摘要
目的探究胡黄连苷Ⅱ(PⅡ)调节脂肪酸合成酶(Fas)/脂肪酸合成酶配体(FasL)信号通路对糖尿病肾病(DN)大鼠的治疗作用。方法用高糖高脂喂养联合注射链脲佐菌素(STZ)方法构建DN大鼠模型。将DN大鼠分为模型组(DN组)、PⅡ低、中、高剂量组(P-L组、P-M组、P-H组)、P II高剂量组+Fas重组蛋白组(P-H+rh-Fas组),另选健康大鼠作Control组,每组18只。检测大鼠空腹血糖(FBG)、体质量、24 h尿蛋白(24 h UTP)、肾功能(SCr、BUN);用HE染色和Masson染色观察各组大鼠肾组织病理变化;Western blot检测RAGE、COL-Ⅳ和通路蛋白表达。结果与Control组比较,DN组大鼠肾小球基底膜增厚,系膜增生,肾小管变性、扩张、萎缩,有脂肪变性,大量胶原沉积,FBG、24 h UTP、SCr、BUN、TNF-α、IL-6、IL-1β水平上升,体质量下降,RAGE、COL-Ⅳ、Fas、FasL表达升高(P<0.05);与DN组比较,P-L、P-M、P-H组肾小球、肾小管病变减轻,胶原沉积减少,FBG、24 h UTP、SCr、BUN、TNF-α、IL-6、IL-1β水平降低,体质量上升,RAGE、COL-Ⅳ、Fas、FasL表达下降(P<0.05);与P-H组相比,P-H+rh-Fas组肾组织病变加重,FBG、24 h UTP、SCr、BUN、TNF-α、IL-6、IL-1β水平升高,体质量降低,RAGE、COL-Ⅳ、Fas、Fas L表达上升(P<0.05)。结论胡黄连苷Ⅱ通过抑制Fas/Fas L信号通路发挥对DN大鼠的治疗作用。
Objective To explore the therapeutic effect of picroside II(P II)on diabetes nephropathy(DN)rats by regulating fatty acid synthase(Fas)/fatty acid synthase ligand(FasL)signaling pathway.Methods A DN rat model was constructed by combining high sugar and high-fat diet with streptozotocin(STZ)injection.DN rats were grouped into model group(DN group),low,medium and high dose picroside II groups(P-L group,P-M group,P-H group),and high dose picroside II+Fas recombinant protein group(P-H+rh-Fas group),with healthy rats as control group,and 18 rats in each group.Fasting blood glucose(FBG),body mass,24-hour urinary protein(24h UTP),and renal function(SCr,BUN)were measured in rats.Hematoxylin-eosin(HE)staining and Masson staining were applied to observe the pathological changes in renal tissue of rats;immunohistochemistry and Western blot were applied to detect the expression of RAGE,COL-IV and pathway proteins,respectively.Results Compared with the control group,rats in DN group showed thickening of the glomerular basement membrane,mesangial proliferation,tubular degeneration,dilation,atrophy,fatty degeneration,obvious collagen deposition,higher levels of FBG,24h UTP,SCr,BUN,TNF-α,IL-6 and IL-1β,body mass loss,and higher expression of RAGE,COL-IV,Fas and FasL(P<0.05).Compared with the DN group,the glomerular and tubular lesions were reduced and collagen deposition was decreased in the P-L,P-M and P-H groups,furthermore,the FBG,24h UTP,SCr,BUN,TNF-α,IL-6,IL-1βlevels were lower,body mass was higher,and the RAGE,COL-IV,Fas,FasL expression was lower(P<0.05).Compared with the P-H group,the renal tissue lesions in the P-H+rh-Fas group worsened,the FBG,24 h UTP,SCr,BUN,TNF-α,IL-6,IL-1βlevels were higher,body mass was lower,and the RAGE,COL-IV,Fas,FasL expression was higher(P<0.05).Conclusion Picroside II exerts therapeutic effects on DN rats by inhibiting the Fas/FasL signaling pathway.
作者
董钊
侯健
武士芳
刘颜
郭智慧
刘雪楠
郑超
张卫欢
DONG Zhao;HOU Jian;WU Shifang;LIU Yan;GUO Zhihu;LIU Xuenan;ZHENG Chao;ZHANG Weihuan(Second Department of Endocrinology,Kailuan General Hospital,Tangshan 063000,China;Department of Clinical Laboratory,Kailuan General Hospital,Tangshan 063000,China;Department of Pediatric Respiratory and Critical Care Medicine,Tangshan Maternal and Child Health Hospital,Tangshan 063000,China;Department of Emergency,Kailuan General Hospital,Tangshan 063000,China;Human Resources,Kailuan General Hospital,Tangshan 063000,China)
出处
《免疫学杂志》
2025年第4期217-223,共7页
Immunological Journal
基金
河北省医学研究课题(20242347)。
