视网膜色素变性患者血清脂肪代谢的异常变化
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摘要
目的对比原发性视网膜色素变性(primary retinitis pigmentosa,PRP)、结晶样视网膜色素变性(bietti crystalline dystrophy,BCD)患者血清中游离脂肪酸(free fatty acid,FFA)及心型脂肪酸结合蛋白(heart fatty acid binding proteins,HFABP)含量的变化,为探索其发病机理和防治提供参考。方法采用回顾性研究方法,纳入临床诊断标准的首都医科大学附属北京同仁医院眼科中心门诊PRP患者80例,BCD患者50例,与正常对照组60例进行比较,按盲法由专业技术人员完成血清中FFA及HFABP浓度检查。分析PRP、BCD患者体内FFA和HFABP含量与正常对照组的差别。结果 PRP患者血清FFA、HFABP浓度分别为(0. 547±0. 214) mmol·L~(-1)、(3. 594±0. 791) mmol·L~(-1); BCD患者血清FFA、HFABP浓度分别为(0. 529±0. 108) mmol·L~(-1)、(4. 237±1. 258) mmol·L~(-1);正常对照组的FFA、HFABP浓度分别为(0. 386±0. 251) mmol·L~(-1)、(5. 261±1. 471) mmol·L~(-1)。与正常对照组比较,两种退行性视网膜疾病的FFA浓度显著升高(均为P <0. 05),而HFABP浓度显著降低(均为P <0. 05)。结论 PRP及BCD患者血清FFA及HFABP浓度存在异常变化,提示了其可能与退行性视网膜疾病的发生发展有关,对疾病的治疗具有一定的指导意义。
Objective To analyze the serum concentration alteration of free fatty acid (FFA) and heart fatty acid binding proteins (HFABP) of primary retinitis pigmentosa(PRP) and bietti crystalline dystrophy(BCD) to provide a reference for exploring the pathogenesis and prevention of retinal degenerative diseases. Methods Retrospective research methods were implemented. A total of 60 individuals as normal control group, 80 patients with PRP and 50 patients with BCD were enrolled from the Outpatient Department of Beijing Tongren Hospital affiliated to Capital Medical University. The serum FFA and HFABP concentration were checked by professional technicians and the differences in FFA and HFABP levels between patients and controls were analyzed in a blinded manner. Results The concentrations of serum FFA and HFABP in patients with PRP were(0. 547 ± 0. 2 1 4) mmol · L~(-1) and(3.594 ±0.791) mmol· L~(-1),respectively. While the concentrations of serum FFA and HFABP in patients with BCD were(0. 529 ±0. 108) mmol ·L~(-1) and(4. 23 7 ± 1. 25 8) mmol · L~(-1) respectively. The FFA and HFABP concentrations in the normal control group were (0.386 ±0. 251) mmol · L~(-1) and(5.261 ±1.471) mmol · L~(-1),respectively. Compared with the normal control group, the FFA concentrations in patients with PRP and BCD were significantly increased(both P <0. 05), while the HFABP concentration were significantly decreased (both P < 0. 05). Conclusion Abnormal changes in the serum FFA and HFABP in patients with PRP and BCD suggest that it may be related to the occurrence and development of degenerative retinal diseases, which can provide a significance reference for the treatment of diseases.
Objective To analyze the serum concentration alteration of free fatty acid (FFA) and heart fatty acid binding proteins (HFABP) of primary retinitis pigmentosa(PRP) and bietti crystalline dystrophy(BCD) to provide a reference for exploring the pathogenesis and prevention of retinal degenerative diseases. Methods Retrospective research methods were implemented. A total of 60 individuals as normal control group, 80 patients with PRP and 50 patients with BCD were enrolled from the Outpatient Department of Beijing Tongren Hospital affiliated to Capital Medical University. The serum FFA and HFABP concentration were checked by professional technicians and the differences in FFA and HFABP levels between patients and controls were analyzed in a blinded manner. Results The concentrations of serum FFA and HFABP in patients with PRP were(0. 547 ± 0. 2 1 4) mmol · L~(-1) and(3.594 ±0.791) mmol· L~(-1),respectively. While the concentrations of serum FFA and HFABP in patients with BCD were(0. 529 ±0. 108) mmol ·L~(-1) and(4. 23 7 ± 1. 25 8) mmol · L~(-1) respectively. The FFA and HFABP concentrations in the normal control group were (0.386 ±0. 251) mmol · L~(-1) and(5.261 ±1.471) mmol · L~(-1),respectively. Compared with the normal control group, the FFA concentrations in patients with PRP and BCD were significantly increased(both P <0. 05), while the HFABP concentration were significantly decreased (both P < 0. 05). Conclusion Abnormal changes in the serum FFA and HFABP in patients with PRP and BCD suggest that it may be related to the occurrence and development of degenerative retinal diseases, which can provide a significance reference for the treatment of diseases.
