吡非尼酮对新西兰兔膝关节创伤后瘢痕挛缩的改善作用

 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。

Pirfenidone improves scar contracture of the knee joint after seawater immersion in rabbits

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.