PPARγ配体盐酸吡格列酮对MRL/lpr小鼠泪腺炎症干预的研究

Effect of hydrochloride pioglitazone on inflammation of lacrimal gland in MRL/lpr mice

目的研究过氧化物酶增殖体激活受体γ(peroxisome proliferator activated receptorγ,PPARγ)激动剂盐酸吡格列酮对干眼模型MRL/lpr小鼠泪腺的影响。方法 12周龄MRL/lpr及BLAB/C雌性小鼠各30只,随机分为空白对照组、空白干预组、干眼对照组、干眼干预组。对空白干预组及干眼干预组行盐酸吡格列酮溶液灌胃干预(60 mg/kg)。8周后酚红棉线实验检测泪液分泌情况;取各组小鼠泪腺组织行H-E染色,分析淋巴细胞浸润情况;免疫组织化学法及Western印迹法检测泪腺组织炎症因子TNF-α、PPARγ的IL-1β表达情况。结果干眼干预组小鼠泪液分泌量显著大于其他各组(P<0.05),淋巴细胞浸润情况明显少于干眼对照组,泪腺炎症因子TNF-α和IL-1β表达明显低于干眼对照组,PPARγ表达显著高于干眼对照组(P<0.05)。结论对MRL/lpr干眼模型小鼠进行盐酸吡格列酮溶液灌胃干预后,可激活PPARγ并使其上调,抑制炎症因子TNF-α及IL-1β的表达,从而干预干眼炎症的进程,改善干眼动物体征及泪腺损害。

Objective To investigate the effect of proxisome proliferators-activated receptor -γ （PPARγ） ligand hydrochloride pioglitazone on the lacrimal gland of MRL/lpr mice. Methods Female MRL/lpr mice （dry eye model） and BLAB/C mice （control） of 12 weeks were randomly divided into 4 groups： dry eye group, dry eye ＋ pioglitazone treatment group, control group and control ＋ pioglitazone group. Mice in groups dry eye ＋ pioglitazone treatment group and control ＋ pioglitazone group were treated with hydrochloride pioglitazone 60 mg/kg daily by oral gavage. Cotton thread test performed 8 weeks after treatment. H-E analyze the invasion of lymphocytes. Expressions interleukin-1β （IL-1β） in lacrimal gland were staining was carried out for lacrimal gland tissues to of PPARγ, tumor necrosis factor-a （TNF-a） and examined by immunohistochemistry staining and Western blotting. Results Tear production was mcreasect mtary eye ＋ pioglitzaone treatment group than that in other groups （ P 〈 0.05 ）. H-E staining showed less invaded lymphocytes in dry eye ＋ pioglitazone treatment group compared with dry eye group. Immunohistochemistry staining showed that the expression of inflammatory factors TNF-a and 1L-1 β was decreased in dry eye ＋ pioglitazone treatment group. Western blotting revealed that the expression of PPARγ protein was increased and TNF-a and IL-1 β was decreased in dry eye ＋ pioglitazone treatment group compared to dry eye group. Conclusion Hydrochloride pioglitazone can intervene the progress of dry eye, which may be associated with up-regulating PPARγ expression and down-regulation TNF-a and IL-1 β expression.