引文
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[11]LIU Y,ZHANG D,HU J,LIU G,CHEN J,SUN L,et al.Visible light-induced lipid peroxidation of unsaturated fatty acids in the retina and the inhibitory effects of blueberry polyphenols[J].JAgric Food Chem,2015,63(42):9295-9305.
[12]FIGUEROA J D,SERRANO-ILLAN M,LICERO J,CORDERO K,MIRANDA J D,De LEON M.Fatty acid binding protein 5 modulates docosahexaenoic acid-induced recovery in rats undergoing spinal cord injury[J].J Neurotrauma,2016,33(15):1436-1449.
[13]HOWIE D,TEN B A,NECULA A S,COBBOLD S P,WALDMA-NN H.The role of lipid metabolism in T lymphocyte differentiation and survival[J].Front Immunol,2017,8:1949.
[14]SELLNER P.Developmental regulation of fatty acid binding protein in neural tissue[J].Dev Dyn,1994,200(4):333-339.
[15]MURPHY E J.Ether lipids and their elusive function in the nervous system:a role for plasmalogens:An Editorial Highlight for‘Reduced muscle strength in ether lipid-deficient mice is accompanied by altered development and function of the neuromuscular junction’on page 569[J].J Neurochem,2017,143(5):463-466.
[16]WIDSTROM R L,NORRIS A W,SPECTOR A A.Binding of cytochrome P450 monooxygenase and lipoxygenase pathway products by heart fatty acid-binding protein[J].Biochemistry,2001,40(4):1070-1076.
[17]WILSON D J,WELEBER R G,KLEIN M L,WELCH R B,GREEN WR.Bietti’s crystalline dystrophy.A clinicopathologic correlative study[J].Arch Ophthalmol,1989,107(2):213-221.
[18]BLAAK E.Gender differences in fat metabolism[J].Curr Opin Clin Nutr Metab Care,2001,4(6):499-502.
[19]LEE J,JIAO X,HEJTMANCIK J F,KAISER-KUPFER M,GAHL WA,MARKELLO T C,et al.The metabolism of fatty acids in human Bietti crystalline dystrophy[J].Invest Ophthalmol Vis Sci,2001,42(8):1707-1714.
[20]LO V A,SAKAYORI N,HACHEM M,BELKOUCH M,PICQ M,LAGARDE M,et al.Mechanisms of DHA transport to the brain and potential therapy to neurodegenerative diseases[J].Biochimie,2016,130:163-167.
[21]SU X,TAN Q S,PARIKH B H,TAN A,MEHTA M N,SIA W Y,et al.Characterization of fatty acid binding protein 7(FABP7)in the murine retina[J].Invest Ophthalmol Vis Sci,2016,57(7):3397-3408.
[22]VENKATESH A,MA S,LE YZ,HALL M N,RUEGG M A,PUNZOC.Activated m TORC1 promotes long-term cone survival in retinitis pigmentosa mice[J].J Clin Invest,2015,125(4):1446-1458.
[23]NARAYAN D S,WOOD J P,CHIDLOW G,CASSON R J.A review of the mechanisms of cone degeneration in retinitis pigmentosa[J].Acta Ophthalmol,2016,94(8):748-754.
[24]MAUDE M B,ANDERSON E O,ANDERSON R E.Polyunsaturated fatty acids are lower in blood lipids of Usher’s type I but not Usher’s typeⅡ[J].Invest Ophthalmol Vis Sci,1998,39(11):2164-2166.
[2]LI M D,HE T,SUN X W,YIN X B,LI G L.Characteristics of serum lipids changes in primary retinitis pigmentosa patients[J].Rec Adv Ophthalmol,2014,34(3):236-238.李孟达,何婷,孙晓伟,殷晓贝,李根林.原发性视网膜色素变性患者血清脂蛋白含量的变化[J].眼科新进展,2014,34(3):236-238.
[3]LI M D,YIN X B,HE T,SUN X W,LI G L.Changes of serum lipids in patients with Bietti crystalline dystrophy[J].Chin J Exp Ophthalmol,2015,33(1):47-50.李孟达,殷晓贝,何婷,孙晓伟,李根林.结晶样视网膜色素变性患者血脂浓度的变化[J].中华实验眼科杂志,2015,33(1):47-50.
[4]LI S,LEE J,ZHOU Y,GORDON W C,HILL J M,BAZAN NG,et al.Fatty acid transport protein 4(FATP4)prevents light-induced degeneration of cone and rod photoreceptors by inhibiting RPE65 isomerase[J].J Neurosci,2013,33(7):3178-3189.
[5]BAYERLE-EDER M,POLSKA E,KOPF A,RODEN M,WALDHA-USL W,PLEINER H,et al.Free fatty acids exert a greater effect on ocular and skin blood flow than triglycerides in healthy subjects[J].Eur J Clin Invest,2004,34(8):519-526.
