左卡尼汀经β-catenin信号通路保护环磷酰胺所致大鼠睾丸损伤

曾鹏, 祁蕊, 王锦, 孙潇, 代佑果, 张鹏飞, 杨力, 郭泽云

中国临床解剖学杂志 ›› 2020, Vol. 38 ›› Issue (3) : 283-288.

中国临床解剖学杂志 ›› 2020, Vol. 38 ›› Issue (3) : 283-288. DOI: 10.13418/j.issn.1001-165x.2020.03.009
实验研究

左卡尼汀经β-catenin信号通路保护环磷酰胺所致大鼠睾丸损伤

  • 曾鹏1, 祁蕊1, 王锦1, 孙潇1, 代佑果2, 张鹏飞1, 杨力1, 郭泽云1
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Protective effects of L-carnitine on testicular injury induced by cyclophosphamide in rats through β-catenin signaling

  • ZENG Peng1,QI Rui1,WANG Jin1,SUN Xiao1,DAI You-guo2,ZHANG Peng-fei1,YANG Li1,GUO Ze-yun1
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摘要

目的 探讨左卡尼汀(L-carnitine,LC)对环磷酰胺(cyclophosphamide,CP)所致大鼠睾丸损伤的保护作用及其机制。  方法 将18只雄性大鼠随机分为3组:生理盐水(NS)组,CP组,CP+LC组,腹腔注射给药。观测大鼠体重、精神等一般情况及睾丸重量,采用HE染色检测睾丸损伤情况,免疫组化和Western blot法检测睾丸内β-catenin的表达。  结果 CP组大鼠睾丸重量低于NS组(P<0.05),CP+LC组大鼠睾丸重量比CP组有所恢复(P<0.05);HE染色显示CP组和CP+LC组比NS组生精细胞层数减少(P<0.05),但CP+LC组较CP组生精细胞层数增多(P<0.05);免疫组化和Western blot均显示CP组β-catenin的表达量高于NS组(P<0.05),CP+LC组β-catenin表达量低于CP组(P<0.05)。  结论 左卡尼汀可下调β-catenin信号进而对环磷酰胺所致大鼠睾丸损伤起到保护作用,可能对抗瘤药引起的男性生育障碍具有潜在的治疗意义。

Abstract

Objective To investigate the protective effects and possible mechanisms of L-carnitine (LC) on cyclophosphamide (CP) induced testicular injury in rats. Methods Eighteen male rats were randomly divided into three groups and received intraperitoneal injection of appropriate drug(a Normal saline group, a CP group, a CP+LC group).  General conditions, weight and testicular weight of rats were recorded. The testicular injury condition was detected by HE staining, and the expression of β-catenin in testis was detected by immunohistochemistry and western blotting. Results The testicular weight in the CP group was lower than that of the NS group(P<0.05). While the testicular weight recovered in the CP+LC group(P<0.05). HE staining result showed that the number of spermatogenic cell layers in CP group decreased significantly than that of the NS group(P<0.05), but the number of spermatogenic cell layers of the CP+LC group was higher than that of the CP group(P<0.05). Immunohistochemistry and Western blot result showed that the expression of β-catenin in the CP group was higher than that of the NS group(P<0.05)while the expression of β-catenin in the CP+LC group was lower than that of the CP group(P<0.05).    Conclusions    L-carnitine can protect testicular injury in rats which induced by Cyclophosphamide through down-regulated β-catenin signaling, which makes a potential therapeutic significance for male fertility disorder caused by antitumor drugs.

