Tirzepatide通过抑制氧化应激和炎症改善糖尿病肾损伤  

Tirzepatide Improves Diabetic Kidney Injury by Inhibiting Oxidative Stress and Inflammation

作　　者：赵江雁 张雨晴 雷敏 陈清杰[2] 郭西英 ZHAO Jiang-yan;ZHANG Yu-qing;GUO Xi-ying(School of Pharmacy,Xianning Medical College,Hubei University of Science and Technology,Xianning Hubei 437100,China)

机构地区：[1]湖北科技学院医学部药学院,湖北咸宁437100 [2]湖北科技学院医学部医药研究院糖尿病心脑血管病变湖北省重点实验室

出　　处：《湖北科技学院学报（医学版）》2024年第3期193-197,共5页Journal of Hubei University of Science and Technology(Medical Sciences)

基　　金：国家自然科学基金(82270892);湖北科技学院博士启动基金(BK202027)。

摘　　要：目的探讨Tirzepatide对糖尿病(DM)SD大鼠肾损伤的改善作用。方法高脂喂养联合STZ腹腔注射构建大鼠DM模型,治疗组大鼠灌胃给予Tirzepatide。ELISA检测大鼠肾组织中SOD活化和MDA含量;HE和PAS染色检测肾脏结构变化和糖原沉积;qRT-PCR检测IL-6、IL-1β、TNF-α的基因表达;Western blot法检测PKC-α、p-NF-κB/NF-κB、iNOS蛋白的表达。结果与DM组相比,Tirzepatide治疗组大鼠肾脏组织中SOD显著上调,MDA含量显著下调(P<0.05);尿白蛋白和尿肌酐排泄减少,肾脏结构改善。Tirzepatide治疗组PKC-α、p-NF-κB/NF-κB、iNOS蛋白表达水平均下调,IL-6、IL-1β、TNF-α基因表达均下调,显示炎症通路被抑制。结论Tirzepatide可能通过抑制氧化应激和炎症通路缓解DM大鼠肾脏组织的氧化损伤。Objective To investigate the effects of Tirzepatide on oxidative stress and inflammatory response in the kidney of diabetic SD rats.Methods The rats model of DM was established by high fat feeding combined with STZ intraperitoneal injection(STZ,35 mg/kg),and the treatment group was given Tirzepatide.SOD activation and MDA content in rat kidney tissue were detected by ELISA.Renal structural changes and glycogen deposition were detected by HE and PAS staining.The expression of IL-6,IL-1β,TNF-αgene was detected by qRT-PCR.The expression of PKC-α,p-NF-κB/NF-κB and iNOS protein was detected by Western blot.Results Compared with DM group,SOD in kidney tissue of Tirzepatide group was significantly up-regulated and MDA content was significantly down-regulated.urinary albumin and urinary creatinine excretion decreased and renal structure improved.In Tirzepatide group,the expression levels of PKC-α,p-NF-κB/NF-κB and iNOS protein were down-regulated,and the expressions of IL-6,IL-1βand TNF-αgenes were down-regulated,indicating that the inflammatory pathway was inhibited.Conclusion Tirzepatide may alleviate oxidative damage in renal tissue of DM rats by inhibiting oxidative stress and inflammatory pathways.

关 键 词：Tirzepatide 糖尿病 肾损伤 氧化应激 炎症 

分 类 号：R965[医药卫生—药理学]