An experimental study for temporomandibular joint arthritis using with ultrasound gene induction

白细胞介素-1 （IL-1）在包括颞下颌关节在内的许多关节的关节炎发病机制中起主导作用。外源性IL-1受体拮抗剂（IL-1ra）可有效降低IL-1介导的炎症反应。由于细胞因子本身的施用非常昂贵且仅在短时间内起作用，因此认为这种拮抗剂的基因诱导是值得的。最近，非病毒基因诱导被认为比病毒基因诱导更安全，这项研究的目的是评估IL-1ra基因诱导在佐剂性关节炎中的疗效。将19只Lewis大鼠分为对照组、人IL-1ra基因诱导关节炎组和空质粒诱导关节炎组。采用常规方法诱导关节炎。体内超声探查4次；注射佐剂前14天和7天，注射佐剂后第1天和7天。临床评价基因诱导的效果，并发关节炎后肢肿胀。在佐剂注射后第17天用已公布的评分系统进行组织病理学评估。与空质粒组相比，IL-1ra诱导组关节炎发病延迟。注射佐剂后第17天，IL-1ra诱导组和空质粒组大鼠后爪体积分别增加0.26 0.03 ml和0.76 0.09 ml。超声诱导IL-1ra后足肿胀明显减轻。IL-1ra诱导组关节炎评分明显低于空质粒组。结论体内IL-1ra基因诱导对佐剂性关节炎有明显的减轻作用。

Interleukin-1 (IL-1) plays dominant roles in pathogenesis of arthritic conditions in many joints including the temporomandibular joint. Administration of exogenous IL-1 receptor antagonist (IL-1ra) is found to be effective in reducing inflammatory response mediated by IL-1. Snce administration of cytokine itself is very costly and works only for short period, gene induction of this kind of antagonists is thought to be worthy. Recently, nonviral gene induction, which is thought to be safer than viral gene induction, has been developed The aim of this study was to evaluate the efficacy of IL-1ra gene induction in adjuvant-induced arthritis. Nineteen Lewis rats were divided into three groups, i.e., control, arthritis with human IL-1ra gene induction and arthritis with empty plasmid induction. Arthritis was induced with conventional manner. In vivo sonoporation was performed 4 times ; 14 days and 7 days prior to injection of adjuvant, the day and 7 days after injection of adjuvant. The efficacy of the gene induction was evaluated clinically with hind paw swelling following development of arthritis. Histopathological evaluation was done on day 17 post-adjuvant injection with a published scoring system. The onset of arthritis in the IL-1ra induction group was delayed comparing with the empty plasmid group. On day 17 post-adjuvant injection, the volume of the hind paw increased 0.26 0.03 ml and 0.76 0.09 ml in the IL-1ra induction group and in the empty plasmid group, respectively. The swelling of hind paw was significantly reduced by IL-1ra induction with sonoporation. The arthritic scores in the IL-1ra induction group were significantly lower than those of the empty plasmid group. As conclusions in vivo IL-1ra gene induction is effective far reduction of arthritis in adjuvant induced arthritis.