儿童特发性矮小症rhGH治疗前后血清SMAD3、miR-189水平检测及对预后评估价值

Measurement of serum SMAD3 and miR-189 levels before and after rhGH treatment in children with idiopathic short stature and their value in prognosis evaluation

目的探究儿童特发性矮小症(ISS)重组人生长激素(rhGH)治疗前后血清Smad同源物3(SMAD3)、微小RNA(miR)-189水平,并分析其对预后的评估价值,为临床治疗提供参考。方法选取2021年2月至2022年5月收治的136例ISS患儿为观察组,均接受rhGH治疗,另选取同期136例健康儿童为对照组,比较两组血清SMAD3、miR-189水平,比较ISS患儿rhGH治疗前后血清SMAD3、miR-189水平、骨龄指标[骨龄指数(BAI)、骨龄年龄差(BAD)]及体格指标[身高、体质量、体质量指数(BMI)]。根据治疗12个月后预后分为预后良好组、预后不良组,比较不同预后ISS患儿血清SMAD3、miR-189水平,分析对ISS患儿预后的评估价值。结果观察组miR-189水平高于对照组,SMAD3水平低于对照组(P<0.05);ISS患儿rhGH治疗3、6个月后血清SMAD3水平、BAI、BAD、身高、体质量、BMI较治疗前升高,血清miR-189水平较治疗前降低(P<0.05);ISS患儿BAI、BAD、身高、体质量、BMI与血清SMAD3呈正相关,与miR-189呈负相关(P<0.05);在ISS患儿预后不良中,SMAD3低表达与miR-189高表达呈正向交互作用,为次相乘模型;预后良好组治疗前、治疗3个月、治疗6个月血清SMAD3水平高于预后不良组,miR-189水平低于预后不良组(P<0.05),治疗前、治疗3个月、治疗6个月SMAD3、miR-189联合评估的AUC分别为0.879、0.907、0.938(P<0.05),评估效能较高。结论ISS患儿血清SMAD3、miR-189水平存在异常改变,与骨龄、体格有关,miR-189高表达与SMAD3低表达在预后不良中有正向交互作用,早期检测血清SMAD3、miR-189可作为评估rhGH治疗预后的有效指标,为后续治疗提供参考依据。

Objective To explore the changes in serum levels of Smad homolog 3(SMAD3)and microRNA(miR)-189 before and after recombinant human growth hormone(rhGH)treatment in children with idiopathic short stature(ISS),and analyze their prognostic value,providing a reference for clinical treatment.Methods A total of 136 children with ISS from February 2021 to May 2022 were selected as the observation group,all receiving rhGH treatment,and 136 healthy children were selected as the control group during the same period.Serum SMAD3 and miR-189 levels were compared between the two groups.The serum levels of SMAD3,miR-189,bone age indexes[bone age index(BAI),bone age difference(BAD)]and physical indexes[height,weight,body mass index(BMI)]of ISS children were compared before and after rhGH treatment.According to the prognosis after 12 months of treatment,they were divided into good prognosis group and poor prognosis group.Serum SMAD3 and miR-189 levels of ISS children with different prognosis were compared to analyze the evaluation value of ISS children with different prognosis.Results The level of miR-189 in the observation group was higher than that in the control group,while the level of SMAD3 was lower than that in the control group(P<0.05).After 3 and 6 months of rhGH treatment,compared with before treatment,the serum SMAD3 level,BAI,BAD,height,weight,and BMI in children with ISS were increased,while the serum miR-189 level was decreased(P<0.05).In children with ISS,BAI,BAD,height,weight,and BMI were positively correlated with serum SMAD3,while negatively correlated with miR-189(P<0.05).In the poor prognosis of children with ISS,the low expression of SMAD3 and the high expression of miR-189 interact positively,forming a secondary multiplicative model.The serum SMAD3 level in the good prognosis group was higher than that in the poor prognosis group before treatment and at 3 and 6 months after treatment,while the miR-189 level was lower than that in the poor prognosis group (P<0.05). The AUC of SMAD3 and miR-189 combined assessment before treatment, at 3 and 6 months aftertreatment were 0.879, 0.907, and 0.938, respectively (P<0.05), indicating high assessment efficiency. Conclusion The abnormalchanges in serum SMAD3 and miR-189 levels in children with ISS are related to bone age and physical fitness. The high expressionof miR-189 and low expression of SMAD3 have a positive interaction in poor prognosis. Early detection of serumSMAD3 and miR-189 can be used as an effective indicator for evaluating the prognosis of rhGH treatment, providing a referencefor subsequent treatment.