PDF(Pubmed)
Abstract：
BACKGROUND: One of the most common, but least studied, diabetic complication is diabetic bladder dysfunction. Current therapies include glucose control and symptom-based interventions. However, efficacy of these therapies is mixed and often have undesirable side effects. Diabetes is now known to be a chronic inflammatory disease. Specialized pro-resolving mediators are a class of compounds that promote the resolution of inflammation and have been shown to be effective in treating chronic inflammatory conditions. In this study we examine the ability of resolvin E1 to improve signs of diabetic bladder dysfunction.
METHODS: Male Akita mice (Type 1 diabetic) develop hyperglycemia at 4 weeks and signs of bladder underactivity by 15 weeks. Starting at 15 weeks, mice were given one or two weeks of daily resolvin E1 and compared to age-matched wild type and untreated Akita mice.
RESULTS: Resolvin E1 did not affect diabetic blood glucose after one week, although there was a slight decrease after two weeks. Diabetes decreased body weight and increased bladder weights and this was not affected by resolvin E1. Evan\'s blue dye extravasation (an indirect index of inflammation) was dramatically suppressed after one week of resolvin E1 treatment, but, surprisingly, had returned to diabetic levels after two weeks of treatment. Using cystometry, untreated Akita mice showed signs of underactivity (increased void volumes and intercontraction intervals). One week of resolvin E1treatment restored these cystometric findings back to control levels. After two weeks of treatment, cystometric changes were changed from controls but still significantly different from untreated levels, indicating a durable treatment effect even in the presence of increased inflammation at 2 weeks.
CONCLUSIONS: Resolvin E1 has a beneficial effect on diabetic bladder dysfunction in the type 1 diabetic male Akita mouse model.
METHODS: Male Akita mice (Type 1 diabetic) develop hyperglycemia at 4 weeks and signs of bladder underactivity by 15 weeks. Starting at 15 weeks, mice were given one or two weeks of daily resolvin E1 and compared to age-matched wild type and untreated Akita mice.
RESULTS: Resolvin E1 did not affect diabetic blood glucose after one week, although there was a slight decrease after two weeks. Diabetes decreased body weight and increased bladder weights and this was not affected by resolvin E1. Evan\'s blue dye extravasation (an indirect index of inflammation) was dramatically suppressed after one week of resolvin E1 treatment, but, surprisingly, had returned to diabetic levels after two weeks of treatment. Using cystometry, untreated Akita mice showed signs of underactivity (increased void volumes and intercontraction intervals). One week of resolvin E1treatment restored these cystometric findings back to control levels. After two weeks of treatment, cystometric changes were changed from controls but still significantly different from untreated levels, indicating a durable treatment effect even in the presence of increased inflammation at 2 weeks.
CONCLUSIONS: Resolvin E1 has a beneficial effect on diabetic bladder dysfunction in the type 1 diabetic male Akita mouse model.
摘要：
背景：最常见的，但研究最少,糖尿病并发症是糖尿病膀胱功能障碍。目前的治疗包括血糖控制和基于症状的干预。然而,这些疗法的功效是混合的并且通常具有不良副作用。现在已知糖尿病是一种慢性炎性疾病。专门的促炎介质是一类促进炎症消退的化合物,并且已经显示出在治疗慢性炎性病症中是有效的。在这项研究中，我们检查了消退素E1改善糖尿病膀胱功能障碍体征的能力。
方法:雄性秋田小鼠(1型糖尿病小鼠)在4周时出现高血糖症,并在15周时出现膀胱活动不足的迹象。从15周开始，每天给予小鼠一到两周的消退素E1，并与年龄匹配的野生型和未经治疗的Akita小鼠进行比较。
结果：ResolvinE1在一周后对糖尿病血糖没有影响，尽管两周后略有下降。糖尿病降低了体重，增加了膀胱重量，而这不受消退素E1的影响。Evan的蓝色染料外渗（炎症的间接指数）在消退E1治疗一周后被显著抑制，但是,令人惊讶的是,治疗两周后恢复到糖尿病水平。用膀胱测压法,未经处理的秋田小鼠表现出活动不足的迹象(空隙体积和收缩间隔增加)。一周的消退蛋白E1治疗使这些膀胱测量结果恢复到对照水平。经过两周的治疗,膀胱测量变化与对照组相比有所改变，但与未治疗水平仍有显著差异，表明即使在2周时炎症增加的情况下也具有持久的治疗效果。
结论：ResolvinE1在1型糖尿病雄性秋田小鼠模型中对糖尿病膀胱功能障碍具有有益作用。
方法:雄性秋田小鼠(1型糖尿病小鼠)在4周时出现高血糖症,并在15周时出现膀胱活动不足的迹象。从15周开始，每天给予小鼠一到两周的消退素E1，并与年龄匹配的野生型和未经治疗的Akita小鼠进行比较。
结果：ResolvinE1在一周后对糖尿病血糖没有影响，尽管两周后略有下降。糖尿病降低了体重，增加了膀胱重量，而这不受消退素E1的影响。Evan的蓝色染料外渗（炎症的间接指数）在消退E1治疗一周后被显著抑制，但是,令人惊讶的是,治疗两周后恢复到糖尿病水平。用膀胱测压法,未经处理的秋田小鼠表现出活动不足的迹象(空隙体积和收缩间隔增加)。一周的消退蛋白E1治疗使这些膀胱测量结果恢复到对照水平。经过两周的治疗,膀胱测量变化与对照组相比有所改变，但与未治疗水平仍有显著差异，表明即使在2周时炎症增加的情况下也具有持久的治疗效果。
结论：ResolvinE1在1型糖尿病雄性秋田小鼠模型中对糖尿病膀胱功能障碍具有有益作用。
