摘要
目的:从抑制肾脏核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)的角度,研究肉桂多酚(CPS)减轻糖尿病大鼠肾脏损伤的作用机制。方法:以高脂饲料联合腹腔注射链脲佐菌素诱发大鼠糖尿病,对成模动物分别以厄贝沙坦(27 mg/kg)、CPS高剂量、中剂量、低剂量(200、100、50 mg/kg),连续给药8周,给药后检测大鼠空腹血糖(FBG)、总胆固醇(TC)、三酰甘油(TG)、尿微量白蛋白(MAU)、糖化血清蛋白(GSP)及肾脏指数(KI)水平;过典酸雪夫氏(PAS)染色、过碘酸六胺银(PASM)染色观察肾组织病理变化;酶联免疫吸附试验法检测血清白细胞介素-1β(IL-1β)水平;蛋白质印迹法检测NLRP3、胱天蛋白酶-1(Caspase-1)、IL-1β相关蛋白表达水平。结果:与正常组比较,模型组大鼠FBG、GSP、KI、MAU、血清IL-1β含量、肾脏NLRP3、Caspase-1、IL-1β蛋白表达升高(P<0.01、P<0.05),肾脏病理损伤加重。CPS能降低糖尿病大鼠的FBG(P<0.01)、KI(P<0.05)、MAU、TC、TG(P<0.01)、GSP(P<0.05)含量;血清IL-1β含量、肾皮质NLRP3、Caspase-1、IL-1β蛋白表达(P<0.05)水平下调;肾小管上皮细胞病理损伤得到改善。结论:CPS抑制大鼠肾脏内NLRP3活化及NLRP3介导的IL-1β成熟,减轻糖尿病大鼠肾组织的炎症反应,对糖尿病肾病大鼠肾脏损伤起到保护作用。
Objective:To investigate the protective mechanism of cinnamon polyphenols(CPS) against kidney injury in diabetic rats,with a focus on the inhibition of renal NOD-like receptor family pyrin domain-containing 3(NLRP3).Methods:A diabetic rat model was established via a high-fat diet combined with intraperitoneal injection of streptozotocin(STZ).Diabetic rats were treated with irbesartan(27 mg/kg),and high-,medium-,and low-dose CPS(200,100,and 50 mg/kg),with continuous administration for 8 weeks.After treatment,fasting blood glucose(FBG),total cholesterol(TC),triglycerides(TG),microalbuminuria(MAU),glycated serum protein(GSP),and kidney index(KI) were measured.Renal histopathological changes were assessed by periodic acid-Schiff(PAS) and periodic acid-silver methenamine(PASM) staining.Serum interleukin-1β(IL-1β) levels were detected by enzyme-linked immunosorbent assay(ELISA),and the protein expression of NLRP3,caspase-1,and IL-1β was analyzed by Western blot.Results:Compared with the normal group,the model group exhibited significantly increased levels of FBG,GSP,KI,MAU,serum IL-1β,and renal NLRP3,caspase-1,and IL-1β protein expression(P<0.01 or P<0.05),accompanied by aggravated renal pathological damage.CPS treatment significantly reduced FBG(P<0.01),KI(P<0.05),MAU,TC,TG(P<0.01),and GSP(P<0.05) levels.Additionally,CPS downregulated serum IL-1β and renal cortical expression of NLRP3,caspase-1,and IL-1β protein expression(P<0.05),and alleviated tubular epithelial cell injury.Conclusion:CPS alleviates renal inflammation in diabetic rats by inhibiting NLRP3 activation and NLRP3-mediated IL-1β maturation,thereby exerting a protective effect against diabetic nephropathy.
作者
黄凤
覃田田
黄国栋
周金玲
夏星
HUANG Feng;QIN Tiantian;HUANG Guodong;ZHOU Jinling;XIA Xing(College of Pharmacy,Guangxi University of Chinese Medicine,Nanning 530200,China;Key Laboratory of Neuro-metabolism and Immunopharmacology of Guangxi Education Department,Guangxi University of Chinese Medicine,Nanning 530200,China)
出处
《世界中医药》
北大核心
2025年第6期932-937,共6页
World Chinese Medicine
基金
国家自然科学基金项目(81960728)
2022年广西高校中青年教师科研基础能力提升项目(2022KY0302)
2021年广西中医药大学博士科研启动基金项目(2021BS007)
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)
广西中医药大学岐黄工程高层次人才团队培育项目(202405)
广西高水平中医药重点学科“中药药理学”建设项目(桂中医药科教发[2023]13号)。
关键词
肉桂多酚
糖尿病
肾损伤
炎症反应
炎症小体
白细胞介素-1Β
链脲佐菌素
中医药治疗
Cinnamon polyphenols
Diabetes mellitus
Kidney injury
Inflammatory responses
Inflammasome
Interleukin-1β
Streptozotocin
Chinese medical therapy
