黄芪甲苷延缓肾脏衰老的作用及其机制*

doi:10.12047/j.cjap.6300.2022.084

摘要/Abstract

摘要： 目的: 探讨黄芪甲苷是否通过调控SIRT1/p53信号通路而发挥抑制细胞凋亡,延缓大鼠肾脏衰老的作用。方法: SPF级健康雄性SD大鼠,随机分为正常对照组(生理盐水5 ml/(kg·d)灌胃)、衰老模型组(生理盐水5 ml/(kg·d)灌胃)、黄芪甲苷组和SRT1720组(在造模基础上分别施于黄芪甲苷40 mg/(kg·d)和SRT1720 20 mg/(kg·d)灌胃),每组各10只。饲养8周后收集大鼠血清、肾脏组织标本。ELISA法检测血清中肾功能(肌酐、尿素氮)和衰老相关分泌表型(TGF-β、IL-6)的水平;肾脏组织进行HE染色、Masson染色;RT-PCR及Western blot 分别检测SIRT1、p53、Bcl-2、Bax、p21、pRb基因和蛋白水平表达。结果: 衰老模型组大鼠血清肌酐、尿素氮水平较正常组升高,但各组之间比较差异无统计学意义(P＞0.05);衰老模型组大鼠血清中TGF-β、IL-6水平较正常组显著升高(P＜0.05),黄芪甲苷组及SRT1720组大鼠血清TGF-β、IL-6水平较模型组显著下降(P＜0.05),且黄芪甲苷组与SRT1720组比较差异无统计学意义(P＞0.05)。与正常组相比,衰老模型组大鼠的肾小管扩张,局部萎缩,肾间质炎性细胞浸润,胶原纤维增生;黄芪甲苷组及SRT1720组较模型组减轻。与正常组相比,衰老模型组大鼠肾脏组织中SIRT1、pRb蛋白及mRNA表达均显著下降,Bcl-2蛋白表达显著下降(P＜0.05),p53、p21蛋白及mRNA表达显著升高,Bax蛋白表达显著升高(P＜0.05)。与衰老模型组相比,黄芪甲苷组及SRT1720组上述指标的水平均有显著逆转(P＜0.05)。结论: 黄芪甲苷可能通过调控SIRT1/p53信号通路延缓大鼠肾脏衰老。

关键词: 黄芪甲苷, SIRT1/p53信号通路, 肾脏, 衰老, 细胞凋亡

Abstract: Objective: To investigate the mechanisms of Astragaloside Ⅳ on inhibiting apoptosis and delaying kidney aging in rats by regulating SIRT1/p53 signaling pathway. Methods: The aging model was established by subcutaneous injection of D-galactose 200 mg/(kg·d). SPF-grade healthy male SD rats were randomly divided into 4 groups: normal control group (intragastric infusion of 5 ml/(kg·d) normal saline), aging model group (intragastric infusion of 5 ml/(kg·d) normal saline), Astragaloside IV group (intragastric infusion of 40 mg/(kg·d) Astragaloside IV),and SRT1720 group( intragastric infusion of 20 mg/(kg·d) SRT1720), with 10 rats in each group. After 8 weeks, the serum samples of rats were collected to detect the levels of renal function (creatinine and urea nitrogen) and senescent associated secretory phenotype (TGF-β and IL-6) by ELISA. The renal tissues of rats were obtained for HE and Masson staining. The protein and mRNA expressions of SIRT1, p53, Bcl-2, Bax, p21 and pRb were detected by Western blot and RT-PCR. Results: Serum creatinine and urea nitrogen levels in the aging model group were higher than those in the normal group, but there was no significant difference in each group (P＞0.05). The serum levels of TGF-β and IL-6 in the aging model group were higher than those in the normal group (P＜0.05), and which in the Astragaloside IV group and SRT1720 group were lower than those in the model group (P＜0.05). There was no significant differences between Astragaloside IV group and SRT1720 group (P＞0.05). The results of pathological staining of renal tissues showed that, compared with the normal group, the renal tubules dilated, local atrophy, infiltration of inflammatory cells and proliferation of collagen fibers were observed in the aging model group. Compared with the aging model group, the pathological changes were alleviated in Astragaloside IV group and SRT1720 group. The results of Western blot and RT-PCR showed that, compared with the normal group, the protein and mRNA expressions of SIRT1 and pRb in the renal tissue of the aging group were decreased, the protein expression of Bcl-2 was decreased(P＜0.05), and the protein and mRNA expressions of p53 and p21 were increased, the protein expression of Bax was increased(P＜0.05). Compared with the aging group, Astragaloside IV and SRT1720 improved the above-mentioned indexes (P＜0.05). Conclusion: Astragaloside IV can delay kidney aging by regulating the SIRT1/p53 signaling pathway.

Key words: astragaloside IV, SIRT1/p53 signaling pathway, kidney, aging, apoptosis

中图分类号:

R57-2

张紫媛, 方敬爱, 李苏芬, 胡雅玲, 刘文媛, 刘学军. 黄芪甲苷延缓肾脏衰老的作用及其机制^*[J]. 中国应用生理学杂志, 2022, 38(5): 448-452.

ZHANG Zi-yuan, FANG Jing-ai, LI Su-fen, HU Ya-ling, LIU Wen-yuan, LIU Xue-jun. Effects of astragaloside IV on delaying kidney aging and its mechanisms[J]. CJAP, 2022, 38(5): 448-452.

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黄芪甲苷延缓肾脏衰老的作用及其机制^*

Effects of astragaloside IV on delaying kidney aging and its mechanisms

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