乌司他丁通过抑制Wnt/β-Catenin信号通路活性减轻糖尿病大鼠神经病变性疼痛  

Effect of Ulinastatin on Neurodegenerative Pain in Diabetic Rats by Inhibiting the Activity of Wnt/Β-Catenin Signaling Pathway

作　　者：周丹[1] 李文 赵曦[1] Zhou Dan;Li Wen;Zhao Xi(Department of Anesthesiology,Department of Stomatology,People′s Hospital of Deyang City,Deyang,Sichuan 618000,China)

机构地区：[1]德阳市人民医院麻醉科,口腔科,德阳618000

出　　处：《四川医学》2022年第4期327-332,共6页Sichuan Medical Journal

基　　金：德阳市科技计划项目(编号:2020SZZ095)。

摘　　要：目的探讨乌司他丁减轻糖尿病大鼠神经病变性疼痛(DNP)的效应及相关信号通路。方法将36只SD大鼠随机分为对照组(Con组)、DNP模型组(DNP组)、乌司他丁治疗组(ULI组),分别采取不同的干预措施。对大鼠进行机械缩足反射阈值(MWT)测试和热缩足反射潜伏期(TWL)测试。分批处死大鼠,解剖分离L3~5脊髓,采用Western Blot检测Wnt 10a蛋白、β-catenin蛋白的表达水平。采用ELISA法检测瘤坏死因子-α(TNF-α)和白细胞介素-1(IL-1)等炎性因子的表达水平。结果①DNP组各时间点的MWT和TWL值均显著低于Con组。与Con组相比,ULI组的WMT值及TWL值更高(P<0.05)。Western Blot检测显示,与Con组相比,DNP组大鼠脊髓Wnt 10a蛋白和β-catenin蛋白的表达水平增加(P<0.05),ULI组Wnt 10a和β-catenin蛋白表达水平显著降低(P<0.05)。②与Con组相比,DNP组脊髓星形胶质细胞明显激活,Wnt 10a和β-catenin表达增强。ULI组星形胶质细胞的激活受到抑制,Wnt 10a和β-catenin的表达也受到抑制。③ELISA检测显示,在注射链脲佐菌素后第39、42、45天,由Wnt 10a/β-catenin信号通路激活的TNF-α和IL-1β水平显著升高,经乌司他丁干预后,显著降低了TNF-α和IL-1β水平。结论乌司他丁可通过抑制炎症和星形胶质细胞的激活减轻大鼠DNP症状,这可能是通过Wnt 10a/β-catenin信号通路实现的。Objective To investigate the effect of ulinastatin in reducing DNP of diabetic rats and the related signal pathway.Methods 36 rats were randomly divided into control group,DNP group and Uli group.MWT test and TWL test were performed on rats.The expression levels of Wnt 10a andβ-Catenin were detected in L3~5 spinal cord.The expression levels of TNF-αand IL-1 were detected.Results①MWT and TWL in DNP group were significantly lower than those in control group.Compared with control group,the WMT and TWL of Uli group were higher(P<0.05).Compared with control group,the expression levels of Wnt 10a andβ-Catenin in spinal cord of DNP group were significantly increased(P<0.05),while Wnt 10a andβ-Catenin protein levels in Uli group were significantly decreased(P<0.05).②Compared with control group,the expression of Wnt 10a andβ-Catenin increased in DNP group.The activation of astrocytes and the expression of Wnt 10a andβ-Catenin were inhibited in Uli group.③ELISA showed that the levels of TNF-αand IL-1βactivated by Wnt 10a/β-catenin signaling pathway were significantly increased on the 39th,42nd and 45th days after STZ injection.After Ulinastatin intervention,the levels of TNF-αand IL-1βwere significantly decreased.Conclusion Ulinastatin can reduce DNP symptoms by inhibiting inflammation and activation of astrocytes,which may be achieved through Wnt 10a/β-catenin signaling pathway.

关 键 词：乌司他丁 糖尿病 神经病变性疼痛 

分 类 号：R-332[医药卫生]