北京生物醫(yī)學(xué)工程

運(yùn)動(dòng)對(duì)大鼠慢性高眼壓視網(wǎng)膜自噬與凋亡的影響

Effects of training on retinal autophagy and apoptosis in rats with chronic ocular hypertension

作者：龍曉雪楊宏宇薛艷麗宋紅芳

單位：首都醫(yī)科大學(xué) 生物醫(yī)學(xué)工程學(xué)院（北京 100069）臨床生物力學(xué)應(yīng)用基礎(chǔ)研究北京市重點(diǎn)實(shí)驗(yàn)室（北京 100069）

關(guān)鍵詞：慢性高眼壓；運(yùn)動(dòng)訓(xùn)練；視網(wǎng)膜；自噬；凋亡

分類號(hào)：R318

出版年·卷·期（頁碼）：2021·40·3（239-244）

摘要：

目的探討在慢性高眼壓作用下，中輕度運(yùn)動(dòng)訓(xùn)練對(duì)大鼠視網(wǎng)膜細(xì)胞自噬與凋亡水平的影響，尋找利于修復(fù)慢性高眼壓造成視網(wǎng)膜損傷的適宜運(yùn)動(dòng)強(qiáng)度。方法選取接受運(yùn)動(dòng)預(yù)訓(xùn)練的8周齡SD雄性大鼠32只，隨機(jī)平均分為空白對(duì)照（control, C）組、中度訓(xùn)練（moderate intensity training, MT）組、輕度訓(xùn)練（low intensity training, LT）組和靜置實(shí)驗(yàn)高眼壓（experimental glaucoma, GL）組4組，每組各8只。C組不做任何處理，對(duì)MT、LT、GL組采用烙閉鞏膜上靜脈的方法建立慢性高眼壓大鼠模型；對(duì)MT、LT組進(jìn)行3周運(yùn)動(dòng)干預(yù)，每次分別以23 m/min（約70% VO2max）和17 m/min（約58% VO2max）的強(qiáng)度持續(xù)跑步60 min，每日訓(xùn)練1次，每周訓(xùn)練5日，而GL組靜置處理相同時(shí)間。之后取大鼠視網(wǎng)膜組織，用NeuN標(biāo)記神經(jīng)節(jié)細(xì)胞，TUNEL標(biāo)記凋亡細(xì)胞，并檢測細(xì)胞自噬相關(guān)蛋白LC3、Beclin1及細(xì)胞凋亡相關(guān)蛋白Bax、Bcl-xL的表達(dá)。結(jié)果 MT、LT組的視網(wǎng)膜細(xì)胞自噬與凋亡水平均低于GL組，表現(xiàn)在LC3、Beclin1、Bax蛋白表達(dá)下調(diào)，Bcl-xl蛋白表達(dá)上調(diào)，TUNEL陽性細(xì)胞數(shù)減少，神經(jīng)節(jié)細(xì)胞（RGCs）數(shù)量明顯保留；而MT組與LT組之間無明顯差異。結(jié)論 3周的中輕度訓(xùn)練均可以下調(diào)慢性高眼壓造成的視網(wǎng)膜神經(jīng)節(jié)細(xì)胞的自噬與凋亡水平，但兩種運(yùn)動(dòng)強(qiáng)度沒有明顯差異，說明中輕度訓(xùn)練均有利于修復(fù)慢性高眼壓造成的視網(wǎng)膜損傷。

