明目消朦片联合雷珠单抗治疗湿性年龄相关性黄斑变性的临床及机制研究
|
摘要
目的观察明目消朦片联合玻璃体腔注射抗血管内皮生长因子(VEGF)药物雷珠单抗治疗湿性年龄相关性黄斑变性(w AMD)的临床疗效及作用机制。方法将80例w AMD患者随机分为两组,对照组40例予雷珠单抗玻璃体腔注射治疗,治疗组40例在对照组治疗基础上加明目消朦片治疗。两组患者均每月玻璃体腔注射雷珠单抗一次,连续治疗3个月。比较两组治疗前后视力、视网膜黄斑区中心凹厚度(CMT)、血清VEGF、外周血单核细胞Toll样受体3(toll-like receptor 3,TLR3)m RNA、TLR4 mRNA的表达水平及视功能相关的生存质量量表评分变化。结果治疗后,两组视力、生存质量评分均较本组治疗前升高(P<0.05),CMT、血清VEGF水平、TLR3 mRNA、TLR4 mRNA的表达水平降低(P<0.05),且两组组间比较差异有统计学意义(P<0.05)。结论明目消朦片联合雷珠单抗玻璃体腔注射治疗有助于改善w AMD患者的视功能,降低患者CMT,其机制可能是由TLR3、TLR4介导的抗炎及抗VEGF作用。
Objective To observe the clinical efficacy and mechanism of Mingmu Xiaomeng Tablets combined with intravitreal injection of anti-vascular endothelial growth factor(VEGF) drug ranibizumab in the treatment of wet agerelated macular degeneration(wAMD). Methods Eighty patients with wAMD were randomly divided into two groups. 40 patients in the control group were treated with intravitreal injection of ranibizumab, and 40 patients in the treatment group were treated with Mingmu Xiaomeng Tablets on the basis of treatment with ranibizumab. The two groups of patients received intravitreal injection of ranibizumab once a month for 3 months. The visual acuity, central macular thickness(CMT), serum level of VEGF, expression levels of toll-like receptor 3(TLR3) mRNA and TLR4 mRNA of peripheral blood mononuclear cell, as well as visual function-related quality of life score were compared before and after treatment. Results After treatment, the visual acuity and quality of life scores of the two groups were higher than those before treatment(P<0.05), and the expression levels of CMT, serum VEGF, TLR3 mRNA and TLR4 mRNA decreased(P<0.05). The difference between the two groups was statistically significant(P<0.05). Conclusion Mingmu Xiaomeng Tablets combined with intravitreal injection of ranibizumab can improve the visual function of patients with wAMD and reduce the CMT of patients. The mechanism may be related to anti-inflammatory and anti-VEGF effects mediated by TLR3 and TLR4.
Objective To observe the clinical efficacy and mechanism of Mingmu Xiaomeng Tablets combined with intravitreal injection of anti-vascular endothelial growth factor(VEGF) drug ranibizumab in the treatment of wet agerelated macular degeneration(wAMD). Methods Eighty patients with wAMD were randomly divided into two groups. 40 patients in the control group were treated with intravitreal injection of ranibizumab, and 40 patients in the treatment group were treated with Mingmu Xiaomeng Tablets on the basis of treatment with ranibizumab. The two groups of patients received intravitreal injection of ranibizumab once a month for 3 months. The visual acuity, central macular thickness(CMT), serum level of VEGF, expression levels of toll-like receptor 3(TLR3) mRNA and TLR4 mRNA of peripheral blood mononuclear cell, as well as visual function-related quality of life score were compared before and after treatment. Results After treatment, the visual acuity and quality of life scores of the two groups were higher than those before treatment(P<0.05), and the expression levels of CMT, serum VEGF, TLR3 mRNA and TLR4 mRNA decreased(P<0.05). The difference between the two groups was statistically significant(P<0.05). Conclusion Mingmu Xiaomeng Tablets combined with intravitreal injection of ranibizumab can improve the visual function of patients with wAMD and reduce the CMT of patients. The mechanism may be related to anti-inflammatory and anti-VEGF effects mediated by TLR3 and TLR4.
引文
[1]Zhang C X,Zhang G M,Ma N,et al.Awareness of age-related macular degeneration and its risk factors among Beijing residents in China[J].Chin Med J(Engl),2017,130(2):155-159.
[2]Wong W L,Su X,Li X,et al.Global prevalence of age-related macular degeneration and disease burden projection for 2020and 2040:a systematic review and meta-analysis[J].Lancet Glob Health,2014,2(2):e106-e116.
