糖尿病肾病患者脂肪酸结合蛋白水平的改变与临床
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摘要
研究目的：
本研究旨在测定老年糖尿病患者中血清脂肪酸结合蛋白(FABP)水平,分析糖尿病肾病患者FABP的变化及其他相关指标间的关系。探讨其对糖尿病肾病的预测的价值。
材料和方法：
选取2009年05月至2010年10月我院老年科住院的2型糖尿病患者51例,对照组15例。将51例糖尿病患者按照不同尿蛋白排泄率水平分为3组,临床蛋白尿组11例(UAER>200μg/min)、微量蛋白尿组19例(20μg≤UAER≤200μg/min)、正常蛋白尿组21例(UAER< 20μg/min),15例非糖尿病为对照组,酶联免疫分析法(ELISA法)测定脂肪酸结合蛋白(FABP),分析FABP的变化及与体重指数(BMI)、血脂、游离脂肪酸(N-EFA)、空腹血糖(FBS)、空腹胰岛素(FINS).血肌酐(Scr)、胰岛素抵抗指数(HOMA-IR),尿蛋白排泄率(UAER),内生肌酐清除率(Ccr)、肾小球滤过率(GFR)的关系。
结果：
1、一般资料比较：糖尿病各组及对照组一般资料均无统计学差异(P>0.05)。
2、不同尿蛋白排泄率水平组FABP有统计学差异(P<0.05)。FABP与UAER呈正相关(P<0.05)。
3、FABP与体重指数呈正相关(P<0.05),FABP与年龄、糖尿病病程、收缩压、舒张压均无相关性(P>0.05)。
4、糖尿病各组及对照组比较,TG、N-EFA均有统计学差异(P<0.05)。糖尿病各组FBS无统计学差异。各组患者TC、HDLLDL无统计学差异(P>0.05)。FABP与N-EFA、TG呈正相关,与HDL呈负相关(P<0.05),与FBS、TC、LDL无相关性(P>0.05)。
5、各组Scr、Ccr、GFR比较均有统计学差异(P<0.05)。FABP与Scr、Ccr、FR均无相关性(P>0.05)。
6、各组FINS、HOMA-IR比较均有统计学差异(P<0.05),FABP与FINS、HOMA-IR呈正相关(P<0.05)。
7、多元线性回归分析显示：FABP与NEFA、TG、BMI的关系密切,标准化回归系数分别为：0.608,0.277,0.105,P值0.000,0.009,0.045。UAER与N-EFA、FBS、HOMA-IR关系密切,标准化回归系数分别为：0.387,0.295,0.495,P值0.040,,0.032,0.000。
8、相对危险度分析显示：该人群FABP中位数为13.175ng/ml, FABP高值组(FABP>13.175ng/ml)患糖尿病肾病风险是低值组(FABP<13.175 ng/ml)患糖尿病肾病风险的4.033倍(95%CI=1.445-11.257,P=0.008)。
结论：
1、糖尿病肾病患者FABP浓度升高,FABP与游离脂肪酸、肥胖、脂质代谢紊乱、胰岛素抵抗等相关。
2、FABP浓度的升高可能增加了老年糖尿病患者肾病的风险。
Objectives
To determine the expression of serum FABP in elderly patients with diabetes, locate the contacts of the change of FABP and diabetic nephropathy related biochemical indicators and discuss the prediction value in diabetic nephropathy.
Materials and Methods
51 cases of elderly endocrinologlst hospitalized patients with type 2 diabetes were recruited from May 2009 to October 2010, and 15 cases without diabetes as the control group.51 cases of diabetes were divided into three groups in accordance with different urinary albumin excretion rates,11 cases with clinical proteinuria (UAER>200μg/min),19 cases with microalbuminuria (20μg/min≤UAER≤200μg/min),21 cases with normal albuminuria (UAER<20μg/min),15 cases of patients without diabetes as the control group. Determined the Fatty acid binding protein(FABP) by Enzyme-linked immunosorbent assay(ELISA), analysis the relationship between FABP and Body mass index(BMI), Blood fat, Non-esterified fatty acid (NEFA), Fast blood sugar(FBS), Fasting insulin(FINS), Insulin resistance index(HOMA-IR), Urinary albumin excretion rate(UAER), Serum creatinine (Scr), creatinine clearance (Ccr) and Glomerular filtration rate (GFR),
Results:
(1) General information Comparison:The general information among three diabetic groups and control group are not significant. (P>0.05).
(2) The FABP among four groups is statistically significant (P<0.05). FABP is positively correlated with UAER(P<0.05).
(3) FABP is positively correlated with BMI (P<0.05). FABP has no correlations with age, duration of diabetes, Systolic blood pressure and diastolic pressure (P> 0.05).
(4) The TG, N-EFA among three diabetics and control group are statistically significant (P<0.05). The FBS is not significant among three diabetics. The TC, HDL, LDL are not statistically significant among four groups(P>0.05). FABP is positively correlated with TG, N-EFA(P<0.05), and HDL-C negatively correlated (P<0.05), FABP has no significant correlations with TC, LDL-C (P> 0.05).
