基于miR-874-3p/SMAD3信号通路分析来曲唑联合生长激素治疗大骨龄矮小症患者的作用机制  

Analysis of mechanism of treating short stature with large bone age by letrozole combined with growth hormone based on miR-874-3p/SMAD3 axis

作　　者：潘杰 王柱军 张亚军 Pan Jie;Wang Zhu-jun;Zhang Ya-jun(Department of Pediatrics,Wuhan Eighth Hospital,Wuhan 430223,China;Department of Pediatrics,Tongji Medical College Affiliated Union Hospital,Huazhong University of Science and Technology,Wuhan 430022,China)

机构地区：[1]武汉市第八医院儿科,武汉430223 [2]华中科技大学同济医学院附属协和医院儿科,武汉430022

出　　处：《中国药物应用与监测》2025年第1期174-178,共5页Chinese Journal of Drug Application and Monitoring

基　　金：湖北省自然科学基金项目(2024AFB644)。

摘　　要：目的探讨基于miR-874-3p/SMAD3信号通路分析来曲唑联合生长激素治疗大骨龄矮小症的作用机制。方法回顾性分析武汉市第八医院儿科2021年1月至2024年2月收治的80例大骨龄矮小症的病历资料,均为男童,根据治疗方法的差异分为研究组(n=41)和对照组(n=39),对照组给予生长激素治疗,研究组在对照组的基础上联合来曲唑治疗。比较两组患儿治疗前后的骨代谢指标[血清骨钙素、骨碱性磷酸酶、β-胶原降解产物(β-CTX)]、生长指标(身高、骨龄、生长速度)、血糖指标(血糖、糖化血红蛋白)、血清胰岛素样生长因子1、胰岛素样生长因子结合蛋白3水平及miR-874-3p/SMAD3信号通路相关mRNA,并统计两组不良反应发生情况。结果研究组治疗后的身高、骨龄、生长速度、骨钙素、骨碱性磷酸酶、胰岛素样生长因子1、胰岛素样生长因子结合蛋白3水平、miR-874-3pmRNA、SMAD3 mRNA、β-CTX[分别为(122.70±2.62)cm、(8.52±0.33)岁、(9.13±2.06)cm·年^(-1)、(85.96±13.09)μg·L^(-1)、(172.98±39.20)μg·L^(-1)、(168.52±15.06)ng·mL^(-1)、(6.87±0.72)μg·mL^(-1)、(1.63±0.21)、(1.85±0.30)、(0.43±0.10)μg·L^(-1)]均优于对照组[分别为(117.09±7.13)cm、(8.12±0.76)岁、(7.16±1.85)cm·年^(-1)、(72.09±12.51)μg·L^(-1)、(131.09±35.02)μg·L^(-1)、(151.08±13.96)ng·mL^(-1)、(6.15±0.60)μg·mL^(-1)、(1.30±0.23)、(1.53±0.36)、(0.62±0.16)μg·L^(-1)](t=4.716、3.079、4.492、4.840、5.031、5.365、4.846、6.707、4.328、6.403,均P<0.05)。两组患儿血糖、糖化血红蛋白以及不良反应发生率比较差异无统计学意义(P>0.05)。结论来曲唑联合生长激素可有效改善大骨龄矮小男童骨代谢和胰岛素样生长因子1、胰岛素样生长因子结合蛋白3水平,促进患儿生长发育,可能与调节miR-874-3p/SMAD3信号通路有关。Objective To investigate the mechanism of letrozole combined with growth hormone in the treatment of short stature boys with large bone age based on miR-874-3p/SMAD3 axis.Methods A retrospective analysis was performed on 80 short stature boys with large bone age admitted to Wuhan Eighth Hospital from January 2021 to February 2024.According to the difference in treatment methods,they were divided into the study group(n=41)and control group(n=39).The patients in the control group were treated with growth hormone while those in the study group with letrozole on the basis of the regimen in the control group.The levels of bone metabolism indexes(serum osteocalcin,bone alkaline phosphatase,β-collagen degradation products(β-CTX)),growth indexes(height,bone age,growth rate),blood glucose indexes(blood glucose,glycosylated hemoglobin),serum insulin-like growth factor 1,insulin-like growth factor binding protein 3 and miR-874-3p/SMAD3 axis-related mRNA were compared between the two groups before and after treatment.The incidence of adverse reactions was also compared between the two groups.Results In the study group,the levels of height,bone age,growth rate,osteocalcin,bone alkaline phosphatase,insulin-like growth factor 1,insulin-like growth factor binding protein 3,miR-874-3pmRNA,SMAD3 mRNA andβ-CTX after treatment were(122.70±2.62)cm,(8.52±0.33)years old,(9.13±2.06)cm·year^(-1),(85.96±13.09)μg·L^(-1),(172.98±39.20)μg·L^(-1),(168.52±15.06)ng·mL^(-1),(6.87±0)72μg·mL^(-1),(1.63±0.21),(1.85±0.30),(0.43±0.10)μg·L^(-1),respectively.In the control group,they were(117.09±7.13)cm,(8.12±0.76)years old,(7.16±1.85)cm·year^(-1),(72.09±12.51)μg·L^(-1),(131.09±35.02)μg·L^(-1),(151.08±13.96)ng·mL^(-1),(6.15±0.60)μg·mL^(-1),(1.30±0.23),(1.53±0.36),(0.62±0.16)μg·L^(-1),respectively.They were significantly higher in the study group than in the control(t=4.716,3.079,4.492,4.840,5.031,5.365,4.846,6.707,4.328,6.403,all P<0.05).There were no significant differences in levels of blood glucose and glyc

关 键 词：miR-874-3p/SMAD3信号通路 来曲唑 生长激素 大骨龄矮小症 生长发育 

分 类 号：R969[医药卫生—药理学]