联苯双酯衍生物对糖尿病肾病和肾功能的影响  

Effect of Bifendate Derivatives on Diabetic Nephropathy and Renal Function

作　　者：柳月娟 李旗 田福玲 高玲焕 赵铭佳[2] Liu Yuejuan;Li Qi;Tian Fuling;Gao Linghuan;Zhao Mingjia(North China University of Science and Technology,Tangshan 063210;Tangshan Maternity and Child Health Care Hospital,Tangshan 063003)

机构地区：[1]华北理工大学,唐山063210 [2]唐山市妇幼保健院,唐山063003

出　　处：《国际老年医学杂志》2024年第4期427-431,共5页International Journal of Geriatrics

基　　金：河北省自然科学基金(H2019209565);河北省中医药管理局科研计划项目(2018175)。

摘　　要：目的 探讨联苯双酯衍生物改善糖尿病肾病及肾功能的相关机制。方法 将50只SPF级6~8周龄C57BL/6J小鼠分为对照组15只和糖尿病肾病模型组35只。对照组再分为正常对照组(7只)以及对照给药组(8只),糖尿病肾病模型组再分为模型组、低剂量给药组、中剂量给药组、高剂量给药组、白藜芦醇阳性药组(各7只)。给药8周后取材。检测小鼠的基本参数和肾功能相关指标,糖原染色实验检测肾组织糖原堆积情况,天狼星红染色检测肾组织纤维化情况,采用Q-Exactive质谱仪进行蛋白质组学分析。分析各比较组间各项指标的差异。结果 不同剂量联苯双酯衍生物均能显著降低小鼠空腹血糖(P<0.05)。中高剂量联苯双酯衍生物能显著降低小鼠血清中尿素氮和肌酐水平(P<0.05)。糖原染色实验提示不同剂量联苯双酯衍生物均能缓解小鼠肾脏糖原堆积。天狼星红染色实验显示不同剂量联苯双酯衍生物均能缓解小鼠肾脏的纤维化病变。蛋白质组学分析共鉴定出5 032种蛋白质,并筛选出104个差异表达蛋白。结论 联苯双酯衍生物有可能成为治疗糖尿病及糖尿病肾病等相关并发症的潜在药物。Objective To explore the mechanism of bifendate derivatives in improving diabetic nephropathy and renal function.Methods Fifty SPF grade 6-8 week old C57BL/6J mice,of which,15 were in the control group and 35 in the diabetic nephropathy model group.The mice in the control group were divided into a normal control group(n=7)and a control administration group(n=8),and the mice in the diabetic nephropathy model group were divided into model group,low-dose administration group,medium-dose administration group,high-dose administration group,and resveratrol-positive drug group(each had 7 mice).Samples were taken after 8 weeks of drug administration.The basic parameters and renal function related indexes of mice were detected,glycogen staining experiments detected the accumulation of glycogen in renal tissues,Sirius red staining detected the fibrosis of renal tissues,and proteomic analysis was performed by Q-Exactive mass spectrometer.The differences of the indexes between the comparison groups were analyzed.Results Different doses of bifendate derivatives significantly reduced fasting blood glucose in mice(P<0.05).Medium and high doses of bifendate derivatives significantly reduced serum urea nitrogen and creatinine levels in mice(P<0.05).Glycogen staining experiments suggested that different doses of benzene bilipid derivatives could alleviate the accumulation of glycogen in the kidneys of mice.Sirius red staining experiments showed that different doses of benzene bisabolol derivatives could alleviate the fibrotic lesions in the kidneys of mice.A total of 5032 proteins were identified by proteomic analysis,and 104 differentially expressed proteins were screened.Conclusion Bifendate derivatives have the potential to be potential drugs for the treatment of diabetes mellitus and related complications such as diabetic nephropathy.

关 键 词：联苯双酯衍生物 糖尿病肾病 肾脏纤维化 差异表达蛋白 

分 类 号：R587.2[医药卫生—内分泌] R692.9[医药卫生—内科学]