Beneficial effects of troglitazone on neutrophil dysfunction in multiple low-dose streptozotocin-induced diabetic mice
Beneficial effects of troglitazone on neutrophil dysfunction in multiple low-dose streptozotocin-induced diabetic mice
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DOI：
10.1111/j.1365-2249.2004.02532.x
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发表时间：
2004-08-01
影响因子：
4.6
通讯作者：
Nakamura, Y
中科院分区：
文献类型：
--
作者：
Kannan, Y;Tokunaga, M;Nakamura, Y
糖尿病控制不佳的患者感染细菌的风险很高。然而，关于糖尿病中性粒细胞功能的报道却相互矛盾。我们定期评估多次小剂量链脲佐菌素(STZ)诱导的糖尿病小鼠的中性粒细胞功能障碍，然后评估曲格列酮和其他噻唑烷二酮(TZDS)对中性粒细胞功能下降的影响。腹腔注射酵母多糖，检测中性粒细胞的浸润和吞噬功能。糖尿病小鼠腹腔中性粒细胞对酵母多糖的吞噬能力持续下降，中性粒细胞浸润在注射STZ后第30天减少，但在第40天有所增加。在糖尿病小鼠中，没有服用酵母多糖的小鼠血液中性粒细胞的体外趋化和吞噬活性持续降低。佛波酯(PMA)刺激酵母多糖诱导的中性粒细胞产生超氧化物歧化产物，降低酵母多糖诱导的肿瘤坏死因子-α和白介素1-β在糖尿病小鼠腹腔液中的水平。注射链脲佐菌素2周后开始使用曲格列酮治疗糖尿病小鼠，不能改善高血糖，但能阻止酵母多糖诱导的中性粒细胞在第30天的减少，并在第40天促进中性粒细胞的增加。曲格列酮还能促进体外分离的正常小鼠血中中性粒细胞的趋化活性。罗格列酮也有类似的作用，但吡格列酮不起作用。无论在体内还是体外，曲格列酮均不能增强中性粒细胞吞噬功能。综上所述，中性粒细胞功能受到STZ诱导的糖尿病的损害，但炎症浸润并不总是随着趋化障碍或细胞因子水平的变化而变化。此外，曲格列酮和罗格列酮至少可以改善这些动物的中性粒细胞趋化活性。
Patients with poorly controlled diabetes are at high risk of acquiring bacterial infections. However, conflicting results have been reported on neutrophil function in diabetes. We periodically evaluated neutrophil dysfunction in multiple low-dose streptozotocin (STZ)-induced diabetic mice, and then evaluated the effects of troglitazone and other thiazolidinediones (TZDs) on the decline of neutrophil function. Zymosan was injected intraperitoneally and neutrophil infiltration and phagocytosis were evaluated. While phagocytosis of zymosan by peritoneal neutrophils was consistently reduced in diabetic mice, neutrophil infiltration was decreased on day 30, but increased on day 40 after STZ injection. The in vitro chemotactic and phagocytic activities of blood neutrophils in mice that did not receive zymosan were consistently reduced in diabetic mice. Phorbol myristate acetate (PMA)-stimulated superoxide production by zymosan-induced peritoneal neutrophils and the levels of zymosan-induced tumour necrosis factor (TNF)-alpha and interleukin (IL)-1beta in peritoneal exudate fluids were also reduced in the diabetic mice. Treatment of the diabetic mice with troglitazone beginning 2 weeks after STZ injection did not improve hyperglycaemia but did prevent the decline of zymosan-induced neutrophil infiltration on day 30, and additionally promoted the increased infiltration on day 40. Troglitazone also promoted the chemotactic activity of blood neutrophils isolated from normal mice in vitro. Rosiglitazone but not pioglitazone induced a similar effect. Neutrophil phagocytosis was not enhanced by troglitazone either in vivo or in vitro. Taken together, neutrophil function is impaired by STZ-induced diabetes, but inflammatory infiltration does not always vary with the chemotactic disability or cytokine levels. Furthermore, troglitazone and rosiglitazone were suggested to improve at least neutrophil chemotactic activity in these animals.