Yoo Ki Yeon, Lee Hee Su, Cho Young Kyung, Lim You Sun, Kim Yi Seul, Koo Jung Hoi, Yoon Se Jin, Lee Jung Hwan, Jang Ki Hyo, Song Sun Hong
Department of Oral Anatomy, Gangneung-Wonju National University, Gangneung, Republic of Korea.
Neurotox Res. 2014 Jul;26(1):32-9. doi: 10.1007/s12640-013-9447-7. Epub 2013 Dec 12.
The objective of the study is to verify histopathologically the anti-inflammatory effect of botulinum toxin type A (BoNT-A) in a Complete Freund's Adjuvant (CFA)-induced arthritic knee joint of hind leg on rat model using immunofluorescent staining of anti-ionized calcium-binding adaptor molecule 1 (Iba-1) and interleukin-1β (IL-1β) antibody. Twenty-eight experimental rats were injected with 0.1 ml of CFA solution in the knee joint of the hind leg bilaterally. Three weeks after CFA injection, the BoNT-A group (N = 14) was injected with 20 IU (0.1 ml) of BoNT-A bilaterally while the saline group (N = 14) was injected with 0.1 ml of saline in the knee joint of the hind leg bilaterally. One and two weeks after BoNT-A or saline injection, joint inflammation was investigated in seven rats from each group using histopathological and immune-fluorescent staining of Iba-1 and IL-1β antibody. The number of Iba-1 and IL-1β immune-reactive (IR) cells was counted in the BoNT-A and saline groups for comparison. There was a significant reduction in joint inflammation and destruction in the BoNT-A group at 1 and 2 weeks after BoNT-A injection compared with the saline group. The binding of Iba-1 and IL-1β antibody was significantly lower in the BoNT-A group than the saline group at 1 and 2 weeks after BoNT-A injection. The number of Iba-1 and IL-1β-IR cells at 1 and 2 weeks after the injection of BoNT-A were significantly different from the corresponding number of Iba-1 and IL-1β-IR cells in the saline group. To conclude, BoNT-A had an anti-inflammatory effect in a CFA-induced arthritic rat model, indicating that BoNT-A could potentially be used to treat inflammatory joint pain.
本研究的目的是通过对抗离子钙结合衔接分子1(Iba-1)和白细胞介素-1β(IL-1β)抗体进行免疫荧光染色,从组织病理学角度验证A型肉毒杆菌毒素(BoNT-A)对完全弗氏佐剂(CFA)诱导的大鼠后肢膝关节关节炎的抗炎作用。28只实验大鼠双侧后肢膝关节注射0.1 ml CFA溶液。CFA注射三周后,BoNT-A组(N = 14)双侧膝关节注射20 IU(0.1 ml)BoNT-A,而生理盐水组(N = 14)双侧后肢膝关节注射0.1 ml生理盐水。在BoNT-A或生理盐水注射后1周和2周,使用Iba-1和IL-1β抗体的组织病理学和免疫荧光染色对每组7只大鼠的关节炎症进行研究。对BoNT-A组和生理盐水组中Iba-1和IL-1β免疫反应(IR)细胞的数量进行计数以作比较。与生理盐水组相比,BoNT-A组在注射BoNT-A后1周和2周时关节炎症和破坏明显减轻。在注射BoNT-A后1周和2周,BoNT-A组中Iba-1和IL-1β抗体的结合明显低于生理盐水组。注射BoNT-A后1周和2周时Iba-1和IL-1β-IR细胞的数量与生理盐水组中相应的Iba-1和IL-1β-IR细胞数量有显著差异。总之,BoNT-A在CFA诱导的关节炎大鼠模型中具有抗炎作用,表明BoNT-A可能有潜力用于治疗炎性关节疼痛。