米诺环素抑制内毒素诱导的大鼠眼内炎症反应

目的： 观察米诺环素对内毒素（LPS）诱导的大鼠眼内炎症的抑制作用。方法: SD大鼠玻璃体腔内1次注入LPS（1 μg）建立LPS诱导的眼内炎动物模型。在LPS注射前12 h和术中及术后连续3 d每天腹腔内注射米诺环素（45 mg/kg）。在LPS注入后6、12、24、48和72 h，裂隙灯显微镜下进行眼部炎症评分，组织病理学切片进行眼内浸润白细胞计数，并测定玻璃体内肿瘤坏死因子-α水平和前房水蛋白质浓度。结果: 在LPS注射后所有时点，米诺环素治疗均可明显减轻LPS诱导的眼内炎症，明显抑制玻璃体腔内白细胞浸润［LPS注射后24 h，眼内炎组（EO）为(1 182.63±191.15)细胞/每眼，眼内炎+米诺环素治疗组（EMT）为(291.50±63.77)细胞/每眼， P<0.01］并下调玻璃体腔内TNF-α的分泌水平［LPS注射后24 h，EO组为(931.17±99.81)ng/L，EMT组为(353.02±71.67)ng/L， P<0.01］。与EO组比较，EMT组各时点前房水蛋白质浓度改变无显著差异（P>0.05）。结论: 米诺环素通过抑制白细胞的眼内浸润和减少TNF-α的分泌，可明显抑制LPS诱导的眼内炎症反应。这些结果进一步证实白细胞眼内浸润和TNF-α分泌在LPS诱导的眼内炎发病机制中的作用，提示米诺环素在细菌性眼内炎的潜在治疗应用前景。

Minocycline inhibits rat ocular inflammation induced by lipopolysaccharide

AIM: To investigate the inhibitory effect of minocycline on the ocular inflammation induced by lipopolysaccharide in the rats. METHODS: Experimental endophthalmitis was induced in Sprague-Dawley rats by a single intravitreal injection of lipopolysaccharide (LPS of Escherichia coli, 1 μg). Minocycline (45 mg/kg) was administered intraperitoneally 12 h before and immediately after LPS injection and then every 24 h for 3 d. At 6, 12, 24, 48 and 72 h after LPS injection, eyes were graded daily for signs of clinical inflammation by slit lamp examination. The inflammatory cells were counted on histological sections. Vitreous was removed for cytokine analysis using standard enzyme-linked immunosorbent assay. Protein concentration in aqueous humor was determined.RESULTS: At all time points after LPS injection, significant clinical inhibition of ocular inflammation in the eye was observed in minocycline-treated rats. Quantitative analysis of ocular tissues revealed a significant decrease in infiltrated leukocytes ［(1 182.63±191.15) cells/eye in endophthalmitis group and (291.50±63.77) cells/eye in minocycline-treated group at 24 h postinjection, P<0.01］. Treatment with minocycline decreased tumor necrosis factor-α levels in vitreous ［(931.17±99.81)ng/L in endophthalmitis group and (353.02±71.67)ng/L in minocycline-treated group at 24 h postinjection, P<0.01］. Protein concentration in aqueous humor was decreased also, but the differences between the two groups at each time point was small and not significant (P>0.05).CONCLUSION: Minocycline treatment inhibits LPS-induced ocular inflammation with inhibition of tumor necrosis factor-α release and leukocytes infiltration. These results confirm the role of the tumor necrosis factor-α pathway and leukocytes infiltration in the pathogenesis of LPS-induced endophthalmitis, suggesting that minocycline may represent an attractive candidate for the therapeutic management of endophthalmitis.