肉桂多酚抑制AGEs/RAGE预防糖尿病大鼠肾损伤的作用  

Prevention of Diabetes-Induced Renal Injury in Rats by Cinnamon Polyphenols via AGEs/RAGE Inhibition

作　　者：黄国栋 尹日凤 覃田田 潘子瑜 周金玲 夏星 HUANG Guodong;YIN Rifeng;QIN Tiantian;PAN Ziyu;ZHOU Jinling;XIA Xing(College of Pharmacy,Guangxi University of Chinese Medicine,Nanning 530200,Guangxi,China;Key Laboratory of Traditional Chinese Medicine Pharmacology of Education Department of Guangxi Zhuang Autonomous Region,Guangxi University of Chinese Medicine,Nanning 530200,Guangxi,China)

机构地区：[1]广西中医药大学药学院,广西南宁530200 [2]广西中医药大学广西高校中药药理重点实验室,广西南宁530200

出　　处：《中华中医药学刊》2023年第8期168-172,I0031,共6页Chinese Archives of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(81960728);广西高校中青年教师科研基础能力提升项目(2022KY0302);广西壮瑶药重点实验室建设项目(GXZYZZ2020-11);广西中医药大学一流学科开放课题项目(2018XK030,2019XK084);广西中医药大学桂派杏林拔尖人才项目(2022C007);广西中医药大学桂派中医药传承创新团队项目(2022B005);广西中医药大学一方制药大学生科技创新项目(2020DXS50)。

摘　　要：目的 研究肉桂多酚(Cinnamon polyphenols, CPS)对长期糖尿病引发肾损伤的保护作用,并探讨其作用机制。方法 利用高脂饲养+腹腔注射链脲佐菌素(Streptozotocin, STZ)的方法引起长期大鼠的糖尿病诱发肾损伤,将大鼠分为模型对照组、厄贝沙坦组、CPS高剂量组(300 mg/kg)、CPS中剂量组(200 mg/kg)及CPS低剂量组(100 mg/kg),连续灌胃治疗8周后,测定各大鼠的空腹血糖(Fasting blood glucose, FBG),尿微量白蛋白(Urine microalbumin, MAU)、尿肌酐(Urine creatinine, Ucr)、血清肌酐(Serum creatinine, Scr)、尿素氮(Blood urea nitrogen, BUN)和血脂水平,测定肾脏系数(Kidney coefficient, KI),并对肾脏进行HE染色观察组织形态;检测糖化血红蛋白(Glycosylated hemoglobin, HbA1c)、糖化血清蛋白(Glycosylated serum protein, GSP)、糖基化终末产物(Advanced glycation end products, AGEs);取肾皮质部用RT-qPCR检测肾脏糖基化终末产物受体(Glycation end products receptor, RAGE),足细胞相关蛋白Nephrin、Podocin mRNA的表达。结果 与模型对照组大鼠相比,CPS各剂量组大鼠的MAU、Ucr、Scr、BUN极显著降低(P<0.01);KI也显著降低(P<0.05);CPS减轻了肾小管上皮细胞空泡变性、颗粒变性、肾小球旁系增生,并显著降低GSP水平及血清AGEs水平;CPS还显著增加了肾脏足细胞相关蛋白Podocin的表达。结论 CPS能显著改善高脂饲养+STZ造成的大鼠肾损伤,其机制可能与减少血清AGEs的积累,并保护足细胞连结有关。Objective To study the protective effect of cinnamon polyphenols(CPS)in diabetes-induced renal injury in rats and discuss the mechanism.Methods The kidney injury in long-term diabetic rats was conducted by high-fat feeding combined with streptozotocin(STZ)injection.Rats were randomized to model control group,irbesartan group,CPS high-dose group(300 mg/kg),medium-dose group(200 mg/kg)and low-dose group(100 mg/kg).After administration by gavage for 8 weeks,the levels of fasting blood glucose(FBG),urine microalbumin(MAU),urine creatinine(Ucr),serum creatinine(Scr),blood urea nitrogen(BUN)and blood lipids were determined.Moreover,the kidneys were collected to determine kidney coefficient(KI)as well as observe the pathological changes by HE staining.Meanwhile,glycosylated hemoglobin(HbA1c),glycosylated serum protein(GSP)and end products of glycation(AGEs)in serum were detected by ELISA and mRNA expressions of glycation end products receptor(RAGE),Podocin and Nephrin in renal cortex were analyzed by RT-qPCR.Results Compared with those of the model group,the levels of MAU,Ucr,Scr,BUN and KI were decreased significantly in CPS each dose group(P<0.01),while KI was obviously decreased(P<0.05).CPS made kidney glomerular vacuolization,granular degeneration and glomerular matrix hyperplasia mitigated and significantly lowered the levels of GSP and AGEs.CPS also significantly increased the expression of Podocin.Conclusion The results showed that CPS can significantly relieve the renal injury in long-term diabetes rats induced by HFT+STZ.The underlying mechanism may be involved in the reduction of serum AGEs and protection of podocytes.

关 键 词：糖尿病肾病 晚期糖基化产物 足细胞 PODOCIN 

分 类 号：R282.71[医药卫生—中药学]