丹参酮ⅡA对自然衰老大鼠睾丸生殖细胞的损害机制
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摘要
目的探讨丹参酮ⅡA对自然衰老大鼠睾丸生殖细胞的损害机制。方法 SPF级雄性SD大鼠40只。6月龄大鼠10只作为青年对照组,18月龄大鼠作为自然衰老组(n=10)及丹参酮ⅡA低剂量组(n=10)和高剂量组(n=10)。青年对照组和自然衰老组给予生理盐水灌胃,每日1次,连续灌胃6个月;丹参酮ⅡA低剂量和高剂量组分别给予10 mg/kg和30 mg/kg灌胃,每日1次,连续灌胃6个月。比较各组睾丸重量和睾丸指数、睾丸组织形态学、Bcl-2和Bax表达。结果与青年对照组比较,自然衰老组、丹参酮ⅡA低剂量组和高剂量组大鼠睾丸重量降低(P<0.05);与自然衰老组比较,丹参酮ⅡA低剂量组和高剂量组大鼠睾丸重量增加(P<0.05);丹参酮ⅡA高剂量组大鼠睾丸重量高于低剂量组(P<0.05)。与青年对照组比较,自然衰老组、丹参酮ⅡA低剂量组和高剂量组大鼠睾丸指数降低(P<0.05);与自然衰老组比较,丹参酮ⅡA低剂量组和高剂量组大鼠睾丸指数增加(P<0.05);丹参酮ⅡA高剂量组大鼠睾丸指数高于低剂量组(P<0.05)。青年对照组大鼠睾丸组织生精小管界膜完整,并且基膜内能够见排列整齐的各级生精细胞;自然衰老组大鼠睾丸组织生精小管形态结构出现显著变化,生精小管部分增厚,生精细胞层数减少,并且内细胞稀疏,间隙增大;丹参酮ⅡA低剂量和高剂量大鼠睾丸组织相比于自然衰老组,生精小管结构及生精细胞数目显著改善。与青年对照组比较,自然衰老组、丹参酮ⅡA低剂量组和高剂量组大鼠Bcl-2表达降低而Bax表达上升(P<0.05);与自然衰老组比较,丹参酮ⅡA低剂量组和高剂量组大鼠睾丸Bcl-2表达升高而Bax表达下降(P<0.05);丹参酮ⅡA高剂量组大鼠Bcl-2表达高于低剂量组而Bax表达低于低剂量组(P<0.05)。结论丹参酮ⅡA对自然衰老大鼠睾丸生殖细胞损害具有一定保护作用,可抑制衰老造成大鼠睾丸生殖细胞的凋亡,机制可能与上调Bcl-2蛋白和下调Bax蛋白表达相关。
Objective To investigate the protective effect of tanshinone ⅡA on testicular germ cell in naturally aging rats and its possible mechanism. Methods A total of 40 SPF male SD rats were used. Ten 6-month-old rats served as young control group,10 18-month-old rats served as natural aging group,and 10 18-month-old rats served as low and 10 as high doses of tanshinone ⅡA. The young control group and the natural aging group were given saline orally once a day for 6 months. The low and high dose groups of tanshinone ⅡA were given 10 mg/kg and 30 mg/kg,respectively,once a day for 6 months. The testicular weight,testicular index,testicular histomorphology,Bcl-2 and Bax expression levels were compared in each group. Results Compared with the young control group,the testicular weight of rats in the natural aging group,the low dose group and the high dose group decreased(P<0.05);the testicular weight of rats in the low dose group and the high dose group compared with the natural aging group increased(P<0.05);the testicular weight of rats in the high dose group was higher than that in the low dose group(P<0.05). Compared with the young control group,the testicular index of the natural aging group,the low dose group and the high dose group decreased(P<0.05);compared with the natural aging group,the testicular index of the low dose group and the high dose group increased(P<0.05);the testicular index of the high dose group was higher than that of the low dose group(P<0.05). The boundaries of seminiferous tubules in the testicular tissues of young rats in the control group were intact,and spermatogenic cells at all levels could be seen in the basement membrane;the morphology and structure of seminiferous tubules in the testicular tissues of the natural aging group showed significant changes;the seminiferous tubules were partly thicker,the number of spermatogenic cell layers was reduced,and the inner cells were sparse and the gap was increased;compared with the natural aging group,the testis of low-dose and high-dose the structure of seminiferous tubules and the number of spermatogenic cells in the pill tissue were significantly improved. Compared with the young control group,the expression of Bcl-2 decreased and the expression of Bax increased in the natural aging group,the low-dose group and the high-dose group(P<0.05);the low-dose group and the high-dose group compared with the natural aging group the expression of Bcl-2 increased and the expression of Bax decreased(P<0.05);the expression of Bcl-2 in the high-dose group was higher than that in the low-dose group and the expression of Bax was lower than that in the low-dose group(P<0.05). Conclusion Tanshinone ⅡA has a protective effect on testicular germ cell damage in naturally aging rats,and can inhibit the apoptosis of testicular germ cells induced by aging. The mechanism may be related to up-regulation of Bcl-2 protein and down-regulation of Bax protein expression.
