Department of Physiology, Faculty of Medicine, Pamukkale University, Denizli, Turkey.
Department of Orthopedics and Traumatology, Denizli State Hospital, Denizli, Turkey.
Clin Rheumatol. 2023 Dec;42(12):3361-3373. doi: 10.1007/s10067-023-06767-6. Epub 2023 Sep 21.
This study investigated the efficacy of sericin in treating experimental Achilles tendinopathy (AT) in rats via the transforming growth factor-beta (TGF-β)/mothers against decapentaplegic (Smad) pathway compared with diclofenac sodium (DS).
An AT model was induced in rats using collagenase enzyme type I and divided into 5 groups: C (control), AT (diseased control), ATS (AT treated with sericin), ATN (AT treated with DS), and ATSN (AT treated with sericin and DS). Sericin injection was given on the 3 and 6 days by intratendinous injection (0.8 g/kg/mL), and DS was administered for 14 days by oral gavage (1.1 mg/kg/day). Serum concentrations of total oxidant-antioxidant status (TOS-TAS), TGF-β1, decorin, Smad2, and connective tissue growth factor (CTGF) were measured. Histopathologic and immunohistochemical (IHC) studies were conducted on Achilles tendon samples.
The TOS, oxidative stress index (OSI), TGF-β1, Smad2, CTGF, and decorin serum concentrations were significantly higher in AT than in C and significantly lower in ATS than in AT (P<0.05). Histopathological examination revealed that irregular fibers, degeneration, and round cell nuclei were significantly elevated in AT. Spindle-shaped fibers were similar to those in C, and degeneration was reduced in ATS. TGF-β1 and Smad2/3 expression was increased, and collagen type I alpha-1 (Col1A1) expression was decreased in AT vs. C (P=0.001). In the ATS, TGF-β1 and Smad2/3 expression decreased, and Col1A1 expression increased. The Bonar score significantly increased in the AT group (P =0.001) and significantly decreased in the ATS group (P =0.027).
Sericin shows potential efficacy in reducing oxidative stress and modulating the TGF-β/Smad pathway in experimental AT models in rats. It may be a promising therapeutic agent for AT, warranting further clinical studies for validation. Key Points • This study revealed that sericin mitigates AT-induced damage through the TGF-β/Smad pathway in an AT rat model. • ELISA and IHC investigations corroborated the effectiveness of sericin via the pivotal TGF-β/Smad pathway in tissue repair. • Evidence indicates that sericin enhances collagen synthesis,shapes tendon fiber structure, and diminishes histopathological degeneration. • Sericin's antioxidant properties were reaffirmed in its AT treatment application.
本研究通过转化生长因子-β（TGF-β）/Smads 途径比较丝胶与双氯芬酸钠（DS）治疗实验性跟腱病（AT）的疗效。
采用 I 型胶原酶酶诱导大鼠 AT 模型，分为 5 组：C（对照组）、AT（患病对照组）、ATS（丝胶治疗 AT）、ATN（DS 治疗 AT）和 ATSN（丝胶和 DS 联合治疗 AT）。通过肌腱内注射（0.8g/kg/mL）于第 3 和 6 天给予丝胶注射，DS 通过口服灌胃（1.1mg/kg/天）给药 14 天。测量血清总氧化应激状态（TOS-TAS）、TGF-β1、核心蛋白聚糖（decorin）、Smad2 和结缔组织生长因子（CTGF）的浓度。对跟腱样本进行组织病理学和免疫组织化学（IHC）研究。
与 C 和 ATN 相比，AT 中的 TOS、氧化应激指数（OSI）、TGF-β1、Smad2、CTGF 和 decorin 血清浓度显著升高，而 ATS 中的 TGF-β1、Smad2、CTGF 和 decorin 血清浓度显著降低（P<0.05）。组织病理学检查显示，AT 中不规则纤维、变性和圆形细胞核明显升高。与 C 相似的是，ATS 中的纺锤形纤维，变性减少。与 C 相比，AT 中 TGF-β1 和 Smad2/3 表达增加，胶原 I 型 alpha-1（Col1A1）表达减少（P=0.001）。在 ATS 中，TGF-β1 和 Smad2/3 表达减少，Col1A1 表达增加。Bonar 评分在 AT 组显著增加（P=0.001），在 ATS 组显著降低（P=0.027）。
丝胶在实验性 AT 大鼠模型中具有减轻氧化应激和调节 TGF-β/Smad 途径的潜力。它可能是治疗 AT 的一种有前途的治疗剂，需要进一步的临床研究来验证。关键点：• 本研究表明丝胶通过 TGF-β/Smad 途径减轻 AT 诱导的损伤。• ELISA 和 IHC 研究通过关键的 TGF-β/Smad 途径证实了丝胶在组织修复中的有效性。• 证据表明，丝胶增强了胶原合成，塑造了肌腱纤维结构，减少了组织病理学变性。• 丝胶的抗氧化特性在其 AT 治疗应用中得到了再次证实。
