目的 探讨口服吡非尼酮(Pirfenidone,PFN)对海水浸泡膝关节创伤后瘢痕挛缩的影响。方法 按照随机数字表法,将20只新西兰兔随机分为4组(n=5):生理盐水对照组(NS组),无菌海水对照组(SW组),生理盐水+吡非尼酮治疗组(NS+PFN组),无菌海水+吡非尼酮治疗组(SW+PFN组)。吡非尼酮治疗组给予每日口服0.75 g吡非尼酮(混于饲料中),对照组仅给予饲料。4周后观察切口愈合情况,处死动物后采集瘢痕组织进行Masson染色,采集标本进行ELISA检测羟脯氨酸含量和转化生长因子β1(TGF-β1)含量。结果 术后各组动物切口愈合良好。吡非尼酮治疗后,Masson染色结果显示,切口瘢痕胶原纤维分布相对稀疏,大致呈平行排列,表现相对更为规则。检测结果显示,在SW组、NS组、SW+PFN组和NS+PFN组,羟脯氨酸分别为(114.20±14.54)ng/ml、(99.21±18.27)ng/ml、(87.91±12.02)ng/ml和(76.17±18.72)ng/ml。SW+PFN组羟脯氨酸水平明显低于SW组,差异具有统计学意义(P<0.05)。进一步检测显示,SW组和SW+PFN组TGF-β1水平分别为(151.53±20.21)ng/ml和(106.53±12.86)ng/ml,SW+PFN组TGF-β1水平明显低于SW组,差异具有统计学意义(P<0.05)。结论 吡非尼酮可以缓解海水浸泡膝关节创伤后关节周围瘢痕性挛缩,改善关节功能障碍,其作用机制可能与抑制胶原蛋白合成及下调TGF-β1水平有关。
Abstract
Objective To investigate the effect of oral administration of Pirfenidone (PFN) on scar contracture of the knee joint after seawater immersion.Methods According to the random-number-table method, 20 rabbits were randomly divided into four groups (n=5): normal saline control group (NS group), seawater control group (SW group), normal saline+PFN treatment group (NS+PFN group), and seawater+PFN treatment group (SW+PFN group). Animals in the PFN treatment groups were given 0.75 g of PFN daily (within normal feedstuffs), while animals in the control groups were given normal feedstuffs only. After 4 weeks, the animals were killed, and the suprapatellar bursa was collected for Masson staining. The content of hydroxyproline and TGF-β1 were detected by ELISA. Results The incision healed well. After Pirfenidone treatment, Masson staining results showed that collagen fibers of incision scar were relatively sparse, roughly parallel arrangement, and the performance was relatively regular. The results showed that the levels of hydroxyproline were (114.20±14.54) ng/ml, (99.21±18.27) ng/ml, (87.91±12.02) ng/ml and (76.17±18.72) ng/ml in SW group, NS group, SW+PFN group and NS+PFN group, respectively. The level of hydroxyproline in SW+PFN group was significantly lower than that in SW group (P<0.05). Further detection showed that the levels of TGF-β1 in SW group and SW+PFN group were (151.53±20.21) ng/ml and (106.53±12.86) ng/ml, respectively. The level of TGF-β1 in SW+PFN group was significantly lower than that in SW group (P<0.05). Conclusions Pirfenidone can alleviate the scar contracture around the knee joint after seawater immersion and improve the joint dysfunction. The mechanism underlying may be related to the inhibition of collagen synthesis and the down-regulation of TGF-β1 level.
关键词
吡非尼酮 /
膝关节 /
瘢痕挛缩 /
海水浸泡
Key words
pirfenidone /
knee joint /
scar contracture /
seawater immersion
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] Martinotti S, Bucekova M, Majtan J, et al. Honey: an effective regenerative medicine product in wound management [J]. Curr Med Chem, 2019, 26 (27): 5230-5240.
[2] Garcia L P, Huang A, Corlew D S, et al. Factors affecting burn contracture outcome in developing countries: a review of 2506 patients [J]. Ann Plast Surg, 2016, 77 (3): 290-296.
[3] Chen H, Tao J, Wang J, et al. Artesunate prevents knee intraarticular adhesion via PRKR-like ER kinase (PERK) signal pathway [J]. J Orthop Surg Res, 2019, 14 (1): 448.
[4] Ai J G, Zhao F, Gao Z M, et al. Treatment of seawater immersion-complicated open-knee joint fracture [J]. Genet Mol Res, 2014, 13 (3): 5523-5533.
[5] Jin J, Togo S, Kadoya K, et al. Pirfenidone attenuates lung fibrotic fibroblast responses to transforming growth factor-beta1 [J]. Respir Res, 2019, 20 (1): 119.
[6] Chen L, Davison S W, Selimovic E A, et al. Load-power relationships for high-speed knee extension exercise [J]. J Strength Cond Res, 2019, 33 (6): 1480-1487.
[7] Kaneguchi A, Ozawa J, Kawamata S, et al. Development of arthrogenic joint contracture as a result of pathological changes in remobilized rat knees [J]. J Orthop Res, 2017, 35 (7): 1414-1423.
[8] Riaz H M, Mehmood Bhatti Z. Quality of life in adults with lower limb burn injury [J]. J Burn Care Res, 2020, 41 (6): 1212-1215.
[9] 李 文, 曾国庆, 陈爱宝, 等. 兔膝关节开放性海水浸泡损伤模型的构建 [J]. 海南医学, 2017, 28 (2): 183-185.
[10] 洪建明, 刘 敏, 胡学峰. 海水浸泡感染后皮肤软组织缺损修复的差异性观察 [J]. 中国矫形外科杂志, 2013, 21 (15): 1569-1571.
[11] Tottoli E M, Dorati R, Genta I, et al. Skin wound healing process and new emerging technologies for skin wound care and regeneration [J]. Pharmaceutics, 2020, 12 (8): 1-30.
[12] 胡骁骅,覃凤均,李 娟,等. 穿支皮瓣整复严重烧伤患者四肢大关节部位瘢痕增生挛缩畸形的效果[J]. 中华烧伤杂志, 2019, 35 (6): 417-422.
[13] Fang X, Hu X, Zheng Z, et al. Smad interacting protein 1 influences transforming growth factor-beta1/Smad signaling in extracellular matrix protein production and hypertrophic scar formation [J]. J Mol Histol, 2019, 50 (6): 503-514.
[14] Wei G, Xu Q, Liu L, et al. LY2109761 reduces TGF-beta1-induced collagen production and contraction in hypertrophic scar fibroblasts [J]. Arch Dermatol Res, 2018, 310 (8): 615-623.
[15] Shi K, Wang F, Xia J, et al. Pirfenidone inhibits epidural scar fibroblast proliferation and differentiation by regulating TGF-beta1-induced Smad-dependent and-independent pathways [J]. Am J Transl Res, 2019, 11 (3): 1593-1604.
[16] Ruwanpura S M, Thomas B J, Bardin P G. Pirfenidone: molecular mechanisms and potential clinical applications in lung disease [J]. Am J Resp Cell Mol, 2020, 62 (4): 413-422.
[17] 王晓英, 孙志东, 王 蕾, 等. 腹部开放性海水浸泡伤BALB/c小鼠模型的建立 [J]. 军事医学, 2019, 43 (2): 122-125.
[18] Chen H, Tao J, Wang J, et al. Artesunate prevents knee intraarticular adhesion via PRKR-like ER kinase (PERK) signal pathway [J]. J Orthop Surg Res, 2019, 14(1): 1-10.
基金
国家自然科学基金(81501896);福建省自然科学基金(2018J01338)
PDF(1093 KB)
