摘要
目的探究淫羊藿苷对自然衰老大鼠睾丸支持细胞(Sertoli细胞)功能减退的改善作用及可能的作用机制。方法将SPF级Sprague-Dawley(SD)雄性大鼠按体重随机分成青年对照组(2月龄)、衰老模型组(17月龄)、淫羊藿苷低和高剂量组(2、6 mg·kg^(-1),17月龄),各组大鼠分别给予普通饲料或含药饲料持续喂养4个月。苏木素-伊红(HE)染色法观察各组大鼠睾丸组织形态学改变。蛋白免疫印迹法(Western blot)检测各组大鼠睾丸组织闭锁小带蛋白1(ZO-1)、闭锁蛋白(occludin)、β-连环蛋白(β-catenin)、早幼粒细胞白血病锌指蛋白(PLZF)、骨形成蛋白4(BMP4)、激活转录因子6(ATF6)和c-fos的蛋白表达和定位。结果HE染色结果发现,淫羊藿苷可明显改善自然衰老大鼠睾丸组织形态学变化。Western blot结果显示,与青年对照组相比,衰老模型组大鼠睾丸组织中ZO-1、occludin、β-catenin、PLZF和BMP4蛋白表达水平均显著下降,而淫羊藿苷可显著上调衰老大鼠睾丸组织中上述蛋白的表达水平。免疫荧光结果显示,与衰老模型组相比,淫羊藿苷能明显上调衰老大鼠睾丸Sertoli细胞中occludin和β-catenin以及通路相关指标ATF6和c-fos蛋白表达水平。结论淫羊藿苷可减轻衰老所致大鼠睾丸Sertoli细胞功能减退,机制可能与激活Sertoli细胞ATF6/c-fos信号通路有关。
OBJECTIVE To investigate the protective effects of icariin on impairment of Sertoli cell function in testis of aging rats and explore the possible mechanism.METHODS Male Sprague-Dawley rats were randomly divided into four groups according to body weight:adult control group(2 months old),aging model group(17 months old),low and high dose of icariin-treated groups(2 and 6 mg·kg^(-1),17 months old).The rats in the adult control group and the aging model group were fed with normal diet for 4 months.Rats in icariin-treated groups were given medicated feed for 4 months.The histological changes of testis were observed by HE staining.In addition,the expression levels of ZO-1,occludin,β-catenin,PLZF,BMP4,ATF6 and c-fos in testis were detected by Western blot.The expression and localization of occludin,β-catenin,ATF6 and c-fos in testis were detected by immunofluorescence.RESULTS HE staining results showed that icariin improved the structure of testicular tissues of natural aging rats.Western blot results showed that the relative protein expression levels of ZO-1,occludin,β-catenin,PLZF and BMP4 in testis were significantly decreased in aging model group when compared with the adult control group.In contrast,icariin increased the relative expression levels of these proteins in the testis of aging rats.Moreover,immunofluorescence results showed that icariin appeared to upregulate the protein expression levels of occludin,β-catenin,ATF6 and c-fos in Sertoli cells of aging rats when compared with the aging model group.CONCLUSION Icariin alleviates the impairment of Sertoli cell function in aging rats and the mechanism may be related to the activation of ATF6/c-fos signaling pathway in Sertoli cells.
作者
朱凯丽
张长城
刘尚雨
赵雪怡
邬小平
袁丁
赵海霞
ZHU Kai-li;ZHANG Chang-cheng;LIU Shang-yu;ZHAO Xue-yi;WU Xiao-ping;YUAN Ding;ZHAO Hai-xia(Third-Grade Pharmacological Laboratory on Traditional Chinese Medicine,State Administration of Traditional Chinese Medicine,China Three Gorges University,Yichang 443002,China;Medical College,China Three Gorges University,Yichang 443002,China)
出处
《中国药学杂志》
CAS
CSCD
北大核心
2022年第23期2004-2012,共9页
Chinese Pharmaceutical Journal
基金
国家自然科学基金项目资助(81873077,82074205)。
