Establishment of animal model of Blau syndrome / 中国药理学通报

ABSTRACT

Aim To establish stable and reliable animal models of Blau syndrome (BS) in vivo. Methods C57BL/6J mice were intraperitoneally injected with muramyl dipeptide (MDP) or L18-MDP to induce systemic inflammatory model of BS. Meanwhile, positive drug etanercept (ETN) was set to investigate the response of the model to evaluate effectiveness. SD rats were intravitrealiy injected with MDP to establish BS-associated uveitis model. Serum levels of TNF-a, IL-6 and IL-8 were detected by enzyme linked immunosorbent assay (ELISA). Histopathologic al changes of rat eyeballs were detected by HE staining and the expressions of p65, p-ERK, p-p38, p-JNK, TNF-a, IL-6 and IL-8 in vitreous were determined by immunohistochem-istry (IHC) staining. Results The serum level of TNF-a in mice increased after intraperitoneal injection of MDP (P < 0.05), and increased significantly after L18-MDP injection (P < 0.01). Meanwhile, the levels of IL-6 and IL-8 were also markedly induced by L18-MDP (P < 0. 01, P < 0. 01). ETN treatment evidently inhibited the increased levels of these above cytokines induced by L18-MDP (P < 0. 05, P < 0. 01). After the intravitreous injection of MDP in SD rats, there were numerous inflammatory cells infiltrated in retina and vitreous, and the retina was seriously damaged. The staining levels of p65, p-ERK, p-p38, p-JNK, TNF-a, IL-6 and IL-8 in eyeball tissues were significantly enhanced. Conclusions The systemic animal model of BS can be successfully established by intraperitoneal injection of L18-MDP in C57BL/6J mice, and the good BS-relat-ed uveitis can be induced by intravitreous injection of MDP in SD rats, which provides the simple, convenient, repeatable and i-deal animal models for exploring the pathogenesis of BS and e-valuating the efficacy of drugs.