(5) The Scr. Ccr. GFR are statistically significant (P<0.05).FABP has no significant correlations with Scr, Ccr, GFR(P>0.05).
(6) The FINS, HOMA-IR are statistically significant (P<0.05). FABP is positively correlated with FINS, HOMA-IR(P< 0.05).
(7) Multiple linear regression analysis shows that:FABP is closely related to NEFA, TG, BMI. Standardized regression coefficients are respectively:0.608,0.277,0.105, P value:0.000,0.009,0.045. UAER is closely related EFA, FBS, HOMA-IR. Standardized regression coefficients are respectively:0.387,0.295,0.495, P value:0.040,0.032, 0.000.
(8) Relative risk analysis shows that:The median of FABP is 13.175ng/ml in this population. The risk of FABP high-value group (FABP>13.175ng/ml) suffer diabetic nephropathy is 4.033 times than low-value group(FABP<13.175ng/ml).(95%CI=1.445-11.257, P=0.008)
Conclusions:
(1) FABP elevates in diabetic patients with diabetic nephropathy, FABP has close relations with the free fatty acid, obesity, lipid metabolism, insulin resistance, etc.
(2) As the risk factors increases, the increase of fatty acid binding protein increases the risk of diabetic nephropathy of elderly diabetic patients.
本研究旨在测定老年糖尿病患者中血清脂肪酸结合蛋白(FABP)水平,分析糖尿病肾病患者FABP的变化及其他相关指标间的关系。探讨其对糖尿病肾病的预测的价值。
材料和方法：
选取2009年05月至2010年10月我院老年科住院的2型糖尿病患者51例,对照组15例。将51例糖尿病患者按照不同尿蛋白排泄率水平分为3组,临床蛋白尿组11例(UAER>200μg/min)、微量蛋白尿组19例(20μg≤UAER≤200μg/min)、正常蛋白尿组21例(UAER< 20μg/min),15例非糖尿病为对照组,酶联免疫分析法(ELISA法)测定脂肪酸结合蛋白(FABP),分析FABP的变化及与体重指数(BMI)、血脂、游离脂肪酸(N-EFA)、空腹血糖(FBS)、空腹胰岛素(FINS).血肌酐(Scr)、胰岛素抵抗指数(HOMA-IR),尿蛋白排泄率(UAER),内生肌酐清除率(Ccr)、肾小球滤过率(GFR)的关系。
结果：
1、一般资料比较：糖尿病各组及对照组一般资料均无统计学差异(P>0.05)。
2、不同尿蛋白排泄率水平组FABP有统计学差异(P<0.05)。FABP与UAER呈正相关(P<0.05)。
3、FABP与体重指数呈正相关(P<0.05),FABP与年龄、糖尿病病程、收缩压、舒张压均无相关性(P>0.05)。
4、糖尿病各组及对照组比较,TG、N-EFA均有统计学差异(P<0.05)。糖尿病各组FBS无统计学差异。各组患者TC、HDLLDL无统计学差异(P>0.05)。FABP与N-EFA、TG呈正相关,与HDL呈负相关(P<0.05),与FBS、TC、LDL无相关性(P>0.05)。
5、各组Scr、Ccr、GFR比较均有统计学差异(P<0.05)。FABP与Scr、Ccr、FR均无相关性(P>0.05)。
6、各组FINS、HOMA-IR比较均有统计学差异(P<0.05),FABP与FINS、HOMA-IR呈正相关(P<0.05)。
7、多元线性回归分析显示：FABP与NEFA、TG、BMI的关系密切,标准化回归系数分别为：0.608,0.277,0.105,P值0.000,0.009,0.045。UAER与N-EFA、FBS、HOMA-IR关系密切,标准化回归系数分别为：0.387,0.295,0.495,P值0.040,,0.032,0.000。
8、相对危险度分析显示：该人群FABP中位数为13.175ng/ml, FABP高值组(FABP>13.175ng/ml)患糖尿病肾病风险是低值组(FABP<13.175 ng/ml)患糖尿病肾病风险的4.033倍(95%CI=1.445-11.257,P=0.008)。
结论：
1、糖尿病肾病患者FABP浓度升高,FABP与游离脂肪酸、肥胖、脂质代谢紊乱、胰岛素抵抗等相关。
2、FABP浓度的升高可能增加了老年糖尿病患者肾病的风险。
Objectives
To determine the expression of serum FABP in elderly patients with diabetes, locate the contacts of the change of FABP and diabetic nephropathy related biochemical indicators and discuss the prediction value in diabetic nephropathy.
Materials and Methods
51 cases of elderly endocrinologlst hospitalized patients with type 2 diabetes were recruited from May 2009 to October 2010, and 15 cases without diabetes as the control group.51 cases of diabetes were divided into three groups in accordance with different urinary albumin excretion rates,11 cases with clinical proteinuria (UAER>200μg/min),19 cases with microalbuminuria (20μg/min≤UAER≤200μg/min),21 cases with normal albuminuria (UAER<20μg/min),15 cases of patients without diabetes as the control group. Determined the Fatty acid binding protein(FABP) by Enzyme-linked immunosorbent assay(ELISA), analysis the relationship between FABP and Body mass index(BMI), Blood fat, Non-esterified fatty acid (NEFA), Fast blood sugar(FBS), Fasting insulin(FINS), Insulin resistance index(HOMA-IR), Urinary albumin excretion rate(UAER), Serum creatinine (Scr), creatinine clearance (Ccr) and Glomerular filtration rate (GFR),
Results:
(1) General information Comparison:The general information among three diabetic groups and control group are not significant. (P>0.05).
