Cheng Jiangxia, He Yuxin, Wang Zhuo, Wang Zhengchao, Peng Xiaohong, Zhang Liangcheng
Department of Anesthesia, Fujian Medical University Union Hospital, Fuzhou, China.
Department of Anesthesia, Wuhan Fourth Hospital, Wuhan, China.
J Cell Mol Med. 2025 Jan;29(2):e70311. doi: 10.1111/jcmm.70311.
In this study, we aimed to explore the sex-specific effects and mechanisms of sevoflurane exposure on the neural development of pubertal rats on the basis of M1/M2 microglial cell polarisation and related signalling pathways. A total of 48 rat pups (24 males and 24 females) were assigned to the 0- or 2-h sevoflurane exposure group on the seventh day after birth. The Morris water maze (MWM) test was subsequently conducted on the 32nd to 38th days after birth. M1/M2 microglial cell polarisation, C3 and TLR4 expression, and synapse growth were analysed within specific brain zones by immunofluorescence after the MWM test. We found that the negative effects caused by sevoflurane exposure were weaker in female rats than in male rats and had less influence on spatial memory. Sevoflurane exposure has opposite effects on microglial M1 polarisation in the different sexes but can promote M2 polarisation, with more obvious effects seen in female rats. In addition, sevoflurane exposure had bidirectional effects on C3 expression in different zones, while it clearly downregulated C3 expression in female rats. Moreover, sevoflurane decreased TLR4 expression in the hippocampus, whereas female rats exhibited better resistance, especially in the dentate gyrus. Compared with male rats, female rats were more resistant to the synaptic reduction effect of sevoflurane exposure. In conclusion, we found that neonatal sevoflurane exposure could exhibit sex-specific effects via the regulation of C3- and TLR4-related microglial cell polarisation. In addition, subregional regulation in the hippocampus might also contribute to its sex-specific effects.
在本研究中，我们旨在基于M1/M2小胶质细胞极化及相关信号通路，探讨七氟醚暴露对青春期大鼠神经发育的性别特异性影响及机制。将48只新生大鼠幼崽（24只雄性和24只雌性）在出生后第7天分为0小时或2小时七氟醚暴露组。随后在出生后第32至38天进行莫里斯水迷宫（MWM）试验。在MWM试验后，通过免疫荧光分析特定脑区的M1/M2小胶质细胞极化、C3和TLR4表达以及突触生长情况。我们发现，七氟醚暴露对雌性大鼠造成的负面影响弱于雄性大鼠，对空间记忆的影响也较小。七氟醚暴露对不同性别的小胶质细胞M1极化有相反的影响，但可促进M2极化，在雌性大鼠中更为明显。此外，七氟醚暴露对不同脑区的C3表达有双向影响，而在雌性大鼠中明显下调C3表达。而且，七氟醚降低海马体中的TLR4表达，而雌性大鼠表现出更好的抵抗力，尤其是在齿状回。与雄性大鼠相比，雌性大鼠对七氟醚暴露引起的突触减少效应更具抵抗力。总之，我们发现新生期七氟醚暴露可通过调节与C3和TLR4相关的小胶质细胞极化表现出性别特异性影响。此外，海马体中的亚区域调节也可能导致其性别特异性影响。
