目的 分析中国内脏肥胖指数(CVAI)与健康体检者肾功能下降的关系.方法 选取2020年1月1日至2020年12月31日3221名在丽水市人民医院体检中心(395名)与浙江大学医学院附属第二医院健康管理中心(2826名)进行健康体检的成年人,均按照体检指标计算出CVAI.按照估算的肾小球滤过率(eGFR)水平,将健康体检者分为90 ml/(min·1.73 m2)≤eGFR≤120 ml/(min·1.73 m2)的肾功能正常者2159名和eGFR<90 ml/(min·1.73 m2)的肾功能下降者1062名.比较两者的临床特征和CVAI,并按CVAI四分位分组,采用logistic回归模型分析不同CVAI健康体检者肾功能下降的风险.结果 肾功能下降者CVAI高于肾功能正常者(P<0.05).以Q1组为对照,量化CVAI增加时发生肾功能下降的风险优势比,Q2、Q3、Q4组的OR值(95％CI)分别为2.01(1.51～2.41)、3.11(2.51～4.01)、4.12(3.39～5.26),呈上升趋势(均P<0.05),校正了相关的其他危险因素后趋势仍然一致.结论 CVAI与肾功能下降密切相关,高CVAI者肾功能下降风险较高.CVAI可作为筛查健康体检者肾功能下降的有效指标.

Objective:This study aimed to explore the feasibility and clinical value of monitoring the progression of early kidney injury in type 2 diabetic patients by assessment of the urinary C-terminal agrin fragment (uCAF) with enzymatic chemiluminescence immunoassay.Methods:A total of 251 patients with type 2 diabetes, who attended the Second Affiliated Hospital of Wenzhou Medical University from October 2018 to March 2020, were included in this retrospective analysis. One hundred and fifty-six participants undergoing health check-up at the Second Affiliated Hospital of Zhejiang University School of Medicine in February 2021 served as controls. Basic clinical information, glycosylated hemoglobin type A 1c and serum creatinine values were recorded, and urine specimens were collected for urinary creatinine, urinary α 1 microglobulin(uα 1M), urinary immunoglobulin G (uIgG), urinary albumin, urinary N-Acetyl-B-D-glycosaminidase (uNAG) and uCAF measurements. Based on the estimated glomerular filtration rate (eGFR), 251 patients were classified into G1~G5 stage groups with 116, 22, 28, 55 and 30 patients in each group. One hundred and sixty-six patients with early diabetic kidney disease (stage G1-G3) were divided into subgroups A1 (79), A2 (48) and A3 (39) according to the urinary albumin/creatinine ratio (UACR), the uα1M levels were divided into uα1M subgroup 1 (83 cases), uα1M subgroup 2 (42 cases), and uα1M subgroup 3 (41 cases), and uIgG subgroup 1 (83 cases), uIgG subgroup 2 (42 cases), and uIgG subgroup 3 (41 cases) according to uIgG levels. The Spearman method was used to analyze the correlation between uCAF levels and eGFR, UACR, uα1M and uIgG levels. Results:(1) The linear range of the uCAF detected by enzymatic chemiluminescence immunoassay was 3.97-2 000.00 ng/ml, with a detection limit of 2.28 ng/ml, intra-batch coefficients of variation of 1.15% and 1.57%, inter-batch coefficients of variation of 1.63% and 5.78%, and a biological reference interval of <95.35 μg/g Cr. (2) The uCAF level and positive rate (UACR≥30 mg/g) increased with the decrease of eGFR from G1-G3, uCAF level was negatively correlated with eGFR value ( r=-0.543, P<0.000 1), and the positive rate increased from 24.14% (28/116) to 85.71% (24/28) from G1-G3. The uCAF level and positivity rate decreased with the decrease of eGFR from G4 to G5. uCAF level was positively correlated with eGFR value ( r=0.495, P<0.001), and the positivity rate decreased from 30.91% (17/55) to 23.33% (7/30) from G4 to G5. (3) In patients with early diabetic kidney disease, uCAF levels and positivity rates increased gradually with the increase of UACR. uCAF levels were positively correlated with UACR values ( r=0.602, P<0.001), and the uCAF positivity rate reached 21.52% (17/79) in the A1 subgroup. (4) uCAF level was positively correlated with uα1M and uIgG levels in patients with early diabetic kidney disease ( r=0.757, 0.596, both P<0.001). Conclusion:Analytical performance of enzyme chemiluminescence immunoassay for the detection of CAF is satisfactory and could be used a biomarker for monitoring damage and progression of early diabetic kidney disease in patients with type 2 diabetes.

