灵芝多糖肽对糖尿病肾病小鼠氧化损伤的保护作用及机制  

Protective effect and mechanism of ganoderma lucidum polysaccharide peptide on oxidative damage in diabetic nephropathy mice

作　　者：蒋丹容 林冬梅 王联福 游育红[3] JIANG Dan-rong;LIN Dong-mei;WANG Lian-fu;YOU Yu-hong(Pharmacy Department,Nanping First Hospital Affiliated to Fujian Medical University,Nanping 353000,Fujian Province,China;National Fungus Engineering Technology Research Center,Fuzhou 350004,Fujian Province,China;Department of Pharmacy,School of Pharmacy,Fujian Medical University,Fuzhou 350004,Fujian Province,China)

机构地区：[1]福建医科大学附属南平第一医院药剂科,福建南平353000 [2]国家菌草工程技术研究中心,福建福州350004 [3]福建医科大学药学院药理系,福建福州350004

出　　处：《中国临床药理学杂志》2024年第13期1918-1922,共5页The Chinese Journal of Clinical Pharmacology

基　　金：福建省自然科学基金资助项目(2020J011315)。

摘　　要：目的探讨灵芝多糖肽(GLPP)对糖尿病肾病小鼠肾功能及氧化损伤的影响及其作用机制。方法将C57小鼠随机分为正常组、模型组、阳性对照组(10.0 mg·kg^(-1)氯沙坦)、低剂量实验组(50 mg·kg^(-1)GLPP)、中剂量实验组(100 mg·kg^(-1)GLPP)、高剂量实验组(200 mg·kg^(-1)GLPP)、GLPP+Losartan组(200 mg·kg^(-1)GLPP+10.0 mg·kg^(-1)氯沙坦),每组10只小鼠,各组小鼠连续灌胃8周。检测各组小鼠血糖,用生化分析仪检测血清肾功能及脂代谢相关指标,用酶联免疫吸附试验(ELISA)法检测血清炎性因子表达,用蛋白质印迹法检测蛋白相对表达水平,用试剂盒法检测氧化损伤相关指标,用Tunel法检测细胞凋亡。结果正常组、模型组、阳性对照组、高剂量实验组、GLPP+Losartan组小鼠空腹血糖分别为(4.69±0.16)、(20.31±2.04)、(10.22±0.98)、(10.26±0.96)和(7.76±0.43)mmol·L^(-1),血清肌酸酐(Scr)水平分别为(25.48±2.33)、(68.34±4.78)、(32.93±3.25)、(36.37±2.36)和(28.30±1.19)μmol·L^(-1),丙二醛(MDA)含量分别为(2.05±0.22)、(6.71±0.57)、(2.69±0.27)、(3.21±0.32)和(2.19±0.11)nmol·L^(-1),Tunel阳性细胞率分别为(3.39±0.27)%、(26.75±1.24)%、(6.81±0.71)%、(8.05±0.80)%和(5.33±0.33)%,核因子κB(NF-κB p65)蛋白相对表达水平分别为0.31±0.05、1.07±0.08、0.40±0.03、0.47±0.04和0.35±0.03。模型组上述指标与正常组比较,高剂量实验组上述指标与模型组比较,GLPP+Losartan组上述指标与高剂量实验组比较,在统计学上差异均有统计学意义(均P<0.05)。结论灵芝多糖肽可能调节Toll样受体4/NF-κB通路抑制细胞凋亡和炎性反应,改善糖尿病肾病小鼠氧化损伤。Objective To investigate the effects of ganoderma lucidum polysaccharide peptide(GLPP)on renal function and oxidative damage in diabetic nephropathy mice and its mechanism.Methods C57 mice were randomly divided into normal group,model group,positive control group(10.0 mg·kg^(-1)losartan),experimental-L group(50 mg·kg^(-1)GLPP),experimental-M group(100 mg·kg^(-1)GLPP),experimental-H group(200 mg·kg^(-1)GLPP)and GLPP+Losartan group(200 mg·kg^(-1)GLPP+10.0 mg·kg^(-1)losartan).Each group had10 mice.After 8 weeks of continuous gastric administration,blood glucose was detected;renal function and lipid metabolism related indexes were detected by biochemical analyzer;serum inflammatory factor expression was detected by enzyme linked immunosorbent assay(ELISA);protein expression was detected by Western blot;oxidative damage related indexes were detected by kit method;apoptosis was detected by Tunel method.Results The fasting blood glucose of mice in normal group,model group,positive control group,experimental-H group and GLPP+Losartan group were(4.69±0.16),(20.31±2.04),(10.22±0.98),(10.26±0.96)and(7.76±0.43)mmol·L^(-1);serum creatinine(Scr)level were(25.48±2.33),(68.34±4.78),(32.93±3.25),(36.37±2.36)and(28.30±1.19)μmol·L^(-1),respectively;malonaldehyde(MDA)content were(2.05±0.22),(6.71±0.57),(2.69±0.27),(3.21±0.32)and(2.19±0.11)nmol·L^(-1),respectively;Tunel positive cell rates were(3.39±0.27)%,(26.75±1.24)%,(6.81±0.71)%,(8.05±0.80)%,(5.33±0.33)%,respectively;nuclear factor kappa B(NF-κB p65)protein expression levels were 0.31±0.05,1.07±0.08,0.40±0.03,0.47±0.04 and 0.35±0.03,respectively.The model group compared with the normal group for the above indicators,the experimental-H group compared with the model group for the above indicators,and the GLPP+Losartan group was compared with the experimental-H group for the above indicators,all differences were statistically significant in statistics(all P<0.05).Conclusion Ganoderma lucidum polysaccharide peptide may regulate Toll-like receptor 4

关 键 词：灵芝多糖肽 糖尿病肾病 小鼠 氧化损伤 细胞凋亡 Toll样受体4/核因子κB通路 

分 类 号：R28[医药卫生—中药学]