刺山柑总生物碱对系统性硬皮病小鼠Wnt3a/β-catenin 表达的影响 *

Effects of capparis spinosa total alkaloid on Wnt3a/β-catenin expressions in mice with systemic sclerosis *

摘要:

目的??研究刺山柑总生物碱对系统性硬皮病小鼠 Wnt 通路相关蛋白 Wnt3a、Wnt1 诱导的信号通 路蛋白 1（WISP1）和 β- 连环蛋白（β-catenin）的调控作用。方法??采用盐酸博莱霉素皮下注射法复制系 统性硬皮病小鼠模型后，给予受试药乳膏冶疗 8 周。酶联免疫吸附试验（ELISA）检测小鼠皮肤组织 Wnt3a 和 WISP1 的浓度，实时荧光定量聚合酶链反应（qRT-PCR）检测小鼠皮肤组织 β-catenin?mRNA 的表达， 免疫组织化学法检测小鼠皮肤组织 β-catenin 蛋白表达。结果??刺山柑总生物碱 450 mg/kg 可降低 Wnt3a 的 浓度； 450 mg/kg和900 mg/kg可降低β-catenin?mRNA和蛋白表达 （ P <0.05） ， 对WISP1浓度无影响 （ P >0.05） 。 结论??刺山柑总生物碱可抑制系统性硬皮病小鼠皮肤组织 Wnt3a 和 β-catenin 的异常表达，对系统性硬皮病 Wnt/β-catenin 通路的过度激活有一定抑制作用。

Abstract:

Objective To explore the effects of capparis spinosa total alkaloid on Wnt pathways related protein Wnt3a, β-catenin and Wnt1-inducible signaling pathway protein 1 (WISP1) expressions in mice with systemic sclerosis (SSc). Methods Subcutaneous injection of bleomycin was injected in BALB/c mice to replicate the SSc model. Capparis spinosa total alkaloid cream (225, 450 and 900 mg/kg) was topically applied to the mice daily for 8 weeks. The levels of Wnt3a and WISP1 were measured by ELISA, the mRNA expression of β-catenin was detected by real-time reverse transcriptase PCR (qRT-PCR), and the β-catenin protein expression was detected by immunohistochemical in skin tissue. Results The level Wnt3a was markedly decreased after administration of 450 mg/kg capparis spinosa total alkaloid, and the mRNA and protein expressions of β-catenin were markedly decreased after administration of 450 and 900 mg/kg capparis spinosa total alkaloid than those in model group mice (all P < 0.05). But the level of WISP1 was not influenced (P > 0.05). Conclusion Capparis spinosa total alkaloid can inhibit the Wnt/β-catenin pathway of SSc mice by down-regulating the expressions of Wnt3a and β-catenin.