目的:探讨胰高血糖素样肽1(GLP-1)受体激动剂利拉鲁肽(Lira)早期干预对高脂饮食(HFD)诱导的非酒精性脂肪性肝病(NAFLD)大鼠的影响及沉默信息调节因子1(SIRT1)/AMP活化蛋白激酶(AMPK)通路在其中的作用.方法:SPF级雄性SD大鼠随机分为普通饮食(ND)组、HFD组和HFD+Lira组,每组8只.适应性饲养1周后,按不同分组给药,HFD+Lira组大鼠每日固定时间皮下注射Lira(200μg/kg),其余2组注射等体积生理盐水.干预期间注意观察大鼠体重、毛发、食欲、大小便及活动情况,以便及时调整药量.每周记录体重、进食量和血糖,第16周行葡萄糖耐量实验;第18周末麻醉后行高胰岛素-正葡萄糖钳夹实验,该实验结束后颈动脉取血,处死后取肝脏及不同部位的脂肪组织.血清检测丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)等指标;HE染色法观察肝组织病理损伤变化;油红O染色法观察肝组织脂质蓄积程度;马松染色和天狼星红染色法观察肝脏纤维化程度;活性氧簇(ROS)染色观察肝脏氧化应激情况;免疫荧光染色观察肝脏GLP-1受体表达情况;免疫组织化学染色法观察SIRT1和第172位苏氨酸磷酸化的AMPK[p-AMPK(Thr172)]的表达及定位;Western blot法检测肝组织AMPK、p-AMPK(Thr172)、SIRT1、第372位丝氨酸磷酸化的固醇调节元件结合蛋白1c[p-SREBP-1c(Ser372)]、第79位磷酸化的乙酰辅酶A羧化酶[p-ACC(Ser79)]、肉毒碱棕榈酰转移酶1A(CPT1A)和脂肪酸合成酶(FAS)的蛋白水平.结果:HE和油红O染色结果证实HFD组肝组织结构紊乱,脂质蓄积严重,马松和天狼星红染色显示纤维化程度严重,提示NAFLD大鼠模型建立成功.与ND组相比,HFD组血清总胆固醇(TC)、甘油三酯(TG)、AST和ALT,以及肝组织丙二醛(MDA)、TC、TG和ROS水平均显著升高(P<0.01),超氧化物歧化酶(SOD)活性显著降低(P<0.01),肝组织p-AMPK(Thr172)、SIRT1、p-SREBP-1c(Ser372)、p-ACC(Ser79)和CPT1A蛋白水平显著降低(P<0.05或P<0.01),FAS表达显著增加(P<0.01);与HFD组比较,HFD+Lira组大鼠肝组织脂质蓄积和纤维化程度明显减轻,血清TG、TC、AST和ALT,以及肝组织MDA、TC、TG和ROS水平均显著降低(P<0.05或P<0.01),SOD活性增强(P<0.05),肝组织p-AMPK(Thr172)、SIRT1、p-SREBP-1c(Ser372)、p-ACC(Ser79)和CPT1A蛋白水平显著升高(P<0.05或P<0.01),FAS表达显著减少(P<0.01).结论:Lira能够减轻HFD诱导的NAFLD大鼠胰岛素抵抗、肝纤维化和氧化应激程度,并改善肝脏脂质代谢,其作用可能与SIRT1/AMPK通路有关.