[3]Taylor D J,Hobby A E,Binns A M,et al.How does age-related macular degeneration affect real-world visual ability and quality of life?A systematic review[J].BMJ Open,2016,6(12):e11504.
[4]张彩霞,邱波,张梅芳.消朦灵方对糖尿病大鼠视网膜新生血管的抑制作用研究[J].中药新药与临床药理,2011,(6):620-623.
[5]詹文捷,邱波,庞龙,等.益气养阴活血祛痰法对玻璃体视网膜术后疗效的临床观察[J].新中医,2011,(3):68-70.
[6]李洪霞.国际标准视力表[M].南昌:江西科学技术出版社,2010:1.
[7]Berdeaux G,Mesbah M,Bradley C.Metric properties of the MacDQoL,individualized macular-disease-specific quality of life instrument,and newly identified subscales in French,German,Italian,and American populations[J].Value Health,2011,14(1):110-120.
[8]Chou R,Dana T,Bougatsos C,et al.Screening for impaired visual acuity in older adults:updated evidence report and systematic review for the US preventive services task force[J].JAMA,2016,315(9):915-933.
[9]Zhang X,Lai T.Baseline predictors of visual acuity outcome in patients with wet age-related macular degeneration[J].Biomed Res Int,2018,2018:9640131.
[10]Kauppinen A,Paterno J J,Blasiak J,et al.Inflammation and its role in age-related macular degeneration[J].Cell Mol Life Sci,2016,73(9):1765-1786.
[11]Langmann T,Fauser S.Polysialic acid for immunomodulation in an animal model for wet age-related macular degeneration(AMD)[J].Klin Monbl Augenheilkd,2017,234(5):657-661.
[12]Alexander P,Gibson J,Cree A J,et al.Complement factor I and age-related macular degeneration[J].Mol Vis,2014,20:1253-1257.
[13]Mohan R R,Cabrera A P,Harrison R E,et al.Peptide redesign for inhibition of the complement system:Targeting age-related macular degeneration[J].Mol Vis,2016,22:1280-1290.
[14]Bora N S,Matta B,Lyzogubov V V,et al.Relationship between the complement system,risk factors and prediction models in age-related macular degeneration[J].Mol Immunol,2015,63(2):176-183.
[15]Ozaki E,Campbell M,Kiang A S,et al.Inflammation in agerelated macular degeneration[J].Adv Exp Med Biol,2014,801:229-235.
[16]Stewart E A,Wei R,Branch M J,et al.Expression of Toll-like receptors in human retinal and choroidal vascular endothelial cells[J].Exp Eye Res,2015,138:114-123.
[17]Singh P K,Kumar A.Retinal photoreceptor expresses tolllike receptors(TLRs)and elicits innate responses following TLR ligand and bacterial challenge[J].PLoS One,2015,10(3):e119541.
[18]Gao M L,Wu K C,Deng W L,et al.Toll-like receptor 3 activation initiates photoreceptor cell death In vivo and in vitro[J].Invest Ophthalmol Vis Sci,2017,58(2):801-811.
[19]Klettner A,Hamann T,Schluter K,et al.Retinal pigment epithelium cells alter the pro-inflammatory response of retinal microglia to TLR-3 stimulation[J].Acta Ophthalmol,2014,92(8):e621-e629.
[20]Mai K,Chui J J,Di Girolamo N,et al.Role of toll-like receptors in human iris pigment epithelial cells and their response to pathogenassociated molecular patterns[J].J Inflamm(Lond),2014,11:20.
[21]Kleinman M E,Yamada K,Takeda A,et al.Sequence-and targetindependent angiogenesis suppression by siRNA via TLR3[J].Nature,2008,452(7187):591-597.
[22]Ryoo N K,Lee J,Lee H,et al.Therapeutic effects of a novel siRNA-based anti-VEGF(siVEGF)nanoball for the treatment of choroidal neovascularization[J].Nanoscale,2017,9(40):15461-15469.
[23]Chen L,Bai Y,Zhao M,et al.TLR4 inhibitor attenuates amyloidbeta-induced angiogenic and inflammatory factors in ARPE-19cells:Implications for age-related macular degeneration[J].Mol Med Rep,2016,13(4):3249-3256.
[24]Mitchell J,Bradley C.Quality of life in age-related macular degeneration:a review of the literature[J].Health Qual Life Outcomes,2006,4:97.
