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番茄红素抑制AGEs/RAGE信号通路对慢性肾功能衰竭大鼠血管钙化的影响

Influence of Lycopene on Vascular Calcification in Rats with Chronic Kidney Failure by Inhibiting AGEs/RAGE Signaling Pathway
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摘要 目的:探究番茄红素(Lyc)抑制糖基化终末产物(AGEs)/AGEs受体(RAGE)信号通路对慢性肾功能衰竭(CKF)大鼠血管钙化的影响。方法:48只大鼠随机分为正常对照组、模型组、阳性对照组(氯沙坦9 mg·kg^(-1))、Lyc低、高剂量组(10和20 mg·kg^(-1))及AGEs激动剂+Lyc高剂量组(AGEs-BSA 40 mg·kg^(-1)+Lyc 20 mg·kg^(-1)),每组8只。除正常对照组外,其余各组采用腺嘌呤喂食法制备大鼠CKF血管钙化模型。采用ELISA试剂盒检测血肌酐(SCr)和血尿素氮(BUN)含量;HE染色观察肾组织病理变化;比色法检测腹主动脉组织中钙含量;Von Kossa染色观察腹主动脉组织钙化情况;比色法检测腹主动脉组织中AGEs含量;Western blot检测腹主动脉组织中RAGE含量。结果:与正常对照组比较,模型组大鼠SCr和BUN含量显著增加(P<0.05);肾组织发生明显病理改变,肾小球内细胞数目增多、结构紊乱,肾小管扩张、坏死,肾皮质变薄、皮髓质界限不清,肾间质可见炎性细胞浸润及纤维化;腹主动脉组织中钙含量显著增加(P<0.05),同时中层可见大量黑色颗粒,发生明显钙化;腹主动脉组织中AGEs和RAGE含量均显著增加(P<0.05)。与模型组比较,Lyc低、高剂量组大鼠SCr和BUN含量均显著减少(P<0.05);肾组织病理损伤减轻;腹主动脉组织中钙含量减少(P<0.05),同时钙化程度减轻;腹主动脉组织中AGEs和RAGE含量均显著减少(P<0.05),高剂量组变化更为显著。与高剂量组比较,AGEs激动剂+高剂量Lyc组大鼠上述情况有所逆转。结论:Lyc能够减轻CKF大鼠肾损伤,改善其血管钙化,可能通过抑制AGEs/RAGE信号通路而实现。 Objective:To investigate the influence of lycopene(Lyc)on vascular calcification in rats with chronic kidney failure(CKF)by inhibiting advanced glycation end products(AGEs)/receptor for AGEs(RAGE)signaling pathway.Methods:Totally 48 rats were randomly divided into normal control group,model group,positive control group(losartan 9 mg·kg^(-1)),Lyc low and high dose groups(10 and 20 mg·kg^(-1)),and ages agonist+Lyc high dose group(AGEs-BSA 40 mg·kg^(-1)+Lyc 20 mg·kg^(-1))with 8 rats in each group.Except the normal control group,CKF vascular calcification model was established by adenine feeding method in the other groups.ELISA was performed to measure serum creatinine(SCr)and blood urea nitrogen(BUN)levels;HE staining was performed to observe the pathological changes of kidney tissue;colorimetric method was performed to measure calcium content in abdominal aorta tissue;Von Kossa staining was used to observe tissue calcification in abdominal aorta;colorimetric method was implemented to measure the content of AGEs in abdominal aorta tissue;Western blot was performed to measure RAGE content in abdominal aorta tissue.Results:Compared with those in the normal control group,the contents of SCr and BUN in the model group were increased(P<0.05);obvious pathological changes occurred in kidney tissue,the number of cells in glomerulus increased,the structure was disordered,renal tubules were dilated and necrotic,renal cortex was thinned,the boundary between cortex and medulla was unclear,and inflammatory cell infiltration and fibrosis were seen in renal interstitium;the calcium content in abdominal aorta tissue increased(P<0.05),and a large number of black particles were seen in the middle layer with obvious calcification;the contents of AGEs and RAGE in abdominal aorta tissue were increased(P<0.05).Compared with those in the model group,the contents of SCr and BUN in Lyc low and high dose groups were decreased(P<0.05);the pathological damage of kidney tissue was alleviated;the calcium content in abdominal aorta tissue was
作者 田莹珺 袁博 梁涛 Tian Yingjun;Yuan Bo;Liang Tao(Department of Laboratory,Second Hospital of Baoding,Hebei Baoding 071051,China;Department of Pediatrics,Affiliated Hospital of Hebei University)
出处 《中国药师》 CAS 2022年第11期1898-1903,共6页 China Pharmacist
关键词 番茄红素 糖基化终末产物/糖基化终末产物受体信号通路 慢性肾功能衰竭 血管钙化 Lycopene Advanced glycation end products/receptor for advanced glycation end products signaling pathway Chronic kidney failure Vascular calcification
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