Objective To investigate the protective effect of tanshinone ⅡA on testicular germ cell in naturally aging rats and its possible mechanism. Methods A total of 40 SPF male SD rats were used. Ten 6-month-old rats served as young control group,10 18-month-old rats served as natural aging group,and 10 18-month-old rats served as low and 10 as high doses of tanshinone ⅡA. The young control group and the natural aging group were given saline orally once a day for 6 months. The low and high dose groups of tanshinone ⅡA were given 10 mg/kg and 30 mg/kg,respectively,once a day for 6 months. The testicular weight,testicular index,testicular histomorphology,Bcl-2 and Bax expression levels were compared in each group. Results Compared with the young control group,the testicular weight of rats in the natural aging group,the low dose group and the high dose group decreased(P<0.05);the testicular weight of rats in the low dose group and the high dose group compared with the natural aging group increased(P<0.05);the testicular weight of rats in the high dose group was higher than that in the low dose group(P<0.05). Compared with the young control group,the testicular index of the natural aging group,the low dose group and the high dose group decreased(P<0.05);compared with the natural aging group,the testicular index of the low dose group and the high dose group increased(P<0.05);the testicular index of the high dose group was higher than that of the low dose group(P<0.05). The boundaries of seminiferous tubules in the testicular tissues of young rats in the control group were intact,and spermatogenic cells at all levels could be seen in the basement membrane;the morphology and structure of seminiferous tubules in the testicular tissues of the natural aging group showed significant changes;the seminiferous tubules were partly thicker,the number of spermatogenic cell layers was reduced,and the inner cells were sparse and the gap was increased;compared with the natural aging group,the testis of low-dose and high-dose the structure of seminiferous tubules and the number of spermatogenic cells in the pill tissue were significantly improved. Compared with the young control group,the expression of Bcl-2 decreased and the expression of Bax increased in the natural aging group,the low-dose group and the high-dose group(P<0.05);the low-dose group and the high-dose group compared with the natural aging group the expression of Bcl-2 increased and the expression of Bax decreased(P<0.05);the expression of Bcl-2 in the high-dose group was higher than that in the low-dose group and the expression of Bax was lower than that in the low-dose group(P<0.05). Conclusion Tanshinone ⅡA has a protective effect on testicular germ cell damage in naturally aging rats,and can inhibit the apoptosis of testicular germ cells induced by aging. The mechanism may be related to up-regulation of Bcl-2 protein and down-regulation of Bax protein expression.
引文
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[11]王建明,回陈红,刘昊坤,等.何首乌饮对衰老大鼠生精细胞凋亡的影响[J].中国老年学杂志,2017,37(2):266-268.
[12]安福丽,王玉娟,刘昊坤,等.何首乌饮对衰老大鼠生精细胞线粒体凋亡通路关键基因表达的影响[J].解剖学报,2017,48(3):287-295.
