Effect of Suanzaoren Tang on Mitochondrial Damage and Apoptosis in Hypothalamus of Elderly Rats with Chronic Rapid Eye Movement Sleep Deprivation

Min-min YANG; Xin LIU; Qiu-yun YOU; Shun-bo ZHANG

doi:10.13422/j.cnki.syfjx.20211304

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Effect of Suanzaoren Tang on Mitochondrial Damage and Apoptosis in Hypothalamus of Elderly Rats with Chronic Rapid Eye Movement Sleep Deprivation

Study on Treatment of Senile Chronic Sleep Deprivation Rats with Suanzaoren Tang | 更新时间：2021-07-20

- Effect of Suanzaoren Tang on Mitochondrial Damage and Apoptosis in Hypothalamus of Elderly Rats with Chronic Rapid Eye Movement Sleep Deprivation
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 27, Issue 16, Pages: 47-52(2021)
- 作者机构：
  
  湖北中医药大学，武汉 430065
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20211304
  CLC： R2-0;R22;R285.5;R289;R33
- Received：16 February 2021，
  
  Published Online：20 May 2021，
  
  Published：20 August 2021
- 稿件说明：
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杨忞旻,刘鑫,游秋云等.酸枣仁汤对老年慢性快动眼睡眠剥夺模型大鼠中枢下丘脑线粒体损伤及细胞凋亡的影响[J].中国实验方剂学杂志,2021,27(16):47-52.

YANG Min-min,LIU Xin,YOU Qiu-yun,et al.Effect of Suanzaoren Tang on Mitochondrial Damage and Apoptosis in Hypothalamus of Elderly Rats with Chronic Rapid Eye Movement Sleep Deprivation[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(16):47-52.
杨忞旻,刘鑫,游秋云等.酸枣仁汤对老年慢性快动眼睡眠剥夺模型大鼠中枢下丘脑线粒体损伤及细胞凋亡的影响[J].中国实验方剂学杂志,2021,27(16):47-52. DOI： 10.13422/j.cnki.syfjx.20211304.

YANG Min-min,LIU Xin,YOU Qiu-yun,et al.Effect of Suanzaoren Tang on Mitochondrial Damage and Apoptosis in Hypothalamus of Elderly Rats with Chronic Rapid Eye Movement Sleep Deprivation[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(16):47-52. DOI： 10.13422/j.cnki.syfjx.20211304.

摘要

目的

探讨酸枣仁汤对线粒体介导的神经细胞凋亡的影响。

方法

将50只雄性Wistar大鼠随机分为正常组、模型组、舒乐安定组（0.18 mg·kg

-1

·d

-1

），酸枣仁汤低、高剂量组（6.48，12.96 g·kg

-1

·d

-1

），除正常组外，其余各组均皮下注射

-半乳糖，于末次给药后进行多平台水环境睡眠剥夺，造模结束后各组开始灌胃给药，连续给药7 d。采用透射电镜观察中枢下丘脑线粒体形态，采用分光光度法检测检测中枢下丘脑中Na

-K

-三磷酸腺苷（ATP）酶，Ca

-Mg

-ATP酶活性，蛋白免疫印迹法（Western blot）检测中枢下丘脑细胞色素C（Cyt C），B细胞淋巴瘤-2（Bcl-2），Bcl-2相关X蛋白（Bax）及半胱氨酸天冬氨酸蛋白水解酶-3（Caspase-3）蛋白表达水平的改变。

结果

正常组线粒体未见明显病理改变，大小适中，形态多呈椭圆或梭形，嵴排列较整齐。与正常组比较，模型组线粒体形态异常，线粒体发生明显肿胀并且伴有空泡化，出现了“髓鞘样”，嵴发生断裂且数量减少；与模型组比较，舒乐安定组、酸枣仁汤高剂量组线粒体损伤减轻，空泡化现象减少，部分嵴断裂，并未出现明显肿胀，其中酸枣仁汤高剂量组改善较为明显。与正常组比较，模型组Na

-K

-ATP，Ca

-Mg

-ATP酶活性显著降低（

0.01），Bcl-2蛋白表达水平显著降低（

0.01），Cyt C，Bax，Caspase-3蛋白表达水平显著升高（

0.01）；与模型组比较，舒乐安定组、酸枣仁汤高剂量组Na

-K

-ATP，Ca

-Mg

-ATP酶活性均显著升高（

0.01），舒乐安定组、酸枣仁汤高剂量组Bcl-2蛋白表达水平显著升高（

0.01），Cyt C，Bax，Caspase-3蛋白表达水平明显降低（

0.05，

0.01），酸枣仁汤低剂量组Na

-K

-ATP酶活性显著升高（

0.01），Bcl-2蛋白表达水平明显升高（

0.05），Bax蛋白表达水平明显降低（

0.05）。

结论

酸枣仁汤可以改善下丘脑神经细胞线粒体功能，抑制神经细胞凋亡。

Abstract

Objective

To investigate the effect of Suanzaoren Tang on mitochondria-mediated neuronal apoptosis.