[2]Wong W L,Su X,Li X,et al.Global prevalence of age-related macular degeneration and disease burden projection for 2020and 2040:a systematic review and meta-analysis[J].Lancet Glob Health,2014,2(2):e106-e116.
[3]Taylor D J,Hobby A E,Binns A M,et al.How does age-related macular degeneration affect real-world visual ability and quality of life?A systematic review[J].BMJ Open,2016,6(12):e11504.
[4]张彩霞,邱波,张梅芳.消朦灵方对糖尿病大鼠视网膜新生血管的抑制作用研究[J].中药新药与临床药理,2011,(6):620-623.
[5]詹文捷,邱波,庞龙,等.益气养阴活血祛痰法对玻璃体视网膜术后疗效的临床观察[J].新中医,2011,(3):68-70.
[6]李洪霞.国际标准视力表[M].南昌:江西科学技术出版社,2010:1.
[7]Berdeaux G,Mesbah M,Bradley C.Metric properties of the MacDQoL,individualized macular-disease-specific quality of life instrument,and newly identified subscales in French,German,Italian,and American populations[J].Value Health,2011,14(1):110-120.
[8]Chou R,Dana T,Bougatsos C,et al.Screening for impaired visual acuity in older adults:updated evidence report and systematic review for the US preventive services task force[J].JAMA,2016,315(9):915-933.
[9]Zhang X,Lai T.Baseline predictors of visual acuity outcome in patients with wet age-related macular degeneration[J].Biomed Res Int,2018,2018:9640131.
[10]Kauppinen A,Paterno J J,Blasiak J,et al.Inflammation and its role in age-related macular degeneration[J].Cell Mol Life Sci,2016,73(9):1765-1786.
[11]Langmann T,Fauser S.Polysialic acid for immunomodulation in an animal model for wet age-related macular degeneration(AMD)[J].Klin Monbl Augenheilkd,2017,234(5):657-661.
[12]Alexander P,Gibson J,Cree A J,et al.Complement factor I and age-related macular degeneration[J].Mol Vis,2014,20:1253-1257.
[13]Mohan R R,Cabrera A P,Harrison R E,et al.Peptide redesign for inhibition of the complement system:Targeting age-related macular degeneration[J].Mol Vis,2016,22:1280-1290.
[14]Bora N S,Matta B,Lyzogubov V V,et al.Relationship between the complement system,risk factors and prediction models in age-related macular degeneration[J].Mol Immunol,2015,63(2):176-183.
[15]Ozaki E,Campbell M,Kiang A S,et al.Inflammation in agerelated macular degeneration[J].Adv Exp Med Biol,2014,801:229-235.
[16]Stewart E A,Wei R,Branch M J,et al.Expression of Toll-like receptors in human retinal and choroidal vascular endothelial cells[J].Exp Eye Res,2015,138:114-123.
[17]Singh P K,Kumar A.Retinal photoreceptor expresses tolllike receptors(TLRs)and elicits innate responses following TLR ligand and bacterial challenge[J].PLoS One,2015,10(3):e119541.
[18]Gao M L,Wu K C,Deng W L,et al.Toll-like receptor 3 activation initiates photoreceptor cell death In vivo and in vitro[J].Invest Ophthalmol Vis Sci,2017,58(2):801-811.
[19]Klettner A,Hamann T,Schluter K,et al.Retinal pigment epithelium cells alter the pro-inflammatory response of retinal microglia to TLR-3 stimulation[J].Acta Ophthalmol,2014,92(8):e621-e629.
[20]Mai K,Chui J J,Di Girolamo N,et al.Role of toll-like receptors in human iris pigment epithelial cells and their response to pathogenassociated molecular patterns[J].J Inflamm(Lond),2014,11:20.
[21]Kleinman M E,Yamada K,Takeda A,et al.Sequence-and targetindependent angiogenesis suppression by siRNA via TLR3[J].Nature,2008,452(7187):591-597.
[22]Ryoo N K,Lee J,Lee H,et al.Therapeutic effects of a novel siRNA-based anti-VEGF(siVEGF)nanoball for the treatment of choroidal neovascularization[J].Nanoscale,2017,9(40):15461-15469.
[23]Chen L,Bai Y,Zhao M,et al.TLR4 inhibitor attenuates amyloidbeta-induced angiogenic and inflammatory factors in ARPE-19cells:Implications for age-related macular degeneration[J].Mol Med Rep,2016,13(4):3249-3256.
[24]Mitchell J,Bradley C.Quality of life in age-related macular degeneration:a review of the literature[J].Health Qual Life Outcomes,2006,4:97.