【作者】 陈飞；

【导师】 李兵；

【作者基本信息】 吉林大学 ， 临床医学硕士（专业学位）， 2025， 硕士

【摘要】 研究目的:糖尿病肾病(Diabetic nephropathy,DN)已经逐渐成为导致终末期肾脏病的重要原发病,预防及延缓其发生发展至关重要。糖尿病(Diabetes mellitus,DM)微炎症状态被认为与DN的发生及发展密切相关。锌(Zinc,Zn)作为人体必须的微量元素,具有抗炎的作用。TLR4(Toll like receptor-4,TLR4)是调节炎症的重要细胞膜上的受体,其表达受到Zn的调控。我们前期研究证实DN患者存在低Zn血症。因此,本研究旨在探讨在DN患者中,Zn与TLR4表达及全身免疫炎症指数(Systemic immune-inflammation index,SII)的关系,为DN的诊治找到新靶点。研究方法:2022年2月到2024年10月期间于吉林大学第二医院住院患者,其中内分泌科的2型糖尿病(Type 2 diabetes,T2DM)患者31例,肾病内科行肾穿刺活检诊断为DN(不合并其它病理类型)的患者42例。收集上述73例患者的一般资料、实验室资料、DN患者的病理诊断描述进行统计分析、血清样本进行微量元素Zn检测、TLR4及IL-6、TNF-α测定、病理切片进行免疫组化染色。对以上结果进行如下分组:1.73例患者根据有无DN分组:DN组42例,DM组31例。2.73例患者的血清Zn水平按照Zn水平四分位数分为Zn-Q1(≤0.68μg/ml,n=19)、Zn-Q2(0.69μg/ml～0.96μg/ml,n=18)、Zn-Q3(0.97μg/ml～1.13μg/ml,n=18)、Zn-Q4(>1.13μg/ml,n=18)四个组。研究结果:1.DN组血清Zn水平低于DM组,DN组TLR4表达水平、SⅡ高于DM组。血清TLR4(OR:2.388,95%CI:1.482,3.847,P<0.001),SⅡ(OR:1.003,95%CI:1.000,1.006,P<0.05)能独立预测DN。2.Zn-Q1组的估计的肾小球滤过率(estimated glomerular filtration rate,e GFR)、白蛋白显著低于Zn-Q4组(P<0.05),Zn-Q1组血红蛋白显著低于Zn-Q3、Zn-Q4组(P<0.05),Zn-Q1组的TLR4、血肌酐水平显著高于Zn-Q4组(P<0.05),Zn-Q1组尿素氮水平显著高于Zn-Q2、Zn-Q4组(P<0.05)。Zn-Q1、Zn-Q2、Zn-Q3组SⅡ显著高于Zn-Q4组(P<0.05)。3.Zn与TLR4(r=-0.320,P<0.05)、Zn与SⅡ(r=-0.323,P<0.05)呈负相关。TLR4水平与SⅡ呈正相关(r=0.423,P<0.001)。4.血清Zn水平是DN肾间质炎症(OR:0.038,95%CI:0.003,0.525,P<0.05)及间质纤维化及肾小管萎缩(OR:0.08,95%CI:0.008,0.805,P<0.05)的保护因素。研究结论:1.2型DN患者存在低血清Zn、高TLR4表达、高SⅡ。高SⅡ、TLR4是2型DN发病的独立危险因素。2.2型DN中,一定范围内,血清Zn水平越低,SⅡ、TLR4表达水平越高。更多还原

【Abstract】 Purpose:Diabetic nephropathy(DN)has gradually become an important primary cause of end-stage renal disease,and it is crucial to prevent and delay its development.The microinflammatory state of diabetes mellitus(DM)is thought to be closely related to the occurrence and development of DN.Zinc(Zn),an essential trace element,has anti-inflammatory properties,and Zn regulates the expression of Toll like receptor-4(TLR4),an important cell membrane receptor that regulates inflammation.We previously confirmed the presence of hypozincemia in DN patients.Therefore,the aim of this study was to investigate the relationship between Zn and TLR4 expression and systemic immune-inflammation index(SII)in DN patients,and to find new targets for the diagnosis and treatment of DN.Methods:Patients hospitalized at the Second Hospital of Jilin University between February2022 and October 2024.Among them,31 patients with Type 2 diabetes(T2DM)in the Department of Endocrinology,42 patients were diagnosed with DN(not combined with other pathologic types)by renal puncture biopsy performed in the Nephrology department.General data,laboratory data,and DN patients’s description of pathological diagnosis from the above 73 patients were collected for statistical analysis.Serum samples were tested for the trace element Zn,TLR4,IL-6,and TNF-α,and immunohistochemical staining was performed on pathology slides.The results were grouped as follows:1.73 patients were grouped based on their DN status:42 patients in the DN group and 31 patients in the DM group.2.The serum Zn levels of 73 patients were categorized into four groups,Zn-Q1(≤0.68μg/ml,n=19),Zn-Q2(0.69μg/ml～0.96μg/ml,n=18),Zn-Q3(0.97μg/ml～1.13μg/ml,n=18),Zn-Q4(>1.13μg/ml,n=18).Results:1.The serum Zn level was lower in the DN group than the DM group,and TLR4level and SII were higher in the DN group.Serum TLR4(OR:2.388,95%CI:1.482,3.487,P<0.001),SⅡ(OR:1.003,95%CI:1.000,1.006,P<0.05)were independent predictor of the development of type 2 DN.2.Estimated glomerular filtration rate(e GFR)and albumin were lower in the Zn-Q1 group than the Zn-Q4 group(P<0.05).Hemoglobin was lower in the Zn-Q1 group compared to the Zn-Q3 and Zn-Q4 groups(P<0.05).TLR4 and blood creatinine levels were higher in the Zn-Q1 than the Zn-Q4 group(P<0.05).Urea nitrogen levels were higher in the Zn-Q1 group compared to the Zn-Q2 and Zn-Q4 groups(P<0.05).SⅡwas significantly higher in Zn-Q1,Zn-Q2 and Zn-Q3 groups than in Zn-Q4 group(P<0.05).3.Serum Zn was negatively correlated with TLR4(r=-0.32,P<0.05)and SⅡ(r=-0.323,P<0.05).There was a positive correlation between the level of TLR4expression and SII(r=0.423,P<0.001).4.Serum Zn level was a protective factor against renal interstitial inflammation(OR:0.038,95%CI 0.003,0.525,P<0.05)and interstitial fibrosis and tubular atrophy(OR:0.08,95%CI 0.008,0.805,P<0.05)in DN.Conclusions:1.Patients with type 2 DN have low serum zinc,high TLR4 expression,and high SII;High SII and TLR4 are independent risk factors for the development of type2 DN.2.In type 2 DN,within a certain range,the lower the zinc level,the higher the expression level of SII and TLR4.更多还原