纤维化,其机制与通过上调Smad 6蛋白表达有关。     

吡非尼酮及盐酸氨溴索对百草枯诱导的大鼠急性肺损伤保护作用的比较

目的比较吡非尼酮（pirfenidone,PF）及盐酸氨溴索（ambroxol hydrochloride,AH）对百草枯（paraquat,PQ）诱导的大鼠急性肺损伤的保护作用。方法40只雄性成年SD大鼠随机分为正常对照组、PQ组、PQ＋PF组、PQ＋AH组,采用腹腔注射20％PQ溶液诱导大鼠急性PQ中毒模型。苏木精伊红（HE）染色评价肺组织损伤情况;测定肺组织湿重／干重比（W／D）;测定各组大鼠肺组织中超氧化物歧化酶（SOD）活性、丙二醛（MDA）、谷胱甘肽（GSH）含量变化;ELISA法检测血清中肿瘤坏死因子a（TNF-a）及白细胞介素（IL-6）含量。结果与正常对照组大鼠相比,PQ组大鼠肺组织肺泡萎缩,部分过度膨胀,组织炎性侵润和纤维化明显,肺组织氧化应激水平明显升高,肺组织W／D增加,血浆中TNF-a及IL-6含量增加;与PQ组相比,给予PF或AH治疗后大鼠肺组织损伤和纤维化降低,大鼠肺组织氧化应激水平降低,肺组织W／D降低,血浆中TNFa及IL-6含量降低。PF与AH组相比,各指标差异无统计学意义。结论PF和AH均可以减轻PQ中毒大鼠肺组织损伤,其治疗作用可能与其抗炎抗氧化有关。