关键词

左卡尼汀 /  环磷酰胺 /  睾丸 /  β-catenin

Key words

  / L-carnitine /  Cyclophosphamide /  Testis /  β-catenin

引用本文

导出引用
曾鹏, 祁蕊, 王锦, 孙潇, 代佑果, 张鹏飞, 杨力, 郭泽云. 左卡尼汀经β-catenin信号通路保护环磷酰胺所致大鼠睾丸损伤[J]. 中国临床解剖学杂志. 2020, 38(3): 283-288 https://doi.org/10.13418/j.issn.1001-165x.2020.03.009
ZENG Peng, QI Rui, WANG Jin, SUN Xiao, DAI You-guo, ZHANG Peng-fei, YANG Li, GUO Ze-yun. Protective effects of L-carnitine on testicular injury induced by cyclophosphamide in rats through β-catenin signaling[J]. Chinese Journal of Clinical Anatomy. 2020, 38(3): 283-288 https://doi.org/10.13418/j.issn.1001-165x.2020.03.009
中图分类号: R453.9    

参考文献

[1]  Jodar M, Soler-Ventura A, Oliva R, et al. Semen proteomics and male infertility[J]. J Proteomics, 2017, 162: 125-134. 
[2]  Levine H, Jøorgensen N, Martino-Andrade A, et al. Temporal trends in sperm count: a systematic review and meta-regression analysis[J]. Hum Reprod Update, 2017, 23(6): 646-659.
[3] Ibtisham F, Wu J, Xiao M, et al. Progress and future prospect of spermatogenesis[J]. Oncotarget, 2017, 8(39): 66709-66727.
[4] Micic S, Lalic N, Djordjevic D, et al. Double-blind, randomised, placebo-controlled trial on the effect of L-carnitine and L-acetylcarnitine on sperm parameters in men with idiopathic oligoasthenozoospermia[J]. Andrologia, 2019, 51(6): e13267.
[5]  Topcu-Tarladacalisir Y, Kanter M, Uzal MC. Role of L-carnitine in the prevention of seminiferous tubules damage induced by gamma radiation: a light and electron microscopic study[J]. Arch Toxicol, 2009, 83(8): 735-746.
[6]  陈玲燕, 王雪丁, 黄民. 环磷酰胺的药物基因组学研究进展[J]. 药学学报, 2014, 49(7): 971-976.
[7]  杨群芳. 环磷酰胺对雄性生殖系统毒性损伤的研究进展[J]. 儿科药学杂志, 2013, 19(3): 62-65.
[8] Ceribaşi AO, Türk G, Sönmez M, et al. Toxic effect of cyclophosphamide on sperm morphology, testicular histology and blood oxidant-antioxidant balance, and protective roles of lycopene and ellagic acid[J]. Basic Clin Pharmacol Toxicol, 2010, 107(3): 730-736.
[9]  Aghaie S, Nikzad H, Mahabadi JA, et al. Protective effect of combined pumpkin seed and ginger extracts on sperm characteristics, biochemical parameters and epididymal histology in adult male rats treated with cyclophosphamide[J]. Anat Sci Int, 2016, 91(4): 382-390.
[10] Kumar S, Žigman M, Patel TR, et al. Molecular dissection of Wnt3a-Frizzled8 interaction reveals essential and modulatory determinants of Wnt signaling activity[J]. BMC Biol 2014, 12(1): 44.
[11] Miller JR, Hocking AM, Brown JD. Mechanism and function of signal transduction by the Wnt/beta-catenin and Wnt/Ca2+ pathways[J]. Oncogene, 1999, 18(55): 7860-7872.
[12] Lombardi AP, Royer C, Pisolato R, et al. Physiopathological aspects of the Wnt/β-catenin signaling pathway in the male reproductive system[J]. Spermatogenesis, 2013, 3(1): e23181.
[13] Kerr GE, Young JC, Horvay K, et al. Regulated Wnt/beta-catenin signaling sustains adult spermatogenesis in mice[J]. Biol Reprod, 2014, 90(1): 3.
[14]Chang YF, Lee-Chang JS, Harris KY, et al. Role of β-catenin in post-meiotic male germ cell differentiation[J]. PLoS One, 2011, 6(11): e28039.
