川陈皮素对糖尿病肾脏损伤大鼠血小板活化因子的调节作用  

Regulatory effect of nobiletin on platelet-activating factor in diabetic rats with renal injury

作　　者：仝森 罗世翠 杨秋琼 宋波 杨榆青 武俊紫 TONG Sen;LUO Shi-cui;YANG Qiu-qiong;SONG Bo;YANG Yu-qing;WU Jun-zi(School of Basic Medical Sciences,Yunnan University of Chinese Medicine;Yunnan Key Laboratory of Integrated Traditional Chinese and Western Medicine for Chronic Disease in Prevention and Treatment,Kunming 650500,China)

机构地区：[1]云南中医药大学基础医学院 [2]云南省中西医结合慢病防治重点实验室,昆明650500

出　　处：《解剖学报》2024年第5期595-603,共9页Acta Anatomica Sinica

基　　金：云南省科技厅中医联合专项(202101AZ070001-046)。

摘　　要：目的探讨川陈皮素对糖尿病肾脏损伤大鼠血小板活化因子(PAF)代谢的影响。方法72只大鼠随机分为正常组10只和模型制造组62只。模型制造组大鼠构建糖尿病肾脏损伤模型后,再分为模型组、阿司匹林组(20 mg/kg)、川陈皮素低、中、高剂量组(50、100、200 mg/kg),每组10只。连续灌胃6周后检测大鼠体重、肾重、肾指数;HE、过碘酸-希夫染色(PAS)、Masson染色及透射电子显微术观察肾脏病理学形态;检测大鼠血糖、肾功能、炎性因子、PAF及其调控因子;Western blotting和免疫组织化学法检测肾组织中PAF代谢相关蛋白[PAF乙酰水解酶(PAFAH)、PAF受体(PAFR)、胆碱磷酸转移酶1(CHPT1)]的表达水平。结果川陈皮素干预后,大鼠体重增加,肾重及肾指数减轻;肾组织病理学形态改善,间质纤维化程度减轻,基底膜厚度变薄;空腹血糖和糖化血红蛋白降低,空腹胰岛素无明显改善;尿素氮、血肌酐、胱抑素C及24 h尿蛋白排泄量减少;白细胞介素(IL)-1α、IL-6、IL-8、肿瘤坏死因子α(TNF-α)降低;PAF及其调控因子减少;PAFR和CHPT1表达降低,PAFAH升高。结论川陈皮素能够减轻糖尿病肾脏损伤大鼠肾脏损伤状态,改善肾功能,调节血糖,减轻炎症反应,其机制可能与调节血小板活化因子代谢有关。Objective To investigate the effect of nobiletin on platelet-activating factor(PAF)metabolism in diabetic rats with renal injury.Methods Totally 72 rats were randomly divided into control group(n=10)and modeling group(n=62).The modeling group rats were induced to develop a diabetic rat model with renal injury and then further divided into the model group,aspirin group(20 mg/kg),and nobiletin low(50 mg/kg),medium(100 mg/kg),and highdose(200 mg/kg)groups,each with 10 rats.After continuous oral administration for 6 weeks,rat body weight,kidney weight,and kidney index were measured.Histopathological assessments were conducted by using HE,periodic acid-Schiff staining(PAS),Masson staining,and transmission electron microscopy.Blood glucose levels,renal function,inflammatory factors,PAF and its regulatory factors were detected.Expression levels of PAF metabolism-related proteins PAF-acetylhydrolase(PAFAH),PAF receptor(PAFR),and cholinephosphotransferase 1(CHPT1)in kidney tissues were assessed using Western blotting and immunohistochemistry.Results Following nobiletin intervention,rat body weight increased while kidney weight and kidney index decreased.Improvement in renal tissue pathology was observed,with reduced interstitial fibrosis and thinner basement membrane.Fasting blood glucose and glycated hemoglobin decreased,while fasting insulin showed no significant improvement.Urea nitrogen,blood creatinine,cystatin C,and 24-hour urinary protein excretion were reduced.Levels of interleukin(IL)-lα,IL-6,IL-8,and tumor necrosis factor(TNF-α)were lowered.PAF and its regulatory factors decreased.PAFR and CHPT1 expression decreased,while PAFAH increased.ConclusionNobiletin can alleviate renal injury in diabetic rats with renal injury,improve kidney function,regulate blood glucose,and mitigate inflammatory response.Its mechanism may be associated with the modulation of platelet-activating factormetabolism.

关 键 词：糖尿病肾脏损伤 川陈皮素 血小板活化因子 免疫印迹法 免疫组织化学 大鼠 

分 类 号：R285.5[医药卫生—中药学]