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目的探讨三氮脒(diminazene aceturate,DIZE)是否能减轻内毒素诱导性小鼠葡萄膜炎。方法连续给予一般情况良好、体质量16～20 g的雌性BALB/c小鼠腹腔内注射DIZE(60 mg/kg)2 d后,将125 ng脂多糖(lipopolysaccharides,LPS)注射入小鼠玻璃体内建立内毒素诱导性葡萄膜炎模型。分别于注射LPS后12、24 h观察小鼠眼前房炎症情况并进行临床评分。第24小时摘除眼球,石蜡切片HE染色观察小鼠眼部形态学变化。用Real-time PCR检测小鼠眼内炎症细胞因子表达。结果在注射LPS 12 h后DIZE对眼前房炎症出现明显的保护作用。24 h时DIZE+LPS组的临床评分[(1.75±0.96)分]明显低于生理盐水+LPS组[(4.00±1.22)分](P<0.01);HE染色结果显示DIZE+LPS组小鼠玻璃体内渗出的炎症细胞数明显少于生理盐水+LPS组,但各组小鼠视网膜结构和层次无明显改变。DIZE+LPS组的小鼠眼内细胞间黏附分子-1(intercellular adhesion molecule-1,ICAM-1)、TNF-α、单核细胞趋化蛋白(monocyte chemoattractant protein-1,MCP-1)、IL-6的mRNA水平明显低于生理盐水+LPS组(P<0.01)。结论 DIZE在LPS引起的内毒素诱导性小鼠葡萄膜炎的眼部炎症中起保护作用,有望成为一种治疗葡萄膜炎的新药。
Objective To investigate whether diminzene aceturate (DIZE) can attenuate endotoxin-induced mouse uveitis. Methods After continuous intraperitoneal injection of DIZE (60 mg / kg) into BALB / c mice with a body weight of 16-20 g for 2 days, 125 ng lipopolysaccharides (LPS) were injected intravitreally Endotoxin-induced uveitis model was established. The anterior chamber inflammation in mice was observed 12 and 24 h after LPS injection, respectively, and clinical scores were observed. At the 24th hour, the eyes were removed, and the morphological changes in the eyes of the mice were observed by HE staining. Real-time PCR was used to detect intraocular inflammatory cytokine expression in mice. Results DIZE showed obvious protective effect on anterior chamber inflammation after 12 h injection of LPS. The clinical score of DIZE + LPS group was significantly lower than that of saline + LPS group (4.00 ± 1.22) (P <0.01) at 24 h (P <0.01) The number of inflammatory cells exuding in the vitreous body was significantly less than that in the saline + LPS group, but there was no significant change in the retinal structure and level in each group. Intercellular adhesion molecule-1 (ICAM-1), TNF-α, monocyte chemoattractant protein-1 (MCP-1), interleukin- -6 mRNA level was significantly lower than saline + LPS group (P <0.01). Conclusion DIZE plays a protective role in LPS-induced ocular inflammation of endotoxin-induced mouse uveitis and is expected to become a new drug for the treatment of uveitis.