补充谷氨酰胺通过抑制创伤性脑损伤后小胶质细胞介导的神经炎症反应提供神经保护

Q4 Nursing

中华临床营养杂志 Pub Date : 2018-12-30 DOI:10.3760/CMA.J.ISSN.1674-635X.2018.06.009

Dandan Huang, Shasha Xie, Fan Pan

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The microglia polarization relatived protein (Iba-1, CD16, CD86) expressions in TBI cerebral cortices were determined by immunohistochemistry staining and western blotting, respectively. While, the serum levels of tumor necrosis factor-α(TNF-α), interleukin (IL)-1 and interferon (IFN)-γ were tested by enzyme linked immunosorbent Assay (ELISA). \n \n \nResults \nCompared with the Con group, the levels of neurobehavioral outcome, neurons apoptosis, microglia polarization and neuroinflammatory factors were significantly increased in the other two groups(P=0.00). Compared with the TBl group, glutamin supplementation improved neurobehavioral outcome[7 d: (10.74±0.25)points vs. (8.94±0.24) points, P=0.01; 14 d: (8.77±0.16)points vs. (7.43±0.13)points, P=0.03]. 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引用次数: 0

摘要

目的探讨补充谷氨酰胺（Gln）对大鼠创伤性脑损伤（TBI）后神经行为结果、神经元凋亡、小胶质细胞极化和神经炎症反应的影响及其机制。方法采用Feeney法建立TBI动物模型。60只Wistar大鼠随机分为三组：对照组（Con）、颅脑损伤组（TBI）和谷氨酰胺补充组（TBI+Gln）。我们在TBI后第1、3、7和14天通过改良神经严重程度评分（mNSS）测试来测量大鼠的行为结果。Nissl染色法检测凋亡神经元。用免疫组织化学染色和免疫印迹法分别测定小胶质细胞极化相关蛋白（Iba-1，CD16，CD86）在脑外伤性脑皮质中的表达。采用酶联免疫吸附试验（ELISA）检测血清肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-1和干扰素（IFN）-γ水平。结果与Con组相比，其他两组的神经行为结果、神经元凋亡、小胶质细胞极化和神经炎症因子水平均显著升高（P=0.00），谷氨酰胺补充改善了神经行为结果[7d:（10.74±0.25）分对（8.94±0.24）分，P=0.01]；14d:（8.77±0.16）分对“7.43±0.13”分，P=0.03]，抑制Iba-1和CD16的蛋白表达，并增加CD86的蛋白质表达，促进小胶质细胞从M1表型向M2表型的转变，抑制小胶质细胞的活化，从而降低TBI诱导的神经炎症因子[TNF-α：（125.42±12.81）pg/ml vs.（74.36±9.25）pg/ml，P=0.01；IL-1:（69.04±8.48）pg/ml vs（34.73±3.92）pg/ml；P=0.01；TNF-α：，可能是通过促进小胶质细胞从M1表型向M2表型的表型转变从而减少TBI诱导的神经炎症因子介导的。关键词：创伤性脑损伤；谷氨酰胺；小胶质细胞；炎症反应；神经保护

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Glutamine supplementation provides neuroprotection by inhibiting microglia-mediated neuroinflammatory response after traumatic brain injury in rats

Objective To investigate the effects and mechanisms of Glutamine(Gln) supplementation on neurobehavioral outcome, neuronal apoptosis, microglia polarization, and neuroinflammatory response after traumatic brain injury (TBI) in rats. Methods TBI animal models were established using Feeney's method. Sixty Wistar rats were randomly divided into three groups: control group (Con), traumatic brain injury group (TBI), and glutamine supplementation group (TBI+ Gln). We measured rat behavioral outcomes by modified neurologic severity score (mNSS) tests at day 1, 3, 7 and 14 after TBI. Apoptotic neurons were determined by Nissl staining. The microglia polarization relatived protein (Iba-1, CD16, CD86) expressions in TBI cerebral cortices were determined by immunohistochemistry staining and western blotting, respectively. While, the serum levels of tumor necrosis factor-α(TNF-α), interleukin (IL)-1 and interferon (IFN)-γ were tested by enzyme linked immunosorbent Assay (ELISA). Results Compared with the Con group, the levels of neurobehavioral outcome, neurons apoptosis, microglia polarization and neuroinflammatory factors were significantly increased in the other two groups(P=0.00). Compared with the TBl group, glutamin supplementation improved neurobehavioral outcome[7 d: (10.74±0.25)points vs. (8.94±0.24) points, P=0.01; 14 d: (8.77±0.16)points vs. (7.43±0.13)points, P=0.03]. Meanwhile, glutamin supplementation suppressed the apoptotic rates of neurons [3 d: (80.18±8.38)% vs.(65.47±7.02)%, P=0.01; 7 d: (58.90±6.12)% vs.(42.73±4.88)%, P=0.01; 14 d: (39.56±2.95)% vs.(31.12±3.16)%, P=0.01], inhibited protein expressions of Iba-1 and CD16, and increased the protein expression of CD86, which promoted the phenotypic shift of microglia from M1 to M2 phenotype, inhibited microglial activation, and thus reduced TBI-induced neuroinflammatory factors [TNF-α: (125.42±12.81)pg/ml vs. (74.36±9.25)pg/ml, P=0.01; IL-1: (69.04±8.48)pg/ml vs. (34.73±3.92)pg/ml, P=0.01; TNF-α: (89.75±9.40)pg/ml vs. (45.62±6.64)pg/ml, P=0.02]. Conclusion Glutamine supplementation can markedly reduce neuron apoptosis and improve neurological outcomes after TBI, possibly mediated by promoting the phenotypic shift of microglia from M1 to M2 phenotype and thus reducing TBI-induced neuroinflammatory factors. Key words: Traumatic brain injury; Glutamine; Microglia; Inflammatory response; Neuroprotection

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来源期刊

中华临床营养杂志 Nursing-Nutrition and Dietetics

CiteScore

0.20

自引率

0.00%

发文量

2282

期刊介绍： The Chinese Journal of Clinical Nutrition was founded in 1993. It is the first professional academic journal (bimonthly) in my country co-sponsored by the Chinese Medical Association and the Chinese Academy of Medical Sciences to disseminate information on clinical nutrition support, nutrient metabolism, the impact of nutrition support on outcomes and "cost-effectiveness", as well as translational medicine and nutrition research. It is also a professional journal of the Chinese Medical Association's Parenteral and Enteral Nutrition Branch. The purpose of the Chinese Journal of Clinical Nutrition is to promote the rapid dissemination of knowledge on nutrient metabolism and the rational application of parenteral and enteral nutrition, focusing on the combination of multidisciplinary and multi-regional field investigations and clinical research. It mainly reports on nutritional risk screening related to the indications of parenteral and enteral nutrition support, "cost-effectiveness" research on nutritional drugs, consensus on clinical nutrition, guidelines, expert reviews, randomized controlled studies, cohort studies, glycoprotein and other nutrient metabolism research, systematic evaluation of clinical research, evidence-based case reports, special reviews, case reports and clinical experience exchanges, etc., and has a special column on new technologies related to the field of clinical nutrition and their clinical applications.