司美格鲁肽改善糖尿病肾病模型小鼠肾功能损伤的作用机制  

Mechanism of Semaglutide in Improving Renal Function Damage in Diabetes Nephropathy Model Mice

作　　者：姜啸 姜玫[1] 王智峰[1] 赵涛[1] 曹思明 李秋梅[1] JIANG Xiao;JIANG Mei;WANG Zhifeng;ZHAO Tao;CAO Siming;LI Qiumei(Xinhua Hospital Affiliated to Dalian University,Dalian,Liaoning,China 116021)

机构地区：[1]大连大学附属新华医院,辽宁大连116021

出　　处：《中国药业》2025年第7期45-50,共6页China Pharmaceuticals

基　　金：辽宁省大连市医学科学研究计划项目[2211041]。

摘　　要：目的探讨司美格鲁肽改善糖尿病肾病(DN)模型小鼠肾功能损伤的作用机制。方法随机选取30只SPF级小鼠予高脂饲料(66.5%维持饲料+10%猪油+20%蔗糖+2.5%胆固醇+1%胆酸钠)6周,之后腹腔注射50 mg/kg链脲佐菌素溶液,以复制DN小鼠模型,另选取10只小鼠予常规饲料。将予常规饲料的小鼠设为空白对照组(A组,等量生理盐水),将建模成功的小鼠随机分为模型对照组(B组,等量生理盐水),司美格鲁肽组(C组,60μg/kg),利拉鲁肽组(D组,200μg/kg),各10只,各组小鼠分别腹腔注射相应药物干预8周。检测小鼠的空腹血糖(FBG)、血清肌酐(SCr)和尿素氮(BUN)水平及24 h尿蛋白定量(24 h UTP);采用苏木精-伊红(HE)染色法观察肾组织病理形态变化;采用酶联免疫吸附试验(ELISA)法检测血清白细胞介素(IL)-18、IL-1β表达水平;采用免疫印迹(Western blot)法检测肾组织核因子-κB p65(NF-κB p65)、核苷酸结合结构域富含亮氨酸重复序列和含热蛋白结构域受体3(NLRP3)、胱天蛋白酶-1(caspase-1)蛋白表达水平。结果与B组比较,C组小鼠FBG,血清SCr和BUN水平,24 h UTP,肾脏病理评分,IL-18和IL-1β表达水平,NF-κB p65,NLRP3,caspase-1蛋白表达水平均显著降低(P<0.05),肾组织病理损伤改善。结论司美格鲁肽可显著改善DN模型小鼠的肾功能损伤,其作用机制可能与调控NF-κB/NLRP3信号通路,减轻炎性反应,抑制细胞焦亡有关。Objective To investigate the mechanism of smeglutide in improving renal function damage in diabetes nephropathy(DN)model mice.Methods A total of 30 SPF mice were randomly selected and fed with high-fat diet(66.5%maintenance feed+10%lard+2.5%cholesterol+1%sodium cholate)for six weeks,and then they were intraperitoneally injected with 50 mg/kg streptozotocin solution to replicate the mice model.Another 10 mice were selected and fed with the regular diet.The mice fed with regular diet were set as the blank control group(group A,equal amount of normal saline),and the successfully modeled mice were randomly divided into the model control group(group B,equal amount of normal saline),the semaglutide group(group C,60µg/kg)and liraglutide group(group D,200µg/kg),with 10 mice in each group,and they were intraperitoneally injected with the corresponding drugs for eight weeks.The levels of fasting blood glucose(FBG),serum creatinine(SCr),urea nitrogen(BUN),and the 24 h urinary protein quantification(24 h UTP)in mice were measured.The pathological change of renal tissue was observed by the hematoxylin-eosin(HE)staining method.The expression levels of serum interleukin(IL)-18 and IL-1βwere detected by the enzyme-linked immunosorbent assay(ELISA).The expression of nuclear factor-κB p65(NF-κB p65),NOd-like receptor protein 3(NLRP3)and caspase-1 in renal tissues were detected by the Western blot.Results Compared with those in group B,the levels of FBG,serum SCr,and BUN,the 24 h UTP,renal pathology score,the expression levels of IL-18 and IL-1β,and the expression levels of NF-κB p65,NLRP3,and caspase-1 protein in group C were significantly lower(P<0.05);the renal pathological injury in group C significantly improved(P<0.05).Conclusion Simeglutide can significantly improve renal function injury in DN model mice,and its mechanism may be related to regulating the NF-κB/NLRP3 signaling pathway,reducing inflammatory response,and inhibiting cell apoptosis.

关 键 词：司美格鲁肽 糖尿病肾病 胰高血糖素样肽-1受体激动剂 核因子-κB/核苷酸结合结构域富含亮氨酸重复序列和含热蛋白结构域受体3信号通路 

分 类 号：R965[医药卫生—药理学] R971.2[医药卫生—药学]