Objective To investigate the effects of moderate and low intensity training on retinal autophagy and apoptosis in rats with chronic ocular hypertension, and to explore the appropriate exercise intensity to repair retinal injury caused by chronic ocular hypertension. Methods Thirty-two 8-week-old SD male rats pre-trained were randomly divided into 4 groups: Control (C) group (n = 8), Moderate Intensity Training (MT) group (n = 8), Low Intensity Training (LT) group (n = 8), and Experimental Glaucoma (GL) group (n = 8). Group C did not receive any treatment; groups MT, LT and GL underwent cauterization of superior scleral veins to construct chronic ocular hypertension models. The groups MT and LT were treated with exercise intervention for 3 weeks, with respectively the intensity of 23m/min (about 70% VO2max) and 17m/min (about 58% VO2max) continuous running for 60 min, once a day and 5 days a week. Group GL was untreated for the same time. After the training, the retinal tissues of rats were collected, the RGCs were labeled by NeuN and apoptotic cells were labeled by TUNEL. The expressions of autophagy-related proteins LC3 and Beclin1, as well as apoptotic proteins Bax and Bcl-xl were detected. Results After 3 weeks of exercise, the levels of retinal autophagy and apoptosis in groups MT and LT were lower than those in group GL, which demonstrated that the expressions of LC3, Beclin1 and Bax were down-regulated, the expression of Bcl-xl was up-regulated, the number of TUNEL positive cells was decreased, and the number of RGCs was retained significantly. However, there was no significant difference between group MT and group LT. Conclusions The autophagy and apoptosis levels of RGCs induced by chronic ocular hypertension were decreased by both moderate and low intensity trainings for 3 weeks, and there was no significant difference between the two types of training intensity, indicating that both moderate and low training were beneficial to repair retinal injury caused by chronic ocular hypertension.

參考文獻(xiàn)：

[1]黨鴻, 辛?xí)匀? 青光眼視神經(jīng)損傷機(jī)制的研究進(jìn)展[J]. 眼科新進(jìn)展, 2016, 36(7):680-683.

Dang?H, Xin?XR. Research progress on optic nerve impairment mechanism in glaucoma[J]. Recent Advances in Ophthalmology, 2016, 36(7):680-683.

[2]?陳琛, 劉曉華. 青光眼相關(guān)生物力學(xué)研究進(jìn)展[J]. 北京生物醫(yī)學(xué)工程, 2007, 26(1):92-94.

Chen C,?Liu XH. The progression of the biomechanicai study on glaucoma[J]. Beijing Biomedical Engineering,?2007, 26(1):92-94.?

[3]?Maiuri MC, Zalckvar E, Kimchi A, et al. Self-eating and self-killing: crosstalk between autophagy and apoptosis[J]. Nature Reviews Molecular?Cell?Biology, 2007, 8(9): 741-752.

[4]?Deng?S, Wang M, Yan Z, et al. Autophagy in Retinal Ganglion Cells in a Rhesus Monkey Chronic Hypertensive Glaucoma Model[J]. Plos One, 2013, 8(10): 1-12.

[5]?Park HYL, Kim JH, Park CK. Activation of autophagy induces retinal ganglion cell death in a chronic hypertensive glaucoma model[J]. Cell Death & Disease, 2012, 3(4): 1-9.

[6]?Zoladz JA, Pilc A. The effect of physical activity on the brain derived neurotrophic factor: from animal to human studies[J]. Journal of physiology & pharmacology an official journal of the polish physiological society, 2010, 61(5): 533-541.

[7]?Li HY, Rong SS, Hong X, et al. Exercise and retinal health[J]. Restorative neurology and neuroscience, 2019, 37, (6): 571-581.

[8]?Chrysostomou V, Galic S, Van Wijngaarden P, et al. Exercise reverses age-related vulnerability of the retina to injury by preventing complement-mediated synapse elimination via a BDNF-dependent pathway[J]. Aging Cell, 2016, 15: 1082-1091.

[9]?Chrysostomou V, Kezic JM, Trounce I A, et al. Forced exercise protects the aged optic nerve against intraocular pressure injury[J]. Neurobiology of Aging, 2014, 35(7): 1722-1725.

[10]?Lawson EC, Han MK, Sellers JT, et al. Aerobic exercise protects retinal function and structure from light-induced retinal degeneration[J]. Journal of Neuroscience, 2014, 34(7): 2406-2412.

[11]?Chrenek MA, Sellers JT, Lawson EC, et al. Exercise and cyclic light preconditioning protect against light-induced retinal degeneration and evoke similar gene expression patterns[J]. Advances in Experimental Medicine & Biology, 2016, 854: 443-448.