(2) The FABP among four groups is statistically significant (P<0.05). FABP is positively correlated with UAER(P<0.05).
(3) FABP is positively correlated with BMI (P<0.05). FABP has no correlations with age, duration of diabetes, Systolic blood pressure and diastolic pressure (P> 0.05).
(4) The TG, N-EFA among three diabetics and control group are statistically significant (P<0.05). The FBS is not significant among three diabetics. The TC, HDL, LDL are not statistically significant among four groups(P>0.05). FABP is positively correlated with TG, N-EFA(P<0.05), and HDL-C negatively correlated (P<0.05), FABP has no significant correlations with TC, LDL-C (P> 0.05).
(5) The Scr. Ccr. GFR are statistically significant (P<0.05).FABP has no significant correlations with Scr, Ccr, GFR(P>0.05).
(6) The FINS, HOMA-IR are statistically significant (P<0.05). FABP is positively correlated with FINS, HOMA-IR(P< 0.05).
(7) Multiple linear regression analysis shows that:FABP is closely related to NEFA, TG, BMI. Standardized regression coefficients are respectively:0.608,0.277,0.105, P value:0.000,0.009,0.045. UAER is closely related EFA, FBS, HOMA-IR. Standardized regression coefficients are respectively:0.387,0.295,0.495, P value:0.040,0.032, 0.000.
(8) Relative risk analysis shows that:The median of FABP is 13.175ng/ml in this population. The risk of FABP high-value group (FABP>13.175ng/ml) suffer diabetic nephropathy is 4.033 times than low-value group(FABP<13.175ng/ml).(95%CI=1.445-11.257, P=0.008)
Conclusions:
(1) FABP elevates in diabetic patients with diabetic nephropathy, FABP has close relations with the free fatty acid, obesity, lipid metabolism, insulin resistance, etc.
(2) As the risk factors increases, the increase of fatty acid binding protein increases the risk of diabetic nephropathy of elderly diabetic patients.
引文
[1]Open HP, Krzyzanowska K, Mohlig M, et al. Effects of marked weight loss on plasma levels of adiponect in,markers of chronic subclinical inflammation and insulin resistance in morbidly obese women [J]. Int J Obes (Lond),2005,2(7): 766-771.
[2]梁静,多来提.糖尿病肾病患者转铁蛋自与β2微球蛋白和微量清蛋白的关系[J].检验医学与临床,2008,5(16)：971-973.
[3]Average JC, GansevootRT, HL, et al.An elevate urinary albumin excretion predicts denovo development of renal function impairment in the general population Kidney Int SuPP,2004,92:18-21.
[4]Klausenk, boreh-Jonhsen K, Feld-rasmussen B et al. very low levels of Microal buminuria are associated with increased risk of coronary heart disease and death independently of renal function hypertension, and diabetes[J]. Circulation,2004, 110(1):32-35.
[5]Ftp Y, Luo N, Their RL, ftp sat. Adiponectin promotes adipocyte diff erentiation, insulin sensitivity, and lipid accumulation [J]. J Lipid Res,2005, 46(7):1369-1379.
[6]Family A,Timbre K,Sunday T ftp sat. Urinary free fatty acids bound to albumin aggravate tubulointerstitial damage.Kidney Int,2002.62:1628-1637
[7]张连珊等FABP4在糖尿病大鼠肾脏中的表达及意义[A]；中华医学会病理学分会2009年学术年会论文汇编[C]
[8]Tortilla D, Dent C, Sunday T, ftp sat. Liver fatty acid-binding protein as a biomarker of acute kidney injury after cardiac surgery. Kidney Int,2008, 73:465-472.
[9]Kamijo-Ikemori A, Sugaya T, Kimura K. Urinary fatty acid binding protein in renal disease. Clin Chim Acta,2006,374:127.
[10]KazemiMR, M cDon ald CM, Sh igenaga JK, et a.l Adipocyte fatty acid binding protein expression and lipid accumulation are increased during activation of murine macrophages by toll-like receptor agonists [J]. Arterioscler Thromb V asc Bio,l 2005,25(6):1220-1224
[11]李红.糖尿病微血管病变发病机制和治疗靶点.浙江大学学报,2006,35(3)：232-237.
[12]LuisH.Canani, Clarissa CaPP, Daniel P.K. Ng, et al. The Fatty Acid-Binding Protein-2 A54T Polymorphism is associated with Renal Disease in Patients With Type 2 Diabetes. [J] Diabetes,2005,54:3326-3330.
[13]Chmurzynska A. The multigene family of fatty acid binding protein (FABP) Function, structure and polymorphism [J]. J App 1 Genent,2006,47 (1):39-48.
