中国中医药科技2026,Vol.33Issue(1):10-15,6.
灵芝多糖通过HIF-1α/BNIP3通路调控自噬对糖尿病肾病小鼠的治疗作用及机制研究
Study on Therapeutic Effect and Mechanism of Ganoderma Lucidum Polysaccharides on Diabetic Nephropathy in Mice Through HIF-1α/BNIP3 Pathway
摘要
Abstract
Objective:To investigate the therapeutic effect of Ganoderma lucidum polysaccharides (GLPs) on mice with diabetic nephropathy (DN) and to elucidate the underlying mechanism. Methods:A mouse model of diabetic nephropathy was established,and C57 mice were randomly divided into five groups:sham-operated group (administered an equal volume of normal saline),model group,HIF-1α agonist group (80 mg/kg),low-dose GLP group (50 mg/kg),and high-dose GLP group (200 mg/kg). Fasting blood glucose (FBG) levels were measured before and at weekly intervals after drug administration. After 28 days,mouse body weight was recorded,and24-hour urinary protein (24 hUP),serum urea nitrogen (BUN),and serum creatinine (SCr) levels were detected using biochemical analysis. Renal histopathological changes were observed via HE and Masson staining. Autophagosomes were examined by transmission electron microscopy (TEM). The expression of autophagy-related proteins in renal tissue was detected by immunofluorescence,and the protein expression levels of HIF-1α,BNIP3,beclin1,LC3,and p62 in renal tissue were measured by Western blot. Results:Compared with the sham-operated group,the model group showed significant weight loss,elevated levels of FBG,24 hUP,BUN,and SCr,marked renal histopathological damage,near disappearance of autophagosomes under TEM,significantly weakened HIF-1α fluorescence intensity in renal tissue,significantly downregulated protein expression levels of HIF-1α,BNIP3,beclin1,and LC3,and a significant upregulation of p62 protein expression(all P<0.05).Compared with the model group,both the GLP treatment groups and the HIF-1α agonist group exhibited significant weight gain,reduced levels of FBG,24 hUP,BUN,and SCr,markedly alleviated renal histopathological damage,significantly increased number of autophagosomes under TEM,enhanced HIF-1α fluorescence intensity in renal tissue,significantly upregulated protein expression levels of HIF-1α,BNIP3,beclin1,and LC3,and a significant downregulation of p62 protein expression(all P<0.05).Conclusion:Ganoderma lucidum polysaccharides exert a significant therapeutic effect on diabetic nephropathy in mice,and the mechanism may be related to the modulation of autophagy through the HIF-1α/BNIP3 pathway.关键词
灵芝多糖/HIF-1α/BNIP3通路/自噬/糖尿病肾病Key words
Ganoderma lucidum polysaccharide/HIF-1α/BNIP3/Autophagy/Diabetic nephropathy引用本文复制引用
陈佳樱..灵芝多糖通过HIF-1α/BNIP3通路调控自噬对糖尿病肾病小鼠的治疗作用及机制研究[J].中国中医药科技,2026,33(1):10-15,6.基金项目
浙江省药学会医院药学专项科研资助项目(2020ZKY08) (2020ZKY08)