[12]?Kim J. Treadmill exercise ameliorates apoptotic cell death in the retinas of diabetic rats[J]. Molecular Medicine Reports, 2013, 7(6): 1745-1750.

[13]?Allen RS, Hanif AM, Gogniat MA, et al. TrkB signaling pathway mediates the protective effects of exercise in the diabetic rat retina[J]. European Journal of Neuroscience, 2018, 47(10): 1-29.

[14]?賈紹輝, 劉君, 寇現(xiàn)娟, 等. 運(yùn)動(dòng)誘導(dǎo)的細(xì)胞自噬對(duì)小鼠心肌的保護(hù)作用[J]. 武漢體育學(xué)院學(xué)報(bào), 2014, 48(10): 53-56.

Jia SH, Liu J, Kou XJ, et al. Protective role of exercise -induced autophagy in myocardial cells of mice[J]. Journal of Wuhan Institute of Physical Education, 2014,?48(10): 53-56.

[15]Mejías-Pea Y, Estébanez B, Rodriguez-Miguelez P, et al. Impact of resistance training on the autophagy-inflammation-apoptosis crosstalk in elderly subjects[J]. Aging, 2017, 9(2): 408-418.

[16]Kwon I, Song W, Jang Y, et al. Elevation of hepatic autophagy and antioxidative capacity by endurance exercise is associated with suppression of apoptosis in mice[J]. Annals of hepatology: official journal of the Mexican Association of Hepatology, 2019, 19(1): 69-78.

[17]Zhang L. Physical exercise improves functional recovery through mitigation of autophagy, attenuation of apoptosis and enhancement of neurogenesis after MCAO in rats[J]. BMC Neuroscience, 2013, 14(46): 1-8.

[18]?Lee Y, Kim J H, Hong Y, et al. Prophylactic effects of swimming exercise on autophagy-induced muscle atrophy in diabetic rats[J]. Laboratory Animal Research, 2012, 28(3): 171-179.

[19]?GA Brooks, T P White. Determination of metabolic and heart rate responses of rats to treadmill exercise[J]. Journal of Applied Physiology Respiratory Environmental & Exercise Physiology, 1978, 45(6):?1009-1015.

[20]?Bedford T G, Tipton C M, Wilson N C, et al. Maximum oxygen consumption of rats and its changes with various experimental procedures[J]. Journal of Applied Physiology Respiratory Environmental & Exercise Physiology, 1979, 47(6): 1278-1283.

[21]?Thom W M, John D, Geralyn P,?et al. Retinal damage after 3 to 4 months of elevated intraocular pressure in a rat glaucoma model[J].??Investigative Ophthalmology and Visual Science, 2000, 41(11):?3451-3459.

[22]?鄭園園, 李洋, 程艷麗. 運(yùn)動(dòng)對(duì)自噬相關(guān)因子影響的研究進(jìn)展[J]. 當(dāng)代醫(yī)學(xué), 2019, 25(03):192-194.

[23]?田凈凈. 自噬在青光眼發(fā)生和發(fā)展中的作用[J]. 中華實(shí)驗(yàn)眼科雜志, 2020, 38(5):442-446.

Tian JJ. Role of autophagy in the occurrence and development of glaucoma[J]. Chinese Journal of Experimental Ophthalmology, 2020, 38(5):442-446.

[24]?Phatak NR, Stankowska DL, Krishnamoorthy RR. Bcl-2, Bcl-xL, and p-AKT are involved in neuroprotective effects of transcription factor Brn3b in an ocular hypertension rat model of glaucoma[J]. Molecular Vision, 2016, 22: 1048-1061.

[25]?金丹, 楊劍, 孫怡寧,等. 運(yùn)動(dòng)鍛煉對(duì)慢性阻塞性肺疾病患者肺康復(fù)的干預(yù)效果[J]. 北京生物醫(yī)學(xué)工程, 2017, 36(5):540-544.

Jin?D, Yang?J, Sun?YN, et al. Effect of exercise intervention for pulmonary rehabilitation in patients with chronic obstructive pulmonary disease[J]. Beijing Biomedical Engineering,?2017, 36(5):540-544.

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