[14]Cabre A, Lozaro I, Girona J, et al. Fatty acid binding protein-4 is increased in metabolic syndrome and with thiazolidinedione treatment in diabetic patients. Atheroaclerosis,2007,195:e150-e158.
[15]Thomas R, Birgit S, Christain L, et al. Adipocyte fatty acid binding protein in obesity children and after weight loss. Metabolism Clinical and Experimental,2007,56:1735-41.
[16]Annette WK, Carolh HY. Aimin X, et al. Serum adipcyte fatty acid-binding protein as a new biomarker predicting the development of type 2 Diabetes. Diabete Care,2007,30(10):2667.
[17]Roden M. Blocking fatty acids mystery tour:a therapy for metabolic syndrome? Cell Metab.2007,6:89-91.
[18]Woywodt A,Bahlmann FH, De Groot k.et al.Circulating endothelial cells:life,death,detachment and repair of the endothelial cell layer.Nephrol Dial Thansplant,2002,17(10):1728-1730
[19]Veerkamp JH,Peetures RA,Maatman RG Structural and functional features of different types of cytoplasmic fatty acid-binding proteins. Biochim Biophys Actz,1991,1081:1-24
[20]Kamijo A, Kimura K, Sugaya T, Yamanouchi M, Hase H, Kaneko T, Hirata Y, Goto A, Fujita T, Omata M. Urinary free fatty acids bound to albumin aggravate tubulointerstitial damage. Kidney Int,2002,62:1628-1637.
[21]Dennis C.Y. Yeung, Aimin XU,et.al.Circulating Levels of Adipocyte and Epidermal Fatty Acid-Binding Proteins in Relation to Nephropathy Staging and Macrovascular Complications in Type 2 Diabetic Patients. Diabetes Care,2009, 32:132-134
[22]Cabre A, Lazaro I, Girona J, et al. Plasma fatty acid binding protein 4 increases with renal dysfunction in type 2 diabetic patients without microalbuminuria. Clin Chem, [Epub ahead of print].2008 Jan;54(1):181-7
[23]吴亚,魏宏莲等,血清脂肪细胞型脂肪酸结合蛋白测定在慢性原发性肾小球肾炎的临床意义；《临床荟萃》2009,12(20)：62-65
[24]Scheja L, Malowski L, Uysal KT, et al. Altered insulin secretion associated with reduced lipolytic efficiency in aP2 mice [J]. Diabetes,1999,48 (10):1987-1994.
[25]Maeda K, Cao H. Kono K, et al. Adipocyte/macrophage fatty acid binding proteins control integrated metabolic responses in obesity and diabetes[J]. Cell Metab,2005,1:107-119
[26]Maeda K, Uysal KT, Makow sk iL, et al. Role of the fatty acid binding protein mall in obesity and insulin resistance [J]. Diabetes,2003,52 (2):300-307
[27]Mohlig M, Weickert MO, Ghadanlgadai E, et al. Adipocyte fatty acid-binding protein is associated with markers of obesity. but is an unlikely link between obesity, insulin resistance, and hyperandrogenism in polycystic ovary syndrome women. Eur J Endocrino 1.2007 Aug; 157(2):195-200
[28]张敏英,张勉之,刘树松.2型糖尿病并发肾病的危险因素研究.中国慢性病预防与控制,2006,14(2)：78-81.
[29]张勉之.糖尿病性肾病的基础与临床[M].北京：中国医药科技出版社,2000.28-29.
[1]Shoelson SE, Herrero L, NaazA.Obesity, inflammation, and insulin Resistance, Gastroenterology,2007,132(6):2169-2180
[2]Reese Wagoner A, Thompson J, Banaszak L. Structural properties of the adipocyte lipid binding protein [J]. Biochim Biophys Acta,1999,1441 (2,3): 106-116.
[3]XuY, Iyengar S, RobertsRL, et a.l Primary culture model of peroxisome proliferators activated receptor gamma activity in prostate cancer cells[J]. JCell, Physio,l 2003,196(1):131-143.
[4]Chm urzyn ska A. Themulti gene family of fatty acid binding protein(FABPs): Function, structure andpolymorph ism [J]. J Appl Genent,2006,47(1):39-48.
[5]Reese Wagoner A, Thompson J, Banaszak L. Structural properties of the adipocyte lipid binding protein [J]. Bioch im Biophys Acta,1999,1441(2-3): 106-116.
[6]Knowlton AA, Burrier RE, Brecher P. Rabbit heart fatty acid binding protein[J]. Circul Res,1989,65(4):981-988
[7]Turcotte LP, Ilattri Y, Ohba Y, et al. Fasting increases plasma membrane fatty Acid bingding protein (FABP) in red skeletal muscle[J]. Mol Cell Biocchim, 1997,166(1-2):153-158
[8]Kohaar Ⅰ, Hussain S, Thakur N, et al. Association between human leukocyte antigen class Ⅱ alleles and human papillomavirus-mediated cervical cancer in Indian women[J]. Hum Immunol,2009,70(4):222-229.
[9]Zhao T, Nzkebaloudou M, Lv J. Ala54Thr polymorphism of fatty acid-bind ingprotein 2 gene and fasting blood lipids [J]. A meta-analysis,2010, 10(2):461-467.
