摘要
目的探讨白藜芦醇(resveratrol,RSV)在氧化三甲胺(trimethylamine N-oxide,TMAO)诱导的快速老化小鼠品系8(senescence-accelerated mouse prone 8,SAMP8)血管衰老中的作用及机制。方法选取36只SPF级24周龄雄性SAMP8小鼠随机分为对照组、TMAO组及TMAO+RSV组(n=12)。对照组正常饮水并灌胃0.5%羧甲基纤维素钠溶液(RSV溶媒),TMAO组给予1.5%TMAO饮水及灌胃等体积溶媒,TMAO+RSV组给予1.5%TMAO饮水及灌胃50 mg/kg RSV。干预16周后,检测小鼠脉搏波传导速度(pulse wave velocity,PWV)、最大主动脉内皮依赖性舒张百分比(maximum endothelium-dependent relaxation,Emax)、主动脉结构、衰老相关β半乳糖苷酶(senescence-associatedβ-galactosidase,SA-β-gal)染色以及P53、P21、沉默信息调节因子2相关酶1(silent mating type information regulation 2 homolog-1,SIRT1)、过氧化物酶体增殖物激活受体γ辅激活因子1α(peroxisome proliferator-activated receptorγcoactivator-1α,PGC-1α)及超氧化物歧化酶2(superoxide dismutase 2,SOD2)蛋白表达。结果与对照组比较,TMAO组小鼠主动脉管腔直径、管壁厚度、管壁面积、弹性纤维断裂数量、SA-β-gal阳性面积、PWV及P53、P2蛋白表达明显升高,Emax、SIRT1、PGC-1α和SOD2表达显著下降(P<0.05)。与TMAO组比较,TMAO+RSV组主动脉管腔直径、管壁厚度、管壁面积以及弹性纤维断裂数量、主动脉P53和P21蛋白表达、PWV明显下降(P<0.05)。与TMAO组比较,TMAO+RSV组小鼠主动脉Emax、SIRT1、PGC-1α和SOD2表达明显升高[(47.43±7.27)%vs(29.48±4.28)%,0.43±0.18 vs 0.18±0.14,0.80±0.26 vs 0.22±0.08,1.22±0.41 vs 0.25±0.07,P<0.05]。结论RSV可改善TMAO加快的SAMP8小鼠血管衰老,其机制可能与激活SIRT1/PGC-1α/SOD2通路有关。
Objective To investigate the role and underlying mechanism of resveratrol(RSV)in trimethylamine N-oxide(TMAO)-induced vascular aging in senescence-accelerated mouse prone 8(SAMP8)mice.Methods A total of 36 male SAMP8 mice(24 weeks old)were randomly divided into control,TMAO,and TMAO+RSV groups,with 12 mice per group.The control group received drinking water and intragastric administration of RSV vehicle,0.5%sodium carboxymethyl cellulose(NaCMC).The TMAO group received drinking water containing 1.5%TMAO and intragastric administration of NaCMC.The TMAO+RSV group received 1.5%TMAO in drinking water and intragastric administration of 50 mg/kg RSV.After 16 weeks of intervention,pulse wave velocity(PWV)and maximum endothelium-dependent relaxation(Emax)were measured,aortic structure and senescence-associatedβ-galactosidase(SA-β-gal)were observed,and the protein expression levels of P53,P21,silent mating type information regulation 2 homolog-1(SIRT1),peroxisome proliferator-activated receptorγcoactivator-1α(PGC-1α),and superoxide dismutase 2(SOD2)were detected.Results Compared with the control group,the TMAO group exhibited significantly larger aortic lumen diameter,thicker wall thickness,increased wall area,more elastic fiber breaks,enhanced SA-β-gal positive area,and higher PWV and protein levels of P53 and P21,whereas obviously decreased Emax and expression levels of SIRT1,PGC-1α,and SOD2(P<0.05).RSV treatment resulted in significant decreases in aortic lumen diameter,wall thickness,wall area,elastic fiber breaks,PWV and protein levels of P53 and P21 in the aorta,and increases in Emax and expression levels of SIRT1,PGC-1αand SOD2[(47.43±7.27)%vs(29.48±4.28)%,0.43±0.18 vs 0.18±0.14,0.80±0.26 vs 0.22±0.08,1.22±0.41 vs 0.25±0.07,P<0.05].Conclusion RSV can ameliorate TMAO-accelerated vascular aging in SAMP8 mice,potentially through activation of the SIRT1/PGC-1α/SOD2 pathway.
作者
柯一郎
周圆圆
潘福祥
李珰
洪华山
KE Yilang;ZHOU Yuanyuan;PAN Fuxiang;LI Dang;HONG Huashan(Department of Geriatrics,Fujian Provincial Institute of Geriatrics,Fujian Provincial Key Laboratory of Vascular Aging,Fujian Provincial Clinical Research Center for Senile Vascular Aging and Brain Aging,Fujian Medical University Union Hospital,Fuzhou 350001,Fujian Province,China)
出处
《中华老年心脑血管病杂志》
北大核心
2026年第3期301-305,共5页
Chinese Journal of Geriatric Heart,Brain and Vessel Diseases
基金
国家自然科学基金(81570448)。
