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丝素蛋白丝胶:一种有前途的跟腱病治疗方法——来自实验大鼠模型的证据。

Silk protein sericin: a promising therapy for Achilles tendinopathy-evidence from an experimental rat model.

机构信息

Department of Physiology, Faculty of Medicine, Pamukkale University, Denizli, Turkey.

Department of Orthopedics and Traumatology, Denizli State Hospital, Denizli, Turkey.

出版信息

Clin Rheumatol. 2023 Dec;42(12):3361-3373. doi: 10.1007/s10067-023-06767-6. Epub 2023 Sep 21.

Abstract

OBJECTIVE

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).

METHOD

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.

RESULTS

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).

CONCLUSION

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.

摘要

目的

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。

方法

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。

结果

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)。

结论

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。

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