[10]Tso A W, Xu A, Sham P C, etal. Serum adipocyte fatty acid-binding protein as an new biomarker predicting the development of type 2 diabetes:A 102 year Prospective study in Chinesecohort[J]. DiabetesCare,2007,30 (10):2667-2672.
[11]Furuhashi M, Tuncman G, Gorglun C Z, et al. Treatment of diabetes and a theroscleros is by inhibiting fatty acid binding protein aP2 [J]. Nature,2007,447 (7147):959-965.
[12]Xu A, Wang Y, Xu JY, et al. Adipocyte fatty acid binding protein is a plasma biomarker closely associated with obesity and metabolic syndrome. Clin Chem, 2006.52:405-413.
[13]Xu A, Wang Y, Xu JY, et al. Adipocyte fatty acid binding protein is a plasma biomarker closely associated with obesity and metabolic syndrome. Clin Chem, 2006,52:405-413.
[14]Arici M, Chana R, Lewington A, et al. Stimulation of proximal tubular cell apoptosis by albumin bound fatty acids mediated by peroxisome proliferator activated receptor-gamma. J Am Soc Nephrol,2003,14:17-27.
[15]张连珊,吴亚,魏宏莲等,血清脂肪细胞型脂肪酸结合蛋白测定对慢性肾脏病的诊断价值,2009年脂质代谢与器官损害国际学术研讨会；重庆医科大学主办；中国重庆；2009-11-26.
[16]Cabre A, Ldzam I, Girona J, et al. Plasma fatty acid_binding protein 4 increases with renal dysfunction in type 2 diabetic patients without microalbuminuria. Clin Chem. [Epub ahead of print].2008 Jan;54(1):181-7
[17]Kamijo-Ikemori A, Sugaya T, Kimura K. Urinary fatty acid binding protein in renal disease. Clin Chim Acta 2006;374:1-7
[18]Kamijo A, Kimura K, Sugaya T, Yamanouchi M,Hikawa A, Hirano N, Hirata Y,Goto A, Omata M.Urinary fatty acid-binding protein as a new clinical marker of the progression of chronic renal disease. J Lab Clin Med 2004; 143: 23-30
[19]Kamijo A, Sugaya T, Hikawa A, Yamanouchi M, Hirata Y, Ishimitsu T, Numabe A, Takagi M, Hayakawa H, Tabei F, Sugimoto T, Mise N, Kimura K. Clinical evaluation of urinary excretion of livertype fatty acid-binding protein as a marker for the monitoring of chronic kidney disease:a multicenter trial. J Lab Clin Med 2005; 145:125-133
[20]Nakamura T, Sugaya T, Kawagoe Y, Ueda Y, Osada S, Koide H. Urinary liver-type fatty acid-binding protein levels for differential diagnosis of idiopathic focal glomerulosclerosis and minor glomerular abnormalities and effect of low-density lipoprotein apheresis. Clin Nephrol 2006; 65:1-6
[21]Nakamura T, Sugaya T, Node K, Ueda Y, Koide H. Urinary excretion of liver-type fatty acid-binding protein in contrast medium-induced nephropathy. Am J Kidney Dis 2006; 47:439-444
[22]Yamamoto T, Noiri E, Ono Y, Doi K, Negishi K, Kamijo A, Kimura K, Fujita T,Kinukawa T, Taniguchi H, Nakamura K, Goto M, Shinozaki N,Ohshima S, Sugaya T. Renal L-type fatty acid-binding protein in acute ischemic injury. J Am Soc Nephrol 2007; 18:2894-2902
[23]leeEJ, LeeWY ParkCY, etal. The association of serum adipocyte fatty acid binding protein with coronary artery disease in Korean adults. EurJ Endocrinol, 2009,160(2):165-172.
[24]富路,程丽娟,高倩萍等,脂肪酸结合蛋白在急性心肌梗死早期诊断中的临床意义,中国急救医学,2007,27(9)：783-785.
[25]明媚,孟祥志.早期心肌缺血心脏型脂肪酸结合蛋白的免疫组织化学观察.法医学杂志,2004；20(1)：15-18.
[26]衣志勇,李小鹰等,急性心肌梗死心肌型脂肪酸结合蛋白的动态变化.中华老年心脑血管病杂志,2004；6(3)：151-153.
[27]Komamura K,Sasaki T,Hanatani A,et al.Heart-type fatty acid binding protein is a novel prognostic marker in patients with non-ischaemic dilated cardiomyopathy[J]. Heart,2006,92(5):615-618.
[28]单岩,张谦,朱慧琪H-FABP评价先心病患儿术中心肌缺血-再灌注损伤的价值仁[J].山东医药,2004,44(33)：8-9.
[29]Shahid H, Khan.Liver fatty acid binding Protein:specific mediator of the mitogenesis induce by two classes of carcinogenic peroxisome proliferators.Proc Natl Acad Sci USA,1994,91:848-852.
[30]Gromova I, Gromov P, W olfH, et a.l Protein abundancy and mRNA levels of The adipocyte type fatty acid binding protein correlate in noninvasive and invasive bladder transitional cell carcinomas[J]. International journal of oncology,1998,13 (2):379-83.