[13]任陈,杜莎莎.丹参酮ⅡA在体外对海马神经元细胞放射性损伤的保护作用[J].热带医学杂志,2017,17(5):588-591.
[14]邵炜军,卜艳玲,佟胜举,等.丹参酮ⅡA对缺血再灌注损伤大鼠心肌细胞损伤的保护作用[J].中西医结合心血管病电子杂志,2017,5(20):65-66.
[15]徐颖,梁绍栋,任公平,等.补泻不同配伍补阴方对衰老大鼠抗氧化能力及Bax、Bcl-2、Caspase-3蛋白表达的影响[J].中国老年学杂志,2017,37(20):4974-4976.
[16]马书娟,曹珊,姚建平,等.补肾方对自然衰老大鼠海马CA1区凋亡相关基因Bax、Bcl-2 mRNA表达的影响[J].中药药理与临床,2011,27(3):6-7.2019-01-09
[2]Ding AJ,Zheng SQ,Huang XB,et al.Current perspective in the discovery of anti-aging agents from natural products[J].Nat Prod Bioprospect,2017,7(5):335-404.
[3]李林子,胡文敏,唐靓,等.柠檬苦素对自然衰老大鼠抗氧化和学习记忆能力的影响[J].中国食品卫生杂志,2016,28(1):22-27.
[4]Krut′ko VN,Dontsov VI,Khalyavkin AV,et al.Natural aging as as a sequential poly-systemic syndrome[J].Front Biosci(Landmark Ed),2018,23:909-920.
[5]刘静,赵海霞,吴秋月,等.基于ATR/Chk1/P53信号通路探讨三七总皂苷对自然衰老大鼠睾丸生殖细胞DNA损伤的保护作用[J].中草药,2017,48(5):935-940.
[6]马娜.基于P53/P21和碱基切除修复通路的五子衍宗方对自然衰老大鼠睾丸DNA损伤的保护作用研究[J].中草药,2018,49(6):1379-1384.
[7]何琼笑,赵峻峰.丹参酮ⅡA对缺血再灌注大鼠心肌Notch信号通路的影响[J].中华中医药学刊,2017,12(7):1840-1843.
[8]姚建平,李琳,牛巧能,等.左归丸对自然衰老大鼠海马乙酰胆碱含量及学习记忆功能的影响[J].中成药,2018,40(1):181-183.
[9]马娜,赵海霞,陈茜,等.五子衍宗方对自然衰老大鼠睾丸生殖细胞DNA氧化损伤的保护作用研究[J].中国中药杂志,2018,43(14):18-22.
[10]宋来新,赵海霞,袁丁,等.淫羊藿总黄酮对自然衰老大鼠睾丸细胞凋亡及p-P53、p-P38表达的影响[J].中药材,2016,39(10):2347-2350.
[11]王建明,回陈红,刘昊坤,等.何首乌饮对衰老大鼠生精细胞凋亡的影响[J].中国老年学杂志,2017,37(2):266-268.
[12]安福丽,王玉娟,刘昊坤,等.何首乌饮对衰老大鼠生精细胞线粒体凋亡通路关键基因表达的影响[J].解剖学报,2017,48(3):287-295.
[13]任陈,杜莎莎.丹参酮ⅡA在体外对海马神经元细胞放射性损伤的保护作用[J].热带医学杂志,2017,17(5):588-591.
[14]邵炜军,卜艳玲,佟胜举,等.丹参酮ⅡA对缺血再灌注损伤大鼠心肌细胞损伤的保护作用[J].中西医结合心血管病电子杂志,2017,5(20):65-66.
[15]徐颖,梁绍栋,任公平,等.补泻不同配伍补阴方对衰老大鼠抗氧化能力及Bax、Bcl-2、Caspase-3蛋白表达的影响[J].中国老年学杂志,2017,37(20):4974-4976.
[16]马书娟,曹珊,姚建平,等.补肾方对自然衰老大鼠海马CA1区凋亡相关基因Bax、Bcl-2 mRNA表达的影响[J].中药药理与临床,2011,27(3):6-7.2019-01-09