[15]Kimura T, Nakamura T, Murayama K, et al. The stabilization of beta-catenin leads to impaired primordial germ cell development via aberrant cell cycle progression[J]. Dev Biol, 2006, 300(2): 545-553.
[16]Zheng B, Yu J, Guo Y, et al. Cellular nucleic acid-binding protein is vital to testis development and spermatogenesis in mice[J]. Reproduction, 2018, 156(1): 59-69.
[17] Chawengsaksophak K, Svingen T, Ng ET, et al. Loss of Wnt5a disrupts primordial germ cell migration and male sexual development in mice[J]. Biol Reprod, 2012, 86(1): 1-12.
[18] Dong WL, Tan FQ, Yang WX. Wnt signaling in testis development: unnecessary or essential[J]? Gene, 2015, 565(2): 155-165.
[19] Kumar M, Atkins J, Cairns M, et al. Germ cell-specific sustained activation of Wnt signalling perturbs spermatogenesis in aged mice, possibly through non-coding RNAs[J]. Oncotarget, 2016, 7(52): 85709-85727.
[20] Tanwar PS, Kaneko-Tarui T, Zhang L, et al. Constitutive WNT/beta-catenin signaling in murine Sertoli cells disrupts their differentiation and ability to support spermatogenesis[J]. Biol Reprod, 2010, 82(2): 422-432.
[21] Boyer A, Hermo L, Paquet M, et al. Seminiferous tubule degeneration and infertility in mice with sustained activation of WNT/CTNNB1 signaling in sertoli cells[J]. Biol Reprod, 2008, 79(3): 475-485.
[22] Wang XN, Li ZS, Ren Y, et al. The Wilms tumor gene, Wt1, is critical for mouse spermatogenesis via regulation of sertoli cell polarity and is associated with non-obstructive azoospermia in humans[J]. PLoS Genet, 2013, 9(8): e1003645.   
[23]Chang H, Gao F, Guillou F, et al. Wt1 negatively regulates beta-catenin signaling during testis development[J]. Development, 2008, 135(10): 1875-1885.
[24] 张艳萍, 张丽红, 邱毅. 特发性男性不育症患者精子功能检测的临床分析[J]. 生殖与避孕, 2015, 35(7): 489-493.
[25] Yan Q, Wu X, Chen C, et al. Developmental expression and function of DKKL1/Dkkl1 in humans and mice[J]. Reprod Biol Endocrinol, 2012, 10(1): 51.
[26] Ghaffari Novin M, Mirfakhraie R, Nazarian H. Aberrant Wnt/β-catenin signaling pathway in testis of azoospermic men[J]. Adv Pharm Bull, 2015, 5(3): 373-377.
[27] Abdelrazik H, Sharma R, Mahfouz R, et al. L-carnitine decreases DNA damage and improves the in vitro blastocyst development rate in mouse embryos[J]. Fertil Steril, 2009, 91(2): 589-596.
[28] Balercia G, Regoli F, Armeni T, et al. Placebo-controlled double-blind randomized trial on the use of L-carnitine, L-acetylcarnitine, or combined L-carnitine and L-acetylcarnitine in men with idiopathic asthenozoospermia[J]. Fertil Steril, 2005, 84(3): 662-671.
[29]张明明. 麒麟丸联合左卡尼汀治疗特发性少弱精子症临床疗效观察[J]. 生殖与避孕, 2016, 36(4): 332-334.
[30]Majzoub A, Agarwal A. Systematic review of antioxidant types and doses in male infertility: Benefits on semen parameters, advanced sperm function, assisted reproduction and live-birth rate[J]. Arab J Urol, 2018, 16(1): 113-124.
[31] Kim MK, Park JK, Paek SK, et al. Effects and pregnancy outcomes of L-carnitine supplementation in culture media for human embryo development from in vitro fertilization[J]. J Obstet Gynaecol Res, 2018, 44(11): 2059-2066.

基金

云南省科技厅联合专项(2018FE001-015);昆明医科大学研究生创新基金(2019S069)

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