[31]Jing C, Beesley C, Foster CS, etal.Human cutaneous fatty acid-binding protein Induces metastasis by up-regulating the expression of vascular endothelial growth factor gene in rat Rama 37 modelcells.CancerRes,2001, 61:4357-4364.
[32]JingC, BeesleyC, FosterCS, etal.Identification of the messenger RNA for human cutaneous Fatty acid-binding protein as a metastasis inducer Cancer Res,2000, 60:2390-2398.
[33]LamDC, XuA, LamKS, etal.Serum adipocyte fatty acid binding protein level is elevated in severe OSA and correlate with insulin resistance[J].EurResPirJ, 2009,33:346-351.
[34]PeetersRA, VeerkamPJll, DemelRA.Are fatty acid binding Proteins involved in fatty Acid transfer?Bioehim Biophys Acta1989:1002:8-13.
[35]LamersJM, HulsmannWC.Inhibitionof(Na-K)stimulated ATP ase of heart by fatty acids, JMol Cell Cardiol 1977:9:343-346.
[36]LiedtkeAJ, NellisS, NeelyJR.Effects of excess free fatty acids on mechanical and metabolic function in normal and ischcemic myocardium in swine.Circ Res 1978, 4:652-61.
[2]梁静,多来提.糖尿病肾病患者转铁蛋自与β2微球蛋白和微量清蛋白的关系[J].检验医学与临床,2008,5(16)：971-973.
[3]Average JC, GansevootRT, HL, et al.An elevate urinary albumin excretion predicts denovo development of renal function impairment in the general population Kidney Int SuPP,2004,92:18-21.
[4]Klausenk, boreh-Jonhsen K, Feld-rasmussen B et al. very low levels of Microal buminuria are associated with increased risk of coronary heart disease and death independently of renal function hypertension, and diabetes[J]. Circulation,2004, 110(1):32-35.
[5]Ftp Y, Luo N, Their RL, ftp sat. Adiponectin promotes adipocyte diff erentiation, insulin sensitivity, and lipid accumulation [J]. J Lipid Res,2005, 46(7):1369-1379.
[6]Family A,Timbre K,Sunday T ftp sat. Urinary free fatty acids bound to albumin aggravate tubulointerstitial damage.Kidney Int,2002.62:1628-1637
[7]张连珊等FABP4在糖尿病大鼠肾脏中的表达及意义[A]；中华医学会病理学分会2009年学术年会论文汇编[C]
[8]Tortilla D, Dent C, Sunday T, ftp sat. Liver fatty acid-binding protein as a biomarker of acute kidney injury after cardiac surgery. Kidney Int,2008, 73:465-472.
[9]Kamijo-Ikemori A, Sugaya T, Kimura K. Urinary fatty acid binding protein in renal disease. Clin Chim Acta,2006,374:127.
[10]KazemiMR, M cDon ald CM, Sh igenaga JK, et a.l Adipocyte fatty acid binding protein expression and lipid accumulation are increased during activation of murine macrophages by toll-like receptor agonists [J]. Arterioscler Thromb V asc Bio,l 2005,25(6):1220-1224
[11]李红.糖尿病微血管病变发病机制和治疗靶点.浙江大学学报,2006,35(3)：232-237.
[12]LuisH.Canani, Clarissa CaPP, Daniel P.K. Ng, et al. The Fatty Acid-Binding Protein-2 A54T Polymorphism is associated with Renal Disease in Patients With Type 2 Diabetes. [J] Diabetes,2005,54:3326-3330.
[13]Chmurzynska A. The multigene family of fatty acid binding protein (FABP) Function, structure and polymorphism [J]. J App 1 Genent,2006,47 (1):39-48.
[14]Cabre A, Lozaro I, Girona J, et al. Fatty acid binding protein-4 is increased in metabolic syndrome and with thiazolidinedione treatment in diabetic patients. Atheroaclerosis,2007,195:e150-e158.
[15]Thomas R, Birgit S, Christain L, et al. Adipocyte fatty acid binding protein in obesity children and after weight loss. Metabolism Clinical and Experimental,2007,56:1735-41.
[16]Annette WK, Carolh HY. Aimin X, et al. Serum adipcyte fatty acid-binding protein as a new biomarker predicting the development of type 2 Diabetes. Diabete Care,2007,30(10):2667.
[17]Roden M. Blocking fatty acids mystery tour:a therapy for metabolic syndrome? Cell Metab.2007,6:89-91.
[18]Woywodt A,Bahlmann FH, De Groot k.et al.Circulating endothelial cells:life,death,detachment and repair of the endothelial cell layer.Nephrol Dial Thansplant,2002,17(10):1728-1730
[19]Veerkamp JH,Peetures RA,Maatman RG Structural and functional features of different types of cytoplasmic fatty acid-binding proteins. Biochim Biophys Actz,1991,1081:1-24
[20]Kamijo A, Kimura K, Sugaya T, Yamanouchi M, Hase H, Kaneko T, Hirata Y, Goto A, Fujita T, Omata M. Urinary free fatty acids bound to albumin aggravate tubulointerstitial damage. Kidney Int,2002,62:1628-1637.
