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山东大学学报 (医学版) ›› 2022, Vol. 60 ›› Issue (2): 14-21.doi: 10.6040/j.issn.1671-7554.0.2021.1290

• 基础医学 • 上一篇    下一篇

牛磺酸对1-溴丙烷致大鼠认知功能障碍的保护作用

赵慧文,许琳,单姗,赵秀兰   

  1. 山东大学公共卫生学院卫生毒理与营养学系, 山东 济南 250012
  • 发布日期:2022-01-25
  • 通讯作者: 赵秀兰. E-mail:zhao.xl@sdu.edu.cn
  • 基金资助:
    国家自然科学基金(81872654)

Protective effect of taurine on cognitive deficit induced by 1-bromopropane

ZHAO Huiwen, XU Lin, SHAN Shan, ZHAO Xiulan   

  1. Department of Toxicology and Nutrition, School of Public Health, Shandong University, Jinan 250012, Shandong, China
  • Published:2022-01-25

摘要： 目的 观察牛磺酸对1-溴丙烷致大鼠中枢神经系统功能损伤的保护作用。 方法 SPF级成年雄性Wistar大鼠60只,按体质量随机分为空白对照组、1-溴丙烷染毒组、低剂量牛磺酸干预组、高剂量牛磺酸干预组、牛磺酸对照组。1-溴丙烷采用玉米油稀释,经口染毒,剂量800 mg/kg,染毒15~20 d,采用Morris水迷宫检测大鼠认知功能。实验21 d处死动物,迅速分离大脑皮层及海马,采用高效液相色谱法检测脑组织中牛磺酸含量,采用Western blotting法检测线粒体氧化磷酸化蛋白复合体及凋亡相关蛋白的表达。 结果 Morris水迷宫结果显示,与空白对照组相比,1-溴丙烷染毒组大鼠逃避潜伏期延长,穿越平台次数明显降低(P<0.01);与1-溴丙烷染毒组相比,低剂量和高剂量牛磺酸干预组逃避潜伏期明显缩短,穿越平台次数增加(P<0.01)。HPLC结果显示,与空白对照组相比,1-溴丙烷染毒组大鼠皮层和海马牛磺酸含量明显降低(P<0.001,P<0.05),与1-溴丙烷染毒组相比,低剂量和高剂量牛磺酸干预组大鼠脑组织牛磺酸含量明显升高(P<0.001,P<0.01)。与空白对照组相比,1-溴丙烷染毒组大鼠脑组织中线粒体氧化磷酸化蛋白复合体和Bcl-2表达明显降低(P<0.01,P<0.05),BAX和cleaved caspase-3表达升高(P<0.05,P<0.01);低剂量和高剂量牛磺酸干预组大鼠脑组织线粒体氧化磷酸化蛋白复合体及凋亡相关蛋白的变化趋势有明显逆转,与1-溴丙烷染毒组相比,差异均有统计学意义(P<0.01,P<0.05,P<0.001)。 结论 补充牛磺酸可抑制1-溴丙烷诱导大鼠大脑的神经细胞凋亡,维持大脑线粒体正常功能,进而改善1-溴丙烷致大鼠的认知功能障碍。

