Lin Lin, Li Siyuan, Liu Que, Zhang Xingxing, Xiong Ying, Zhao Shaoyun, Cao Liyue, Gong Jiaxuan, Liu Yaping, Wu Rong
Department of Traditional Chinese Medicine, Shijiazhuang Medical College, Shijiazhuang, Hebei, China.
College of Acupuncture Moxibustion and Tuina, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
Front Microbiol. 2025 Jan 3;15:1492783. doi: 10.3389/fmicb.2024.1492783. eCollection 2024.
This study aimed to investigate the potential relation between the retarded growth of skeletal muscle (SM) and dysbiosis of gut microbiota (GM) in children with asthma, and to explore the potential action mechanisms of traditional pediatric massage (TPM) from the perspective of regulating GM and short-chain fatty acids (SCFAs) production by using an adolescent rat model of asthma.
Male Sprague-Dawley rats aged 3weeks were divided randomly into the 5 groups (n=6~7) of control, ovalbumin (OVA), OVA + TPM, OVA + methylprednisolone sodium succinate (MP) and OVA + SCFAs. Pulmonary function (PF) was detected by whole body plethysmograph, including enhanced pause and minute ventilation. Airway allergic inflammation (AAI) status was assessed by concentrations of OVA-specific immunoglobulin E in plasma, interleukin (IL)-4 and IL-1β in bronchoalveolar lavage fluid via ELISA assay. SM mass was assessed by using cross-sectional areas of diaphragm muscle and gastrocnemius via hematoxylin and eosin staining. GM and SCFAs production were detected by 16S rDNA sequencing and GC-MS, respectively. The protein and gene expressions of free fatty acid receptor 2 in SM were detected by using immunohistochemical staining and qRT-PCR, respectively. qRT-PCR was used to detect other relative gene expressions that were closely related with SM mass. The activity of insulin-like growth factor-1 (IGF-1)/protein kinase B (PKB/AKT) pathway in SM was detected by western blotting test.
OVA exposure caused obvious AAI and poor PF in adolescent rats. OVA-exposed adolescent rats had a retarded growth of SM mass and inhibited activity of IGF-1/AKT pathway, which was related with GM dysbiosis, reduced SCFAs production and FFAR2 expressions in SM. TPM efficiently enhanced the SM mass, along with alleviating AAI and improving PF. TPM activated IGF-1/AKT pathway in SM, which was closely related with correcting GM dysbiosis, enhanced SCFAs production and FFAR2 expressions.
The retarded growth of SM mass and inhibition of IGF-1/AKT pathway existed in OVA-exposed adolescent rats, which was related with GM dysbiosis, reduced SCFAs production and FFAR2 expressions in SM. TPM efficiently enhanced the SM mass, at least, partially via regulating GM, enhancing SCFAs production and activating FFAR2-IGF-1/AKT pathway.
本研究旨在探讨哮喘患儿骨骼肌（SM）生长迟缓与肠道微生物群（GM）失调之间的潜在关系，并通过青少年哮喘大鼠模型，从调节GM和短链脂肪酸（SCFAs）产生的角度探索传统小儿推拿（TPM）的潜在作用机制。
将3周龄雄性Sprague-Dawley大鼠随机分为5组（n = 6~7），即对照组、卵清蛋白（OVA）组、OVA + TPM组、OVA + 琥珀酸甲泼尼龙（MP）组和OVA + SCFAs组。采用全身容积描记法检测肺功能（PF），包括增强间歇和分钟通气量。通过ELISA法检测血浆中OVA特异性免疫球蛋白E、支气管肺泡灌洗液中白细胞介素（IL）-4和IL-1β的浓度，评估气道过敏性炎症（AAI）状态。通过苏木精-伊红染色，利用膈肌和腓肠肌的横截面积评估SM质量。分别采用16S rDNA测序和GC-MS检测GM和SCFAs的产生。分别采用免疫组织化学染色和qRT-PCR检测SM中游离脂肪酸受体2的蛋白和基因表达。采用qRT-PCR检测与SM质量密切相关的其他相关基因表达。通过蛋白质印迹试验检测SM中胰岛素样生长因子-1（IGF-1）/蛋白激酶B（PKB/AKT）信号通路的活性。
OVA暴露导致青少年大鼠出现明显的AAI和较差的PF。暴露于OVA的青少年大鼠SM质量生长迟缓，IGF-1/AKT信号通路活性受到抑制，这与GM失调、SCFAs产生减少以及SM中FFAR2表达降低有关。TPM有效增加了SM质量，同时减轻了AAI并改善了PF。TPM激活了SM中的IGF-1/AKT信号通路，这与纠正GM失调、增加SCFAs产生以及FFAR2表达密切相关。
暴露于OVA的青少年大鼠存在SM质量生长迟缓和IGF-1/AKT信号通路抑制的情况，这与GM失调、SCFAs产生减少以及SM中FFAR2表达降低有关。TPM至少部分通过调节GM、增加SCFAs产生以及激活FFAR2-IGF-1/AKT信号通路有效增加了SM质量。