[21]Dennis C.Y. Yeung, Aimin XU,et.al.Circulating Levels of Adipocyte and Epidermal Fatty Acid-Binding Proteins in Relation to Nephropathy Staging and Macrovascular Complications in Type 2 Diabetic Patients. Diabetes Care,2009, 32:132-134
[22]Cabre A, Lazaro I, Girona J, et al. Plasma fatty acid binding protein 4 increases with renal dysfunction in type 2 diabetic patients without microalbuminuria. Clin Chem, [Epub ahead of print].2008 Jan;54(1):181-7
[23]吴亚,魏宏莲等,血清脂肪细胞型脂肪酸结合蛋白测定在慢性原发性肾小球肾炎的临床意义；《临床荟萃》2009,12(20)：62-65
[24]Scheja L, Malowski L, Uysal KT, et al. Altered insulin secretion associated with reduced lipolytic efficiency in aP2 mice [J]. Diabetes,1999,48 (10):1987-1994.
[25]Maeda K, Cao H. Kono K, et al. Adipocyte/macrophage fatty acid binding proteins control integrated metabolic responses in obesity and diabetes[J]. Cell Metab,2005,1:107-119
[26]Maeda K, Uysal KT, Makow sk iL, et al. Role of the fatty acid binding protein mall in obesity and insulin resistance [J]. Diabetes,2003,52 (2):300-307
[27]Mohlig M, Weickert MO, Ghadanlgadai E, et al. Adipocyte fatty acid-binding protein is associated with markers of obesity. but is an unlikely link between obesity, insulin resistance, and hyperandrogenism in polycystic ovary syndrome women. Eur J Endocrino 1.2007 Aug; 157(2):195-200
[28]张敏英,张勉之,刘树松.2型糖尿病并发肾病的危险因素研究.中国慢性病预防与控制,2006,14(2)：78-81.
[29]张勉之.糖尿病性肾病的基础与临床[M].北京：中国医药科技出版社,2000.28-29.
[1]Shoelson SE, Herrero L, NaazA.Obesity, inflammation, and insulin Resistance, Gastroenterology,2007,132(6):2169-2180
[2]Reese Wagoner A, Thompson J, Banaszak L. Structural properties of the adipocyte lipid binding protein [J]. Biochim Biophys Acta,1999,1441 (2,3): 106-116.
[3]XuY, Iyengar S, RobertsRL, et a.l Primary culture model of peroxisome proliferators activated receptor gamma activity in prostate cancer cells[J]. JCell, Physio,l 2003,196(1):131-143.
[4]Chm urzyn ska A. Themulti gene family of fatty acid binding protein(FABPs): Function, structure andpolymorph ism [J]. J Appl Genent,2006,47(1):39-48.
[5]Reese Wagoner A, Thompson J, Banaszak L. Structural properties of the adipocyte lipid binding protein [J]. Bioch im Biophys Acta,1999,1441(2-3): 106-116.
[6]Knowlton AA, Burrier RE, Brecher P. Rabbit heart fatty acid binding protein[J]. Circul Res,1989,65(4):981-988
[7]Turcotte LP, Ilattri Y, Ohba Y, et al. Fasting increases plasma membrane fatty Acid bingding protein (FABP) in red skeletal muscle[J]. Mol Cell Biocchim, 1997,166(1-2):153-158
[8]Kohaar Ⅰ, Hussain S, Thakur N, et al. Association between human leukocyte antigen class Ⅱ alleles and human papillomavirus-mediated cervical cancer in Indian women[J]. Hum Immunol,2009,70(4):222-229.
[9]Zhao T, Nzkebaloudou M, Lv J. Ala54Thr polymorphism of fatty acid-bind ingprotein 2 gene and fasting blood lipids [J]. A meta-analysis,2010, 10(2):461-467.
[10]Tso A W, Xu A, Sham P C, etal. Serum adipocyte fatty acid-binding protein as an new biomarker predicting the development of type 2 diabetes:A 102 year Prospective study in Chinesecohort[J]. DiabetesCare,2007,30 (10):2667-2672.
[11]Furuhashi M, Tuncman G, Gorglun C Z, et al. Treatment of diabetes and a theroscleros is by inhibiting fatty acid binding protein aP2 [J]. Nature,2007,447 (7147):959-965.
[12]Xu A, Wang Y, Xu JY, et al. Adipocyte fatty acid binding protein is a plasma biomarker closely associated with obesity and metabolic syndrome. Clin Chem, 2006.52:405-413.
[13]Xu A, Wang Y, Xu JY, et al. Adipocyte fatty acid binding protein is a plasma biomarker closely associated with obesity and metabolic syndrome. Clin Chem, 2006,52:405-413.
[14]Arici M, Chana R, Lewington A, et al. Stimulation of proximal tubular cell apoptosis by albumin bound fatty acids mediated by peroxisome proliferator activated receptor-gamma. J Am Soc Nephrol,2003,14:17-27.
