Effects of Inhibition of Wnt/β-catenin Signaling Pathway on Subarachnoid Hemorrhage Leptomeningeal Fibrosis in Rats

Zhang Guiqiang; Xu Wenfeng; Zou Angru

doi:10.3969/j.issn.1004-5775.2025.05.011

Abstract：Objective:To investigate the effect of Wnt/β-catenin pathway blocker DKK-l on the expression of TGF-B1 in subarachnoid hemorrhage leptomeningeal fibrosis in rats.Methods:72 SD rats were randomly divided into Sham Operation Group,SAH Model Group and DKK-1 inhibitor group,with 24 rats in each group.The concentrations of TGF-β1 and Procollagen Type Ⅰ(PICP)in cerebrospinal fluid(CSF)were measured by ELISA at the corresponding time points(7th,14th and 28th days after Operation),the degree of pial fibrosis was observed.Results:The level of TGF-β1 in CSF of SAH Model Group began to increase on the 7th day after operation,decreased on the 14th day after operation,and increased again on the 28th day.The concentration of TGF-β1 in CSF of DKK-1 inhibitor group was significantly lower than that of SAH model group at different time points(t=0.45,0.25,1.82;P＜0.05).The PICP concentration in CSF of SAH Model Group began to increase on the 7th day,reached the peak on the 14th day and lasted to the 28th day.The PICP concentration in CSF of DKK-1 inhibitor group was significantly lower than that of SAH Model Group(t=1.25,7.16,7.68;P＜0.05).On the 28th day after operation,the gray value of pial meninges in DKK-1 inhibitor group was significantly higher than that in SAH Model Group and Sham Operation Group,and the thickness of pial meninges in DKK-1 inhibitor group was significantly lower than that in SAH Model Group and Sham Operation Group,with statistically significant difference(t=4.82,7.68,7.16;P＜0.05).The PICP concentration was positively correlated with the measurement of collagen fibers in pial meninges(r=0.65 1,P＜0.05).Conclusion:The level of PICP and TGF-β1 in cerebrospinal fluid were increased after SAH,resulting in leptomeningeal fibrosis.DKK-1 inhibitors can reduce PICP and TGF-β1 levels in SAH cerebrospinal fluid by inhibiting Wnt/β-catenin signaling pathway,and improve brain tissue fibrosis in SAH rats,suggesting that blocking Wnt/β-catenin signaling pathway may be a new means to treat subarachnoid hemorrhage leptomeningeal fibrosis.