肉碱棕榈酰转移酶1α在评估肾纤维化程度和慢性肾脏病进展中的价值  

Value of carnitine palmitoyltransferase 1αexpression for the assessment of the degree of renal fibrosis and the progression of chronic kidney disease

作　　者：袁琦[1,2] 周阳 方奕[1] 丁昊[1] 骆静[1] 徐玲玲[1] 江蕾[1] 杨俊伟[1] Yuan Qi;Zhou Yang;Fang Yi;Ding Hao;Luo Jing;Xu Lingling;Jiang Lei;Yang Junwei(Center for Kidney Disease,the Second Affiliated Hospital of Nanjing Medical University,Nanjing 210003,China;Department of Nephrology,the Affiliated Suzhou Hospital of Nanjing Medical University,Suzhou 215008,China)

机构地区：[1]南京医科大学第二附属医院肾脏病中心,南京210003 [2]南京医科大学附属苏州医院肾内科,苏州215008

出　　处：《中华肾脏病杂志》2021年第1期8-15,共8页Chinese Journal of Nephrology

基　　金：国家自然科学基金[重点项目(81530022),面上项目(81873618)];江苏省社会发展临床前沿技术项目(BE2017762)。

摘　　要：目的探讨慢性肾脏病(chronic kidney disease,CKD)患者肾组织肉碱棕榈酰转移酶1α(carnitine palmitoyltransferase 1α,CPT1α)表达与肾间质纤维化及疾病进展的关系,以及CPT1α在预测肾间质纤维化程度和CKD疾病进展中的价值。方法本研究为回顾性队列研究,纳入2010年3月1日至2017年7月30日间南京医科大学第二附属医院经肾活检证实存在肾小管间质纤维化的CKD患者为研究对象。免疫组织化学法检测肾组织CPT1α蛋白表达,按照CPT1α阳性染色细胞占比的四分位数分为3组:Q1组(阳性染色细胞占比>67.89%)、Q2组(阳性染色细胞占比49.84%~67.89%)和Q3组(阳性染色细胞占比<49.84%)。采用Masson染色评估肾间质纤维化程度;Bodipy脂滴染色评估肾组织脂质沉积程度;实时荧光定量PCR法检测肾组织中CPT1α及胶原等细胞外基质蛋白的mRNA表达量。采用线性回归法分析肾组织CPT1α阳性细胞数占比与肾间质纤维化和肾功能的相关关系;用Pearson相关分析及广义线性模型评估CPT1α阳性细胞数占比与CKD患者肾功能进展的关系;配对比较分析调脂药物对CKD患者肾功能的影响。结果90例CKD患者入选本研究。Masson染色和Bodipy脂滴染色结果显示,与Q1组比较,Q2组和Q3组患者肾间质纤维化和脂质沉积面积增加(均P<0.05)。实时荧光定量PCR结果显示,与Q1组比较,Q2组和Q3组肾组织细胞外基质蛋白的mRNA表达水平增加(均P<0.05)。线性回归分析结果显示,肾间质纤维化面积与CPT1α阳性细胞占比呈负相关(r=-0.309,P<0.01);基线肾组织CPT1α表达阳性细胞占比与血肌酐水平呈负相关(r=-2.801,P<0.001),与eGFR呈正相关(r=1.240,P<0.001)。中位随访时间3.47年,Pearson相关性分析结果显示,CPT1α表达阳性细胞占比与年eGFR变化率相关(r=0.220,P=0.038)。配对分层分析结果显示,Q1组患者用调脂药后无延缓eGFR下降的作用(P>0.05),Q2、Q3组患者用药后可延缓eGFR的下降(均P<0.05)。�Objective To study the relationship between the expression of carnitine palmitoyltransferase 1α(CPT1α)and progression of renal interstitial fibrosis and chronic kidney disease(CKD),and to evaluate the value of CPT1αas a biomarker in pathological diagnosis of renal interstitial fibrosis and CKD.Methods As a retrospective cohort study,information of CKD patients dignosed with tubulointerstitial fibrosis by renal biopsy and receiving follow-up from March 1,2010 to July 30,2017 in the Second Affiliated Hospital of Nanjing Medical University were collected.Renal tissues were stained by immunohistochemistry to detect the expression of CPT1αprotein and then divided into three groups according to the quartile of proportion of CPT1αpositive staining cells,including group Q1(>67.89%),group Q2(49.84%-67.89%)and group Q3(<49.84%).The degree of renal interstitial fibrosis was measured by Masson staining and lipid deposition was represented by Bodipy staining.Messenger RNA of CPT1αand collagen as well as other extracellular matrix genes were detected by real time-PCR.Relationships between proportion of CPT1αpositive staining cells and renal interstitial fibrosis and renal function were analyzed by linear regression analysis.The relationship between CPT1αpositive cell number ratio and renal function progression was measured by Pearson correlation analysis and generalized linear model.The effect of lipid-lowering medicine on renal function of CKD patients was analyzed by paired comparative analysis.Results Ninety patients with CKD were included in this study.Renal interstitial fibrosis and lipid droplets deposition area increased in Q2/Q3 group compared with Q1 group by Masson and Bodipy staining(all P<0.05).Messenger RNA level of extracellular matrix-related proteins increased in Q2/Q3 group by real time-PCR than those of Q1 group(all P<0.05).Linear regression analysis showed that fibrosis area was negatively correlated with the proportion of CPT1αpositive staining cells(r=-0.309,P<0.01).The baseline expression of CPT1

关 键 词：肾 纤维化 肉碱O-软脂酰转移酶 病理学 分子 

分 类 号：R692[医药卫生—泌尿科学]