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OA
Study on Therapeutic Effect and Mechanism of Ganoderma Lucidum Polysaccharides on Diabetic Nephropathy in Mice Through HIF-1α/BNIP3 Pathway
目的:探究灵芝多糖通过HIF-1α/BNIP3 通路调控自噬对糖尿病肾病小鼠的治疗作用及其作用机制.方法:构建糖尿病肾病小鼠模型,将C57 小鼠随机分为5 组,分别为假手术组、模型组、HIF-1α激动剂组(80 mg/kg)、灵芝多糖低剂量组(50 mg/kg)、灵芝多糖高剂量组(200 mg/kg).给药前和给药后间隔1 周分别检测各组小鼠空腹血糖(FBG);28 d后,称量小鼠体质量;采用生化分析法检测 24 h尿蛋白量(24 hUP)和血清尿素氮(BUN)、肌酐(SCr)含量;HE和Masson染色法观察肾组织病理变化;透射电镜观察自噬体;免疫荧光法检测肾组织内相关蛋白表达;Western blot 法检测肾组织内HIF-1α、BNIP3、beclin1、LC3、p62 蛋白表达.结果:与假手术组相比,模型组小鼠体质量显著减轻,FBG、24 hUP、BUN、SCr水平均显著升高,肾组织病理损伤明显,透射电镜下自噬体基本消失,肾组织内HIF-1α荧光强度显著减弱,HIF-1α、BNIP3、beclin1、LC3 蛋白表达水平显著下调(P<0.05),p629 蛋白表达水平显著上调(P<0.05);与模型组相比,灵芝多糖治疗组和HIF-1α激动剂组小鼠体质量显著增加,FBG、24 hUP、BUN、SCr水平均显著降低,肾组织病理损伤明显被抑制,透射电镜下自噬体数量显著增多,肾组织内HIF-1α荧光强度显著增强,HIF-1α、BNIP3、beclin1、LC3 蛋白水平显著上调(P<0.05),p62 蛋白水平显著下调(P<0.05).结论:灵芝多糖对糖尿病肾病小鼠具有明显的治疗作用,其机制可能与HIF-1α/BNIP3 通路调控自噬有关.
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.
陈佳樱
武警浙江省总队医院·浙江 杭州 310051
灵芝多糖HIF-1α/BNIP3通路自噬糖尿病肾病
Ganoderma lucidum polysaccharideHIF-1α/BNIP3AutophagyDiabetic nephropathy
《中国中医药科技》 2026 (1)
10-15,6
浙江省药学会医院药学专项科研资助项目(2020ZKY08)
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