Method

Fifty male Wistar rats were randomly divided into the control group， model group， estazolam group （0.18 mg·kg

-1

·d

-1

）， and low- （6.48 g·kg

-1

·d

-1

） and high-dose （12.96 g·kg

-1

·d

-1

） Suanzaoren Tang groups. Rats in all groups except for the control group received subcutaneous injection of

-galactose and then were deprived of sleep using the multiple platform method after the last administration. Following successful modeling， the rats in each group were treated with intragastric administration of the corresponding drugs for seven consecutive days. The morphology of mitochondria in hypothalamus was observed under a transmission electron microscope. The activities of Na

-K

-ATPase and Ca

-Mg

-ATPase in hypothalamus were detected by spectrophotometry. Western blotting was conducted to determine the protein expression levels of cytochrome C （Cyt C）， B cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax） and cysteinyl aspartate-specific protease-3 （Caspase-3） in hypothalamus.

Result

In the control group， there was no obvious pathological change in mitochondria， which were moderate in size and oval or spindle in shape， with the cristae arranged orderly. Compared with the control group， the model group exhibited abnormal mitochondrial morphology， manifested as obvious swelling， vacuolation， myelin figures， and cristae rupture and reduction. The comparison with the model group revealed that both the estazolam group and high-dose Suanzaoren Tang group alleviated the mitochondrial damage and reduced the vacuolation and swelling. Only some cristae rupture was present. The improvements were more obvious in the high-dose Suanzaoren Tang group. Compared with the control group， the activities of Na

-K

-ATPase and Ca

-Mg

-ATPase and the Bcl-2 protein expression in the model group were significantly decreased （

0.01）， whereas the protein expression levels of Cyt C， Bax， and Caspase-3 were significantly increased （

0.01）. Compared with the model group， the activities of Na

-K

-ATPase and Ca

-Mg

-ATPase and the Bcl-2 protein expression in the estazolam group and the high-dose Suanzaoren Tang group were significantly elevated （

0.01）， while the protein expression levels of Cyt C， Bax， and Caspase-3 were significantly lowered （

0.05，

0.01）. The activity of Na

-K

-ATPase and the Bcl-2 protein expression in the low-dose Suanzaoren Tang group were increased significantly （

0.01）， but the Bax protein expression was down-regulated （

0.05）.

Conclusion

Suanzaoren Tang is able to improve the mitochondrial function of hypothalamic nerve cells and inhibit their apoptosis.

关键词

Keywords

references

APPLETON S ， GILL T ， LANG C ， et al . Prevalence and comorbidity of sleep conditions in Australian adults：2016 Sleep Health Foundation national survey ［J］. Sleep Health ， 2018 ， 4 （ 1 ）： 13 - 19 .

KUWAHARA K ， IMAI T ， MIYAMOTO T ， et al . Sleep duration modifies the association of overtime work with risk of developing type 2 diabetes：Japan epidemiology collaboration on occupational health study ［J］. J Epidemiol ， 2018 ， 28 （ 7 ）： 336 - 340 .

WHEATON A ， JONES S ， COOPER A ， et al . Short sleep duration among middle school and high school students-united states 2015 ［J］. Morb Mortal Wkly Rep ， 2018 ， 67 （ 3 ）： 85 - 90 .

黄晓宇，谢光璟，黄攀攀 . 天王补心丹加减干预睡眠剥夺大鼠能量代谢机制的生物信息学分析［J］. 中国实验方剂学杂志， 2020 ， 26 （ 22 ）： 172 - 180 .

吴东南，丁瑞丛，纪可，等 . 酸枣仁汤对慢性睡眠剥夺大鼠学习记忆及TLR4/NF- κ B信号通路的影响［J］. 中国实验方剂学杂志， 2020 ， 26 （ 6 ）： 18 - 24 .

王玉，杨雪，夏鹏飞，等 . 酸枣仁汤化学成分、药理作用、临床应用的研究进展及质量标志物的预测分析［J］. 中国中药杂志， 2020 ， 45 （ 12 ）： 2765 - 2771 .

张舜波，王平，田代志，等 . 酸枣仁总皂苷对失眠老年大鼠脑氨基酸类神经递质及受体表达的影响［J］. 中国实验方剂学杂志， 2014 ， 20 （ 4 ）： 124 - 127 .

