黄精提取物改善D-半乳糖所致衰老小鼠器官功能及机制研究  

Effect of Polygonatum sibiricum Extract in Improving the Organ Function of D-Galactose-induced Aging Mice and Its Mechanism

作　　者：解小芬 胡光线 潘露 伍徐娴[2] 周丹 陈九琼 匡梦岚 叶兰 秦臻 许键炜 XIE Xiaofen;HU Guangxian;PAN Lu;WU Xuxian;ZHOU Dan;CHEN Jiuqiong;KUANG Menglan;YE Lan;QIN Zhen;XU Jianwei(School of Basic Medical Science,Guizhou Medical University,Guiyang 550025,China;Guizhou Medical University Tissue Engineering and Stem Cell Experimental Center,National Local Joint Engineering Laboratory of Cell Engineering and Biomedicine Technology,Guizhou Province Key Laboratory of Regenerative Medicine,Guiyang 550025,China;School of Stomatology,Guizhou Medical University,Guiyang 550025,China)

机构地区：[1]贵州医科大学基础医学院,贵州贵阳550025 [2]贵州医科大学组织工程与干细胞实验中心,细胞工程生物医药技术国家地方联合工程实验室,贵州省再生医学重点实验室,贵州贵阳550025 [3]贵州医科大学口腔医学院,贵州贵阳550025

出　　处：《食品工业科技》2023年第18期449-457,共9页Science and Technology of Food Industry

基　　金：中国医学科学院中央级公益性科研院所基本科研业务费专项资金(2018PT31048,2019PT310013);贵州省科学技术基金(黔科合J字[2011]2230号);贵州医科大学博士启动基金(校博合J字[2020]018号)。

摘　　要：目的:旨在探讨黄精提取物(Polygonatum sibiricum extract,PSE)对D-半乳糖(D-galactose,D-gal)致衰老小鼠重要脏器的保护作用及其潜在的分子机制。方法:将小鼠随机分为五组(n=10):对照组、D-gal(500 mg/kg)组、PSE低(0.5 g/kg)、中(1 g/kg)、高(2 g/kg)剂量组。测定小鼠器官指数(胸腺、脾脏、肝脏、肾脏);测定血清中肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、碱性磷酸酶(ALP)、尿酸(UA)、尿素(UREA)、肌酐(CREA)、尿素肌酐比值(BUN/Scr)、肾小球滤过率(eGFR)活性;HE及Masson染色观察各组小鼠皮肤、肝脏、肾脏、心脏、大脑、肺等器官病理学变化;用Real-time PCR法检测各组小鼠肝脏、肾脏、心脏、大脑等组织中p53、p16、p21、RB、HO-1、Nrf2及Keap1 mRNA的表达水平。结果:与D-gal组相比,PSE各剂量组胸腺、脾脏、肝脏和肾脏指数均升高(P<0.05);此外,在各治疗组中,PSE降低了(P<0.05)小鼠血清中CK、CK-MB、ALT、AST、ALP、UA、UREA、CREA和BUN/Scr水平,升高了eGFR(P<0.05)水平;HE及Masson染色发现,PSE能减轻D-gal对小鼠重要器官造成的病理损伤;与对照组比较,模型组肝、肾、心、脑中p53、p16、p21、RB、Keap1 mRNA表达升高(P<0.05),HO-1、Nrf2 mRNA表达降低(P<0.05),与D-gal组比较,PSE各治疗组小鼠肝脏、肾脏、心脏、大脑组织中p53、p16、p21、RB、Keap1 mRNA降低(P<0.05),HO-1、Nrf2 mRNA升高(P<0.05)。结论:PSE具有延缓衰老作用,其机制可能与其抑制p53/p21和p16-RB通路以及Keap1/Nrf2/HO-1通路有关。Objective:The purpose of this study was to explore the protective effects of Polygonatum sibiricum extract(PSE)on the important organs of D-galactose(D-gal)-induced aging mice and its potential molecular mechanisms.Methods:The mice were randomly divided into five groups(n=10):control group,D-gal(500 mg/kg)group,low-PSE dose(0.5 g/kg)group,medium-PSE dose(1 g/kg)group,and high-PSE dose(2 g/kg)group.The organ indices(thymus,spleen,liver,and kidney)were detected.The levels of creatine kinase(CK),creatine kinase isoenzyme(CK-MB),alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP),uric acid(UA),urea(UREA),creatinine(CREA),urea–creatinine ratio(BUN/Scr),and glomerular filtration rate(eGFR)in serum were measured.Pathological changes in the skin,liver,kidney,heart,brain,and lung of mice in different groups were analyzed by HE and Masson staining.The expressions of p53,p16,p21,RB,HO-1,Nrf2,and Keap1 mRNA in the liver,kidney,heart,and brain of each group of mice were detected by real-time PCR.Results:The thymus,spleen,liver,and kidney indices were increased in each PSE treatment group compared with those in the D-gal group(P<0.05).Moreover,in each treatment group,PSE decreased(P<0.05)the levels of CK,CK-MB,ALT,AST,ALP,UA,UREA,CREA,and BUN/Scr in mouse serum and increased the level of eGFR(P<0.05).HE and Masson staining showed that PSE could reduce the pathological damage caused by D-gal to the vital organs of mice.Compared with the blank group,the model group presented increased expression levels of p53,p16,p21,RB,and Keap1 mRNA in the liver,kidney,heart,and brain(P<0.05)and decreased HO-1 and Nrf2 mRNA(P<0.05).Compared with the D-gal group,mice in each PSE treatment group exhibited decreased mRNA levels of p53,p16,p21,RB,and Keap1 in the liver,kidney,heart,and brain tissues(P<0.05)and increased mRNA levels of HO-1 and Nrf2(P<0.05).Conclusion:PSE has anti-aging effects,and its mechanism may be related to its inhibition of the p53/p21,p16-RB,and Keap1/Nrf2/HO-1 pathways.

关 键 词：黄精提取物 抗衰老 p53/p21 信号通路 p16-RB 信号通路 Keap1/Nrf2/HO-1 信号通路 

分 类 号：TS201.4[轻工技术与工程—食品科学]