关键词: 1-溴丙烷, 牛磺酸, 大鼠, 认知功能障碍

Abstract: Objective To explore the protective effect of taurine on cognitive deficit induced by 1-bromopropane(1-BP). Methods A total of 60 SPF adult male Wistar rats were randomly divided into control group, 1-BP group, low-dose taurine intervention group, high-dose taurine intervention group and taurine control group according to body weight. 1-BP was dissolved in corn oil and orally administrated at the dose of 800 mg/kg.bw. The spatial learning and memory function of rats were detected with Morris water maze(MWM)15-20 days after the administration of 1-BP. On Day 21, the rats were sacrificed and the cerebral cortex and hippocampus were separated immediately. The content of taurine was determined with high-performance liquid chromatography(HPLC). The expressions of oxidative phosphorylation protein complex of mitochondria and apoptosis related proteins in brains were detected with Western blotting. Results Morris water maze showed that compared with the control group, 1-BP group had longer escape latency, and decreased frequencies of crossing platform(P<0.01); compared with 1-BP group, the low-dose and high-dose taurine intervention groups had shorter escape latency and increased frequencies of crossing platform(P<0.01). The HPLC results showed that compared with the control group, the 1-BP group had significantly decreased taurine contents in cerebral cortex and hippocampus(P<0.001, P<0.05); compared with 1-BP group, the low-dose and high-dose taurine intervention groups had significantly increased taurine level(P<0.001, P<0.01). Compared with the control group, the 1-BP group had significantly decreased expression of mitochondrial oxidative phosphorylation protein complex(OXPHOS)and Bcl-2(P<0.01, P<0.05), but significantly increased expressions of BAX and cleaved capase-3(P<0.05, P<0.01). The alteration trends of OXPHOS and apoptosis related proteins in low-dose and high-dose taurine intervention groups were significantly reversed(P<0.01, P<0.05, P<0.001). Conclusion Taurine supplementation could inhibit neuronal apoptosis, maintain the normal function of mitochondria, and improve the learning and memory dysfunction caused by 1-BP.

Key words: 1-bromopropane, Taurine, Rats, Cognitive deficit

中图分类号: 