张如意，游秋云，王平，等 . 酸枣仁汤对慢性睡眠剥夺老年失眠大鼠视交叉上核c-fos及nNos表达的影响［J］. 辽宁中医杂志， 2017 ， 44 （ 10 ）： 2211 - 2213，2243 .

张如意 . 酸枣仁汤对基于5HTR调控老年失眠SCN及VLPO系统的作用及机制研究［D］. 武汉：湖北中医药大学， 2017 .

张如意，游秋云，王平，等 . 酸枣仁汤对慢性睡眠剥夺老年失眠大鼠心肌细胞凋亡及相关蛋白Bcl2、Bax表达的影响［J］. 中华中医药杂志， 2017 ， 32 （ 4 ）： 1691 - 1693 .

赵凡凡，周玉枝，高丽，等 . D -半乳糖致衰老大鼠模型的研究进展［J］. 药学学报， 2017 ， 52 （ 3 ）： 347 - 354 .

徐智，吴国明，钱桂生，等 . 大鼠衰老模型的初步建立［J］. 第三军医大学学报， 2003 ， 25 （ 4 ）： 312 - 315 .

宾东华，何清湖，韩忠，等 . 知柏地黄汤对解脲脲原体感染模型大鼠精子线粒体Na + -K + -ATP酶及Ca 2+ -Mg 2+ -ATP酶活性的影响［J］. 中华中医药杂志， 2017 ， 32 （ 4 ）： 1528 - 1531 .

范颖，李楠，孙云峰，等 . 黄芪有效部位对糖尿病大鼠Na + -K + -ATP酶活性及AMPK蛋白表达的影响［J］. 中华中医药杂志， 2012 ， 27 （ 10 ）： 2660 - 2663 .

苑春元，周华，戎靖枫，等 . 补心方对慢性心衰大鼠心肌Na + -K + ATP酶、Ca 2+ -Mg 2+ ATP酶及琥珀酸脱氢酶的作用研究［J］. 时珍国医国药， 2013 ， 24 （ 6 ）： 1374 - 1376 .

翟艺宗，黄昌林，常祺，等 . 中频脉冲电流经皮刺激肝区对运动性疲劳大鼠肝细胞线粒体Na + -K + -ATP酶及Ca 2+ -Mg 2+ -ATP酶活性的影响［J］. 解放军医学杂志， 2015 ， 40 （ 4 ）： 327 - 330 .

徐炜棉，郭金莲，王燕琴，等 . 苦参碱对阿霉素所致H9c2心肌细胞损伤的保护作用及与线粒体Na + -K + -ATP酶、Ca 2+ -ATP酶关系的研究［J］. 中国医院药学杂志， 2019 ， 39 （ 9 ）： 941 - 944 .

李帅，张炳东 . 细胞凋亡途径的研究进展［J］. 山东医药， 2017 ， 57 （ 37 ）： 103 - 106 .

MAURYA S R ， MAHALAKSHMI R . Mitochondrial VDAC2 and cell homeostasis：highlighting hidden structural fea tures and unique functionalities ［J］. Biol Rev Camb Philos Soc ， 2017 ， 92 （ 4 ）： 1843 - 1858 .

YANG Y Y ， YU Y B ， WANG J H ， et al . Silica nanoparticles induced intrinsic apoptosis in neuroblastoma SH-SY5Y cells via Cyt C/Apaf-1 pathway ［J］. Environ Toxicol Phar ， 2017 ， 52 ： 161 - 169 .

OLTERSDORF T ， ELMORE S W ， SHOEMAKER A R ， et al . An inhibitor of Bcl-2 family proteins induces regression of solid tumours ［J］. Nature ， 2005 ， 435 （ 7042 ）： 677 - 681 .

汪枫，喻小兰，夏纪毅，等 . 黄芩素、LY294002对人肝癌细胞系SMMC-7721细胞增殖及凋亡的影响［J］. 山东医药， 2016 ， 56 （ 41 ）： 1 - 5 .

LUO J ， YU L ， XIE G ， et al . Study on the mitochondrial apoptosis pathways of small cell lung cancer H446 cells induced by Trichinella spiralis muscle larvae ESPs ［J］. Parasitology ， 2017 ， 144 （ 6 ）： 1 - 8 .

JIANG W ， CHEN Y ， LI B ， et al . DBA-induced caspase-3-dependent apoptosis occurs through mitochondrial tra nslocation of Cyt-c in rat hippocampus ［J］. Mol Bio Syst ， 2017 ， 13 （ 9 ）： 1863 - 1873 .

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Related Institution

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