{"title":"谷氨酰胺补充对大鼠颅脑损伤后氧化应激和自噬反应的抑制作用","authors":"Shukai Wu, Xiangrong Chen, Yasong Li, L. Luo","doi":"10.3760/CMA.J.ISSN.1674-635X.2019.02.004","DOIUrl":null,"url":null,"abstract":"Objective \nTo investigate the effects and mechanisms of glutamine(Gln) supplementation on oxidative stress, autophagy response and neurobehavioral outcome after traumatic brain injury (TBI) in rats. \n \n \nMethods \nTBI animal models were established using Feeney's method. Eighty SD rats were randomly divided into 4 groups: sham operation group (group Sham), Sham + glutamine supplementation group (group Sham+ GLN), traumatic brain injury group (group TBI), and TBI + glutamine supplementation group (group TBI+ GLN). We measured rat behavioral outcomes by modified neurologic severity score (mNSS) tests at day 1, 3, 7 and 14 after TBI. The apoptosis neurons in TBI cerebral cortex were determined by TUNEL staining. The expression of reactive oxygen species (ROS) was tested by ROS kits. Oxidative stress and autophagy related cytokines (HO-1, NQO1, Nrf2, LC3-Ⅱ and Beclin-1) were tested with Western blotting. \n \n \nResults \nCompared with the TBI group, the neurological function was improved[(9.79±0.43)vs.(8.43±0.30), F=6.775, P=0.010] and the apoptosis rate decreased(19.88% ±1.60% vs. 15.35% ±1.28%, P=0.013) in the TBI+ GLN group after 7-day treatment. Compared with the Sham group, the protein expression of ROS increased(P=0.000), and the expression of anti-oxidative stress factors (HO-1, NQO1) and Nrf2 pathway significantly decreased in the TBI group. After glutamine supplementation was given, the expression of ROS decreased and the expressions of HO-1 and NQO1 increased. The Nrf2 pathway and autophagy response also were activated with the expressions of Nrf2, LC3-Ⅱ and Beclin-1 increasing. \n \n \nConclusion \nGlutamine supplementation can markedly reduce neuron apoptosis and improve neurological outcomes after TBI, thus has the protective effect on nerves by inhibiting TBI-induced oxidative stress response, activating Nrf2 pathway and autophagy response. \n \n \nKey words: \nTraumatic brain injury; Glutamine; Oxidative stress; Nrf2 pathway; Autophagy","PeriodicalId":9877,"journal":{"name":"中华临床营养杂志","volume":"27 1","pages":"84-89"},"PeriodicalIF":0.0000,"publicationDate":"2019-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Neuroprotective effect of glutamine supplementation by inhibiting oxidative stress and promoting autophagy responses after traumatic brain injury in rats\",\"authors\":\"Shukai Wu, Xiangrong Chen, Yasong Li, L. Luo\",\"doi\":\"10.3760/CMA.J.ISSN.1674-635X.2019.02.004\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Objective \\nTo investigate the effects and mechanisms of glutamine(Gln) supplementation on oxidative stress, autophagy response and neurobehavioral outcome after traumatic brain injury (TBI) in rats. \\n \\n \\nMethods \\nTBI animal models were established using Feeney's method. Eighty SD rats were randomly divided into 4 groups: sham operation group (group Sham), Sham + glutamine supplementation group (group Sham+ GLN), traumatic brain injury group (group TBI), and TBI + glutamine supplementation group (group TBI+ GLN). We measured rat behavioral outcomes by modified neurologic severity score (mNSS) tests at day 1, 3, 7 and 14 after TBI. The apoptosis neurons in TBI cerebral cortex were determined by TUNEL staining. The expression of reactive oxygen species (ROS) was tested by ROS kits. Oxidative stress and autophagy related cytokines (HO-1, NQO1, Nrf2, LC3-Ⅱ and Beclin-1) were tested with Western blotting. \\n \\n \\nResults \\nCompared with the TBI group, the neurological function was improved[(9.79±0.43)vs.(8.43±0.30), F=6.775, P=0.010] and the apoptosis rate decreased(19.88% ±1.60% vs. 15.35% ±1.28%, P=0.013) in the TBI+ GLN group after 7-day treatment. Compared with the Sham group, the protein expression of ROS increased(P=0.000), and the expression of anti-oxidative stress factors (HO-1, NQO1) and Nrf2 pathway significantly decreased in the TBI group. After glutamine supplementation was given, the expression of ROS decreased and the expressions of HO-1 and NQO1 increased. The Nrf2 pathway and autophagy response also were activated with the expressions of Nrf2, LC3-Ⅱ and Beclin-1 increasing. \\n \\n \\nConclusion \\nGlutamine supplementation can markedly reduce neuron apoptosis and improve neurological outcomes after TBI, thus has the protective effect on nerves by inhibiting TBI-induced oxidative stress response, activating Nrf2 pathway and autophagy response. \\n \\n \\nKey words: \\nTraumatic brain injury; Glutamine; Oxidative stress; Nrf2 pathway; Autophagy\",\"PeriodicalId\":9877,\"journal\":{\"name\":\"中华临床营养杂志\",\"volume\":\"27 1\",\"pages\":\"84-89\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2019-04-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"中华临床营养杂志\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3760/CMA.J.ISSN.1674-635X.2019.02.004\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"Nursing\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"中华临床营养杂志","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3760/CMA.J.ISSN.1674-635X.2019.02.004","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"Nursing","Score":null,"Total":0}
Neuroprotective effect of glutamine supplementation by inhibiting oxidative stress and promoting autophagy responses after traumatic brain injury in rats
Objective
To investigate the effects and mechanisms of glutamine(Gln) supplementation on oxidative stress, autophagy response and neurobehavioral outcome after traumatic brain injury (TBI) in rats.
Methods
TBI animal models were established using Feeney's method. Eighty SD rats were randomly divided into 4 groups: sham operation group (group Sham), Sham + glutamine supplementation group (group Sham+ GLN), traumatic brain injury group (group TBI), and TBI + glutamine supplementation group (group TBI+ GLN). We measured rat behavioral outcomes by modified neurologic severity score (mNSS) tests at day 1, 3, 7 and 14 after TBI. The apoptosis neurons in TBI cerebral cortex were determined by TUNEL staining. The expression of reactive oxygen species (ROS) was tested by ROS kits. Oxidative stress and autophagy related cytokines (HO-1, NQO1, Nrf2, LC3-Ⅱ and Beclin-1) were tested with Western blotting.
Results
Compared with the TBI group, the neurological function was improved[(9.79±0.43)vs.(8.43±0.30), F=6.775, P=0.010] and the apoptosis rate decreased(19.88% ±1.60% vs. 15.35% ±1.28%, P=0.013) in the TBI+ GLN group after 7-day treatment. Compared with the Sham group, the protein expression of ROS increased(P=0.000), and the expression of anti-oxidative stress factors (HO-1, NQO1) and Nrf2 pathway significantly decreased in the TBI group. After glutamine supplementation was given, the expression of ROS decreased and the expressions of HO-1 and NQO1 increased. The Nrf2 pathway and autophagy response also were activated with the expressions of Nrf2, LC3-Ⅱ and Beclin-1 increasing.
Conclusion
Glutamine supplementation can markedly reduce neuron apoptosis and improve neurological outcomes after TBI, thus has the protective effect on nerves by inhibiting TBI-induced oxidative stress response, activating Nrf2 pathway and autophagy response.
Key words:
Traumatic brain injury; Glutamine; Oxidative stress; Nrf2 pathway; Autophagy
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.