摘要
目的 探讨雷珠单抗联合激光光凝对早产儿视网膜病变(ROP)的疗效及血管紧张素Ⅱ(AngⅡ)介导的转化生长因子-β(TGF-β)/Smad同源物4(Smad4)信号通路机制。方法 选取2022年2月至2024年2月武汉市普仁医院眼科收治的92例ROP患儿为研究对象。根据治疗方法不同分为联合组(n=46眼)与对照组(n=46眼)。联合组采用注射雷珠单抗联合810 nm激光光凝治疗;对照组采用810 nm激光光凝治疗。评估患儿视力、视野、眼底结构、不良反应事件及可能信号通路机制TGF-β/Smad4等指标。通过培养患儿外周血单核细胞(PBMCs),观察血管紧张素Ⅱ(AngⅡ)和雷珠单抗对TGF-β/Smad4信号通路的影响。结果 治疗前后两组患儿的视力(F=6.82,P=0.002)、视野(F=8.15,P=0.001)、视网膜血管化时间(F=18.35,P<0.05)和嵴消退时间(F=5.83,P<0.05)均存在显著的交互作用。治疗后1个月、3个月两组患儿视力均高于本组治疗前(均P<0.01)。治疗后1个月、3个月,联合组视力均高于对照组[1个月:(0.35±0.12)vs(0.25±0.10);3个月:(0.45±0.15)vs(0.32±0.11)](P<0.01)。治疗后1个月、3个月两组患儿视野均高于本组治疗前(P<0.01)。治疗后1个月、3个月,联合治疗组视野均高于对照组[1个月:(80.34±12.67)°vs(70.45±11.89)°;3个月:(85.67±13.25)°vs(75.23±12.45)°](均P<0.01)。治疗后1个月、3个月,联合治疗组眼底结构改善情况优于对照组(均P<0.05)。治疗后1个月、3个月,两组TGF-β mRNA、Smad4 mRNA各指标均低于同组治疗前(均P<0.05),且联合组TGF-β mRNA、Smad4 mRNA各指标均低于对照组(均P<0.05)。两组不良反应发生率均较低,差异无统计学意义(χ^(2)=1.046,P=0.307)。细胞实验结果表明,与对照组相比,不同浓度的AngⅡ均能促进ROP患儿PBMC中TGF-β mRNA和Smad4 mRNA的水平升高(均P<0.05),加入雷珠单抗后能有效降低AngⅡ所致TGF-β mRNA和Smad4 mRNA水平的升高(P<0.05)。结论 雷珠单抗联合激光治疗ROP在提升患儿视力、扩大视野、改善眼底结构以及调控抑制TGF-β/Smad4通路活性方面均表现出显著优势。
Objective To explore the effect of ranibizumab combined with laser photocoagulation on treatment of retinopathy of prematurity(ROP)and AngⅡ-mediated transforming growth factor-β(TGF-β)/smad homolog 4(Smad4)pathway mechanisms.Methods A total of 92 children who were diagnosed with ROP and admitted to the Ophthalmology Department of Wuhan Puren Hospital from February 2022 to February 2024 were enrolled as the research subjects.According to the general information matching principles,the children were categorized into the combination group(n=46 eyes)and the control group(n=46 eyes).The combination group received intravitreal injection of ranibizumab in conjunction with 810 nm laser photocoagulation,whereas the control group only received laser treatment.The parameters such as visual acuity,visual field,fundus structure,occurrence of adverse events,and the TGF-β/Smad4 signaling pathway mechanisms were evaluated.Results There were significant interactions of the visual acuity(F=6.82,P=0.002),visual field(F=8.15,P=0.001),retinal vascularization time(F=18.35,P<0.05),and ridge regression time(F=5.83,P<0.05)of the two groups before and after treatment.The visual acuity of both groups was higher after the treatment for 1 and 3 months than before the treatment(all P<0.01).The visual acuity of the combination group((0.35±0.12),(0.45±0.15))was higher than that of the control group((0.25±0.10),(0.32±0.11))(both P<0.01).The visual fields of both groups were higher after the treatment for 1 and 3 months than before the treatment(all P<0.01).The visual fields of the combination group were higher than those of the control group after the treatment for 1 and 3 months((80.34±12.67)°vs(70.45±11.89)°,(85.67±13.25)°vs(75.23±12.45)°)(both P<0.01).The improvement in fundus structure of the combined group was better than that of the control group after the treatment for 1 and 3 months(all P<0.05).Regarding the TGF-β/Smad4 pathway,the levels of TGF-βmRNA and Smad4 mRNA in both groups were lower after the treatment than before the treatment(both P<0.05),and the levels of the above indexes of the combination group were lower than those of the control group(both P<0.05).The incidence rates of adverse reactions were relatively low in the two groups,and there were no significant differences between the two groups(χ^(2)=1.046,P=0.307).The cell experiment results showed that compared with the control group,different concentrations of AngⅡcould promote the increase of TGF-βmRNA and Smad4 mRNA levels in PBMCs of ROP children(both P<0.05),and the addition of ranibizumab could effectively reduce the increase of TGF-βmRNA and Smad4 mRNA levels caused by AngⅡ(P<0.05).Conclusion The combination of ranibizumab and laser treatment for ROP demonstrates remarkable advantages in enhancing visual acuity,enlarging visual fields,improving fundus structure,and modulating and inhibiting the activity of the TGF-β/Smad4 pathway.
作者
魏谭伟
刘志平
彭建军
Wei Tanwei;Liu Zhiping;Peng Jianjun(Department of Ophthalmology,Wuhan Puren Hospital,Wuhan 430080,China;Department of Cardiovascular Medicine,the Central Hospital of Wuhan,Wuhan 430014,China)
出处
《中国药物应用与监测》
2025年第4期681-686,共6页
Chinese Journal of Drug Application and Monitoring
基金
湖北省医学科研项目(2021W356)
武汉市卫健委科研项目(WX20Z25)。
