抑制Wnt/β-catenin信号通路对大鼠蛛网膜下腔出血后软脑膜纤维化影响的研究  

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

作　　者：张贵强[1] 许文锋 邹昂儒[1] Zhang Guiqiang;Xu Wenfeng;Zou Angru(Department of Neurology,Guangxi Zhuang Autonomous Region Nationality Hospital,Nanning,Guangxi,530001,China)

机构地区：[1]广西壮族自治区民族医院神经内科,广西南宁530001 [2]广西壮族自治区工人医院神经内科,广西南宁530022

出　　处：《黑龙江医学》2025年第5期553-555,共3页Heilongjiang Medical Journal

基　　金：广西壮族自治区卫生健康委员会自筹经费科研项目(Z20190542)。

摘　　要：目的:明确Wnt/β-catenin通路阻滞剂DKK-1对大鼠蛛网膜下腔出血(SAH)后软脑膜纤维化表达的影响。方法:选取SD大鼠72只,按随机数表法分为假手术组、SAH模型组和DKK-1抑制剂组,每组各24只。采用ELISA法检测相应时间点(术后第7 d、14 d和28 d)的各组大鼠脑脊液中转化生长因子-β1(TGF-β1)浓度及I型前胶原前肽(PICP)的浓度,并取脑组织行Masson染色,观察软脑膜的纤维化程度。结果:SAH模型组大鼠脑脊液中的TGF-β1在术后第7 d开始上升,第14 d下降,第28 d再次显著上升,呈双峰相波形。DKK-1抑制剂组大鼠脑脊液中的TGF-β1浓度在不同时间段均明显低于SAH模型组,差异均有统计学意义(t=0.45、0.25、1.82,P<0.05);SAH模型组大鼠脑脊液中的PICP浓度在第7 d开始升高,第14 d达到高峰显著升高并持续到第28 d,DKK-1抑制剂组大鼠脑脊液中的PICP浓度显著低于SAH模型组,差异均有统计学意义(t=1.25、7.16、7.68,P<0.05);术后第28 d,DKK-1抑制剂组大鼠软脑膜的灰度值显著高于SAH模型组及假手术组,厚度、胶原纤维含量显著低于SAH模型组及假手术组,差异均有统计学意义(t=4.82、7.68、7.16,P<0.05);PICP浓度与软脑膜的胶原纤维衡量指标显著正相关(r=0.651,P<0.05)。结论:SAH后脑脊液中PICP和TGF-β1浓度增高,引起软脑膜纤维化。DKK-1抑制剂可通过抑制Wnt/β-catenin信号通路降低SAH脑脊液PICP和TGF-β1水平,改善SAH大鼠脑组织纤维化,提示阻断Wnt/β-catenin信号通路可能成为治疗SAH后软脑膜纤维化的新手段。Objective:To investigate the effect of Wnt/β-catenin pathway blocker DKK-l on the expression of TGF-Β1 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=0.651,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 le

关 键 词：蛛网膜下腔出血 Wnt/β-catenin通路阻滞剂DKK-1 转化生长因子-β1 I型前胶原前肽 

分 类 号：R741[医药卫生—神经病学与精神病学]