Role of autophagic response in glutamine treatment attenuating inflammation in rats after traumatic brain injury

Q4 Nursing

中华临床营养杂志 Pub Date : 2018-04-30 DOI:10.3760/CMA.J.ISSN.1674-635X.2018.02.007

Xiaozhen Cai, Jian-hua Huang, Hai-Huan Zeng, Xuejuan Wang

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Abstract

Objective To investigate the effect of glutamine (GLN) treatment on neurobehavioral outcome, brain edema and inflammatory response in rats after traumatic brain injury (TBI), and to find out the role played by autophagic response in this effect. Methods Rat models with TBI in this study were established using Feeney's method. One hundred healthy male SD rats were randomly divided into five groups (n=20) to receive sham operation (group Sham), TBI (group TBI), TBI and glutamine treatment (group TBI+ GLN), TBI amd autophagy inhibitor 3-methyladenine (group TBI+ 3-MA), and TBI, GLN and autophagy inhibitor (group TBI+ GLN+ 3-MA). We measured the rats' behavioral outcomes by modified neurologic severity score (mNSS) tests at day 1, 3, 7 and 14 after intervention. Brain water content was measured with wet-dry weight method. The serum levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1 and IL-4 were tested using enzyme linked immunosorbent assay. The expressions of autophagy-related factors (LC3-Ⅱ, Beclin-1) in TBI cerebral cortex were tested with Western blot. Results Compared with the Sham group, the other four groups had significantly increased levels of brain edema, mNSS, serum inflammatory factors and cerebral LC3-Ⅱ and Beclin-1 (P=0.00). Compared with the TBI group, the TBI+ GLN group had less severe brain edema and improved mNSS, lower levels of TNF-α [(57.71±9.69)pg/ml vs. (83.37±12.81)pg/ml, P=0.01] and IL-1 [(39.46±8.60)pg/ml vs. (69.04±10.48)pg/ml, P=0.00], higher levels of IL-4 [(68.72±11.18)pg/ml vs. (35.75±8.40)pg/ml, P=0.04], and upregulated expressions of LC3-Ⅱ and Beclin-1 (P=0.01). Compared with the TBI+ GLN group, the TBI+ GLN+ 3-MA group had severer neurofunctional impairment, brain edema and inflammation (P<0.05). Conclusions Treatment with GLN markedly reduced brain edema and improved neurobehavioral outcomes in rats with TBI by inhibiting inflammatory response in the central nervous system. The mechanism might have been the activation of the autophagic response. Key words: Traumatic brain injury; Glutamine; Inflammation; Autophagy; Neuroprotection

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自噬反应在谷氨酰胺治疗减轻创伤性脑损伤大鼠炎症中的作用

目的探讨谷氨酰胺(GLN)对创伤性脑损伤(TBI)大鼠神经行为结局、脑水肿及炎症反应的影响，并探讨自噬反应在其中所起的作用。方法采用Feeney法建立大鼠脑外伤模型。选取健康雄性SD大鼠100只，随机分为5组(n=20)，分别接受假手术组(sham组)、TBI组(TBI组)、TBI+谷氨酰胺组(TBI+ GLN组)、TBI+自噬抑制剂3-甲基腺嘌呤组(TBI+ 3-MA组)、TBI+ GLN+自噬抑制剂3-甲基腺嘌呤组(TBI+ 3-MA组)。我们在干预后第1、3、7和14天通过改良神经系统严重程度评分(mNSS)测试测量大鼠的行为结果。采用干湿重法测定脑含水量。采用酶联免疫吸附法检测血清肿瘤坏死因子-α (TNF-α)、白细胞介素(IL)-1、IL-4水平。Western blot检测脑损伤后大脑皮层自噬相关因子(LC3-Ⅱ、Beclin-1)的表达。结果与Sham组比较，其他4组大鼠脑水肿、mNSS、血清炎性因子、脑LC3-Ⅱ、Beclin-1水平均显著升高(P=0.00)。与TBI组相比，TBI+ GLN组脑水肿程度较轻，mNSS改善，TNF-α水平[(57.71±9.69)pg/ml比(83.37±12.81)pg/ml, P=0.01]和IL-1水平[(39.46±8.60)pg/ml比(69.04±10.48)pg/ml, P=0.00]降低，IL-4水平[(68.72±11.18)pg/ml比(35.75±8.40)pg/ml, P=0.04]升高，LC3-Ⅱ和Beclin-1表达上调(P=0.01)。与TBI+ GLN组比较，TBI+ GLN+ 3-MA组神经功能损害、脑水肿、炎症加重(P<0.05)。结论GLN通过抑制中枢神经系统炎症反应，显著减轻脑损伤大鼠脑水肿，改善神经行为。其机制可能是自噬反应的激活。关键词:外伤性脑损伤;谷氨酰胺;炎症;自噬;神经保护

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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.