[6]BIRGER Y,BLUMENFELD O,BARTOV E,BURGANSKY-ELI-ASH Z.Reduced retinal blood flow-velocity in severe hyperlipidemia measured by the retinal function imager[J].Graefes Arch Clin Exp Ophthalmol,2011,249(10):1587-1590.
[7]YOKOI Y,NAKAZAWA M,MIZUKOSHI S,SATO K,USUI T,TAKEUCHI K.Crystal deposits on the lens capsules in Bietti crystalline corneoretinal dystrophy associated with a mutation in the CYP4 V2 gene[J].Acta Ophthalmol,2010,88(5):607-609.
[8]RICHARDS B W,BRODSTEIN D E,NUSSBAUM J J,FEREN-CZJ R,MAEDA K,WEISS L.Autosomal dominant crystalline dystrophy[J].Ophthalmology,1991,98(5):658-665.
[9]ROSSI S,TESTA F,LI A,YAYLACIOGLU F,GESUALDO C,HE-JTMANCIK J F,et al.Clinical and genetic features in Italian Bietti crystalline dystrophy patients[J].Br J Ophthalmol,2013,97(2):174-179.
[10]MARTIN R E,ELLIOTT M H,BRUSH R S,ANDERSON R E.Detailed characterization of the lipid composition of detergent-resistant membranes from photoreceptor rod outer segment membranes[J].Invest Ophthalmol Vis Sci,2005,46(4):1147-1154.
[11]LIU Y,ZHANG D,HU J,LIU G,CHEN J,SUN L,et al.Visible light-induced lipid peroxidation of unsaturated fatty acids in the retina and the inhibitory effects of blueberry polyphenols[J].JAgric Food Chem,2015,63(42):9295-9305.
[12]FIGUEROA J D,SERRANO-ILLAN M,LICERO J,CORDERO K,MIRANDA J D,De LEON M.Fatty acid binding protein 5 modulates docosahexaenoic acid-induced recovery in rats undergoing spinal cord injury[J].J Neurotrauma,2016,33(15):1436-1449.
[13]HOWIE D,TEN B A,NECULA A S,COBBOLD S P,WALDMA-NN H.The role of lipid metabolism in T lymphocyte differentiation and survival[J].Front Immunol,2017,8:1949.
[14]SELLNER P.Developmental regulation of fatty acid binding protein in neural tissue[J].Dev Dyn,1994,200(4):333-339.
[15]MURPHY E J.Ether lipids and their elusive function in the nervous system:a role for plasmalogens:An Editorial Highlight for‘Reduced muscle strength in ether lipid-deficient mice is accompanied by altered development and function of the neuromuscular junction’on page 569[J].J Neurochem,2017,143(5):463-466.
[16]WIDSTROM R L,NORRIS A W,SPECTOR A A.Binding of cytochrome P450 monooxygenase and lipoxygenase pathway products by heart fatty acid-binding protein[J].Biochemistry,2001,40(4):1070-1076.
[17]WILSON D J,WELEBER R G,KLEIN M L,WELCH R B,GREEN WR.Bietti’s crystalline dystrophy.A clinicopathologic correlative study[J].Arch Ophthalmol,1989,107(2):213-221.
[18]BLAAK E.Gender differences in fat metabolism[J].Curr Opin Clin Nutr Metab Care,2001,4(6):499-502.
[19]LEE J,JIAO X,HEJTMANCIK J F,KAISER-KUPFER M,GAHL WA,MARKELLO T C,et al.The metabolism of fatty acids in human Bietti crystalline dystrophy[J].Invest Ophthalmol Vis Sci,2001,42(8):1707-1714.
[20]LO V A,SAKAYORI N,HACHEM M,BELKOUCH M,PICQ M,LAGARDE M,et al.Mechanisms of DHA transport to the brain and potential therapy to neurodegenerative diseases[J].Biochimie,2016,130:163-167.
[21]SU X,TAN Q S,PARIKH B H,TAN A,MEHTA M N,SIA W Y,et al.Characterization of fatty acid binding protein 7(FABP7)in the murine retina[J].Invest Ophthalmol Vis Sci,2016,57(7):3397-3408.
[22]VENKATESH A,MA S,LE YZ,HALL M N,RUEGG M A,PUNZOC.Activated m TORC1 promotes long-term cone survival in retinitis pigmentosa mice[J].J Clin Invest,2015,125(4):1446-1458.
[23]NARAYAN D S,WOOD J P,CHIDLOW G,CASSON R J.A review of the mechanisms of cone degeneration in retinitis pigmentosa[J].Acta Ophthalmol,2016,94(8):748-754.
[24]MAUDE M B,ANDERSON E O,ANDERSON R E.Polyunsaturated fatty acids are lower in blood lipids of Usher’s type I but not Usher’s typeⅡ[J].Invest Ophthalmol Vis Sci,1998,39(11):2164-2166.