[15]张连珊,吴亚,魏宏莲等,血清脂肪细胞型脂肪酸结合蛋白测定对慢性肾脏病的诊断价值,2009年脂质代谢与器官损害国际学术研讨会；重庆医科大学主办；中国重庆；2009-11-26.
[16]Cabre A, Ldzam I, Girona J, et al. Plasma fatty acid_binding protein 4 increases with renal dysfunction in type 2 diabetic patients without microalbuminuria. Clin Chem. [Epub ahead of print].2008 Jan;54(1):181-7
[17]Kamijo-Ikemori A, Sugaya T, Kimura K. Urinary fatty acid binding protein in renal disease. Clin Chim Acta 2006;374:1-7
[18]Kamijo A, Kimura K, Sugaya T, Yamanouchi M,Hikawa A, Hirano N, Hirata Y,Goto A, Omata M.Urinary fatty acid-binding protein as a new clinical marker of the progression of chronic renal disease. J Lab Clin Med 2004; 143: 23-30
[19]Kamijo A, Sugaya T, Hikawa A, Yamanouchi M, Hirata Y, Ishimitsu T, Numabe A, Takagi M, Hayakawa H, Tabei F, Sugimoto T, Mise N, Kimura K. Clinical evaluation of urinary excretion of livertype fatty acid-binding protein as a marker for the monitoring of chronic kidney disease:a multicenter trial. J Lab Clin Med 2005; 145:125-133
[20]Nakamura T, Sugaya T, Kawagoe Y, Ueda Y, Osada S, Koide H. Urinary liver-type fatty acid-binding protein levels for differential diagnosis of idiopathic focal glomerulosclerosis and minor glomerular abnormalities and effect of low-density lipoprotein apheresis. Clin Nephrol 2006; 65:1-6
[21]Nakamura T, Sugaya T, Node K, Ueda Y, Koide H. Urinary excretion of liver-type fatty acid-binding protein in contrast medium-induced nephropathy. Am J Kidney Dis 2006; 47:439-444
[22]Yamamoto T, Noiri E, Ono Y, Doi K, Negishi K, Kamijo A, Kimura K, Fujita T,Kinukawa T, Taniguchi H, Nakamura K, Goto M, Shinozaki N,Ohshima S, Sugaya T. Renal L-type fatty acid-binding protein in acute ischemic injury. J Am Soc Nephrol 2007; 18:2894-2902
[23]leeEJ, LeeWY ParkCY, etal. The association of serum adipocyte fatty acid binding protein with coronary artery disease in Korean adults. EurJ Endocrinol, 2009,160(2):165-172.
[24]富路,程丽娟,高倩萍等,脂肪酸结合蛋白在急性心肌梗死早期诊断中的临床意义,中国急救医学,2007,27(9)：783-785.
[25]明媚,孟祥志.早期心肌缺血心脏型脂肪酸结合蛋白的免疫组织化学观察.法医学杂志,2004；20(1)：15-18.
[26]衣志勇,李小鹰等,急性心肌梗死心肌型脂肪酸结合蛋白的动态变化.中华老年心脑血管病杂志,2004；6(3)：151-153.
[27]Komamura K,Sasaki T,Hanatani A,et al.Heart-type fatty acid binding protein is a novel prognostic marker in patients with non-ischaemic dilated cardiomyopathy[J]. Heart,2006,92(5):615-618.
[28]单岩,张谦,朱慧琪H-FABP评价先心病患儿术中心肌缺血-再灌注损伤的价值仁[J].山东医药,2004,44(33)：8-9.
[29]Shahid H, Khan.Liver fatty acid binding Protein:specific mediator of the mitogenesis induce by two classes of carcinogenic peroxisome proliferators.Proc Natl Acad Sci USA,1994,91:848-852.
[30]Gromova I, Gromov P, W olfH, et a.l Protein abundancy and mRNA levels of The adipocyte type fatty acid binding protein correlate in noninvasive and invasive bladder transitional cell carcinomas[J]. International journal of oncology,1998,13 (2):379-83.
[31]Jing C, Beesley C, Foster CS, etal.Human cutaneous fatty acid-binding protein Induces metastasis by up-regulating the expression of vascular endothelial growth factor gene in rat Rama 37 modelcells.CancerRes,2001, 61:4357-4364.
[32]JingC, BeesleyC, FosterCS, etal.Identification of the messenger RNA for human cutaneous Fatty acid-binding protein as a metastasis inducer Cancer Res,2000, 60:2390-2398.
[33]LamDC, XuA, LamKS, etal.Serum adipocyte fatty acid binding protein level is elevated in severe OSA and correlate with insulin resistance[J].EurResPirJ, 2009,33:346-351.
[34]PeetersRA, VeerkamPJll, DemelRA.Are fatty acid binding Proteins involved in fatty Acid transfer?Bioehim Biophys Acta1989:1002:8-13.
[35]LamersJM, HulsmannWC.Inhibitionof(Na-K)stimulated ATP ase of heart by fatty acids, JMol Cell Cardiol 1977:9:343-346.
[36]LiedtkeAJ, NellisS, NeelyJR.Effects of excess free fatty acids on mechanical and metabolic function in normal and ischcemic myocardium in swine.Circ Res 1978, 4:652-61.