  • R994.6
[1] 张意. 1-溴丙烷神经毒性作用机制及生物标志研究进展[J]. 卫生研究, 2017, 46(3): 505-508.
[2] Wang TH, Wu ML, Wu YH, et al. Neurotoxicity associated with exposure to 1-bromopropane in golf-club cleansing workers [J]. Clin Toxicol, 2015, 53(8): 823-826.
[3] 李卫华, 王强毅, 市原学, 等. 1-溴丙烷对接触工人神经毒性的剂量-效应关系[J]. 中华劳动卫生职业病杂志, 2010, 28(7): 488-493. LI Weihua, WANG Qiangyi, ICHIHARA Gaku, et al. Exposure to 1-bromopropane causes dose-dependent neurological abnormalities in workers [J]. Chinese Journal of Industrial Hygiene and Occupational Diseases, 2010, 28(7): 488-493.
[4] Kumari N, Prentice H, Wu JY. Taurine and its neuroprotective role [J]. Adv Exp Med Biol, 2013, 775: 19-27. doi:10.1007/978-1-4614-6130-2_2.
[5] Wu JY, Wu H, Jin Y, et al. Mechanism of neuroprotective function of taurine [J]. Adv Exp Med Biol, 2009, 643: 169-179. doi: 10.1007/978-0-387-75681-3_17.
[6] Hernández-Benítez R, Pasantes-Morales H, Salda(~overn)a IT, et al. Taurine stimulates proliferation of mice embryonic cultured neural progenitor cells [J]. J Neurosci Res, 2010, 88(8): 1673-1681.
[7] El Idrissi A, Shen CH, L'amoreaux WJ. Neuroprotective role of taurine during aging [J]. Amino Acids, 2013, 45(4): 735-750.
[8] Wu JY, Prentice H. Role of taurine in the central nervous system [J]. J Biomed Sci, 2010, 17(Suppl 1): S1.
[9] Lambert IH, Kristensen DM, Holm JB, et al. Physiological role of taurine: from organism to organelle [J]. Acta Physiol(Oxf), 2015, 213(1): 191-212.
[10] Vitvitsky V, Garg SK, Banerjee R. Taurine biosynthesis by neurons and astrocytes [J]. J Biol Chem, 2011, 286(37): 32002-32010.
[11] Oja SS, Saransaari P. Open questions concerning taurine with emphasis on the brain [J]. Adv Exp Med Biol, 2015, 803: 409-413. doi: 10.1007/978-3-319-15126-7_31.
[12] Jang H, Lee S, Choi SL, et al. Taurine directly binds to oligomeric amyloid-β and recovers cognitive deficits in Alzheimer model mice [J]. Adv Exp Med Biol, 2017, 975(Pt 1): 233-241. doi: 10.1007/978-94-024-1079-2_21.
[13] 李新娟,葛治国,李东亮,等.牛磺酸对大鼠脑损伤后认知功能及海马凋亡相关蛋白表达的影响[J]. 新乡医学院学报, 2006, 23(6): 569-571. LI Xinjuan, GE Zhiguo, LI Dongliang, et al. Effect of taurine on the cognitive function and the expression of protein related apoptosis in hippocampus after diffuse brain injury in rats [J]. Journal of Xinxiang Medical College, 2006, 23(6): 569-571.
[14] Wang K, Shi Y, Liu W, et al. Taurine improves neuron injuries and cognitive impairment in a mouse Parkinsons disease model through inhibition of microglial activation [J]. Neurotoxicology, 2021, 83: 129-136. doi: 10.1016/j.neuro.2021.01.002.
[15] Jakaria M, Azam S, Haque ME, et al. Taurine and its analogs in neurological disorders: Focus on therapeutic potential and molecular mechanisms [J]. Redox Biol, 2019, 24: 101223. doi: 10.1016/j.redox.2019.
[16] Xu Y, Wang S, Jiang L, et al. Identify melatonin as a novel therapeutic reagent in the treatment of 1-bromopropane(1-BP)intoxication [J]. Medicine(Baltimore), 2016, 95(3): e2203.
[17] Suo JN, Zhang CL, Wang P, et al. Allyl sulfide counteracts 1-bromopropane-induced neurotoxicity by inhibiting neuroinflammation and oxidative stress [J]. Toxicol Sci, 2019, 167(2): 397-407.
[18] Yang G, Xiang Y, Zhou W, et al. 1-Bromopropane-induced apoptosis in OVCAR-3 cells via oxidative stress and inactivation of Nrf2 [J]. Toxicol Ind Health, 2021, 37(2): 59-67.
[19] Castellanos E, Lanning NJ. Phosphorylation of OXPHOS machinery subunits: functional implications in cell biology and disease [J]. Yale J Biol Med, 2019, 92(3): 523-531.
[20] 徐建兴. 呼吸链的电子漏路径和线粒体的超氧自由基代谢及其生物学意义[J]. 基础医学与临床, 2001, 21(5): 389-394. XU Jianxing. Electronleak of respiratory chain and the metabolism of superoxide anion in mitochondria [J]. Basic Medical Sciences and Clinics, 2001, 21(5): 389-394.
[21] Cheng L, Chen L, Wei X, et al. NOD2 promotes dopaminergic degeneration regulated by NADPH oxidase 2 in 6-hydroxydopamine model of Parkinson's disease [J]. J Neuroinflammation, 2018, 15(1): 243.
[22] Han Z, Gao LY, Lin YH, et al. Neuroprotection of taurine against reactive oxygen species is associated with inhibiting NADPH oxidases [J]. Eur J Pharmacol, 2016, 777: 129-135. doi: 10.1016/j.ejphar.2016.03.006.
[23] Jong CJ, Azuma J, Schaffer S. Mechanism underlying the antioxidant activity of taurine: prevention of mitochondrial oxidant production [J]. Amino Acids, 2012, 42(6): 2223-2232.
[24] Baydas G, Reiter RJ, Akbulut M, et al. Melatonin inhibits neural apoptosis induced by homocysteine in Hippocampus of rats via inhibition of cytochrome c translocation and caspase-3 activation and by regulating pro- and anti-apoptotic protein levels [J]. Neuroscience, 2005, 135(3): 879-886.
[25] Yalçinkaya S, Unlüçerçi Y, Giri?瘙塂 M, et al. Oxidative and nitrosative stress and apoptosis in the liver of rats fed on high methionine diet: protective effect of taurine [J]. Nutrition, 2009, 25(4): 436-444.
[26] Leon R, Wu H, Jin Y, et al. Protective function of taurine in glutamate-induced apoptosis in cultured neurons [J]. J Neurosci Res, 2009, 87(5): 1185-1194.
[27] Taranukhin AG, Taranukhina EY, Saransaari P, et al. Neuroprotection by taurine in ethanol-induced apoptosis in the developing cerebellum J]. J Biomed Sci, 2010, 17(Suppl 1): S12.
[28] Niu XL, Zheng SM, Liu HT, et al. Protective effects of taurine against inflammation, apoptosis, and oxidative stress in brain injury [J]. Mol Med Rep, 2018, 18(5): 4516-4522.
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