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慢性振荡性葡萄糖刺激会打乱先天性免疫稳态,从而增强有或无隐匿性糖尿病大鼠中性粒细胞与淋巴细胞比值的变化。

Chronic oscillating glucose challenges disarrange innate immune homeostasis to potentiate the variation of neutrophil-lymphocyte ratio in rats with or without hidden diabetes mellitus.

作者信息

Yang Gaoxiong, Yan Rui, Tong Huanjun, Zhang Jitai, Chen Bin, Xue Xiangyang, Wang Jue, Chu Maoping, Jin Shengwei, Li Ming

机构信息

Cardiac Regeneration Research Institute, Wenzhou Medical University, Wenzhou, China.

School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, China.

出版信息

Diabetes Metab Syndr Obes. 2018 Jun 13;11:277-288. doi: 10.2147/DMSO.S160301. eCollection 2018.

DOI:10.2147/DMSO.S160301
PMID:29942142
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6005307/
Abstract

BACKGROUND

The neutrophil-lymphocyte ratio (NLR) has been considered as an inflammatory marker in various disorders, but it is not clear whether the NLR is also elevated with hidden diabetes (HD), which is normal in fasting blood glucose (FBG) but abnormal in the oral glucose tolerance test (OGTT).

MATERIALS AND METHODS

An HD animal model for 27 days and an animal model with oscillating glucose (OG) for 7 days were applied on adult female Sprague-Dawley rats. OGTT, leukogram analysis, histology, and immunohistochemistry were carried out.

RESULTS

In HD rats, the percentage of neutrophils increased but the percentage of lymphocytes decreased; hence, the NLR rose relative to sham. This may be a result of the OG levels often experienced by diabetic subjects, as normal rats given OG (6 g/kg/6 h) for 7 days had significantly reduced lymphocyte numbers and increased NLR compared with the values before and 1 h after oral glucose administration during OGTT. Glucose-induced disarrangement of partitions of circulating immune cells and NLR was involved in the increase in oxidative stress, as these changes were totally blocked by the antioxidant glutathione (GSH). GSH (50 mg/kg/6 h) totally blocked the glucose-induced alterations in lymphocyte and NLR values.

CONCLUSION

HD associated with elevation of NLR values may be partly attributed to a homeostasis disorder of the innate inflammatory state, caused by oscillating hyperglycemia. Acute high glucose administration produced a significant decrease in lymphocyte number. OG administration potentiated this effect and increased the NLR value, which was blocked by GSH, suggesting that reactive oxygen species play a critical role in maintaining lymphocyte numbers.

摘要

背景

中性粒细胞与淋巴细胞比值(NLR)在多种疾病中被视为一种炎症标志物,但目前尚不清楚在隐匿性糖尿病(HD)中NLR是否也会升高,HD患者空腹血糖(FBG)正常,但口服葡萄糖耐量试验(OGTT)异常。

材料与方法

对成年雌性Sprague-Dawley大鼠建立为期27天的HD动物模型和为期7天的血糖波动(OG)动物模型。进行了OGTT、血常规分析、组织学检查和免疫组化。

结果

在HD大鼠中,中性粒细胞百分比增加而淋巴细胞百分比降低;因此,与假手术组相比,NLR升高。这可能是糖尿病患者经常经历的血糖水平的结果,因为给予正常大鼠7天的OG(6 g/kg/6 h)后,与OGTT期间口服葡萄糖前和口服后1小时的值相比,淋巴细胞数量显著减少,NLR增加。葡萄糖诱导的循环免疫细胞分区紊乱和NLR与氧化应激增加有关,因为这些变化被抗氧化剂谷胱甘肽(GSH)完全阻断。GSH(50 mg/kg/6 h)完全阻断了葡萄糖诱导的淋巴细胞和NLR值的变化。

结论

与NLR值升高相关的HD可能部分归因于血糖波动引起的先天性炎症状态的稳态失调。急性高糖给药导致淋巴细胞数量显著减少。给予OG增强了这种作用并增加了NLR值,这被GSH阻断,表明活性氧在维持淋巴细胞数量中起关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f73/6005307/b70f969b26c9/dmso-11-277Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f73/6005307/eb050d0a8351/dmso-11-277Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f73/6005307/e2634ab31e0d/dmso-11-277Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f73/6005307/1742555c402b/dmso-11-277Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f73/6005307/f80ebd984f6e/dmso-11-277Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f73/6005307/b70f969b26c9/dmso-11-277Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f73/6005307/eb050d0a8351/dmso-11-277Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f73/6005307/e2634ab31e0d/dmso-11-277Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f73/6005307/1742555c402b/dmso-11-277Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f73/6005307/f80ebd984f6e/dmso-11-277Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f73/6005307/b70f969b26c9/dmso-11-277Fig5.jpg

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