中国中西医结合杂志2024，Vol.44Issue(8)：974-982,9.DOI:10.7661/j.cjim.20240614.022
青霉胺联合肝豆汤调控Caspase11-GSDMD通路抑制Wilson病模型神经元焦亡
Penicillamine Combined with Gandou Decoction Regulates Caspase11-GSDMD Pathway to Inhibit Pyroptosis in Wilson Disease Model
摘要
Abstract
Objective To investigate the inhibitory effects and potential mechanisms of penicillamine combined with Gandou Decoction on neuronal pyroptosis in a Wilson disease(WD)model.Methods The in vitro experiments included the following groups,i.e.,the normal group,model group(CuCl2 10 µ mol/L),control group(WEL 20 μ mol/L),and WEL group(CuCl2 10 µ mol/L+WEL 20 µ mol/L).And the in vivo experiments,included the following groups,i.e.,the normal group(0.9％NaCl solution 0.2 mL·10 g-1·d-1),model group(0.9％NaCl solution 0.2 mL·10 g-1·d-1),Gandou Decoction group(0.2 mL·10 g-1·d-1),penicillamine group(0.1 g·kg-1·d-1),and combination treatment group(penicillamine 0.1 g·kg-1·d-1+Gandou Decoction 0.2 mL·10 g-1·d-1).After 4 weeks of administration,motor function was assessed through behavioral experiments,and striatal tissues were collected.Neuronal damage was observed using Fluoro-Jade B(FJB)staining,ultrastructural changes were examined by transmission electron microscopy(TEM),copper content was measured using inductively coupled plasma mass spectrometry(ICP-MS),and microglial activation was assessed by immunofluorescence staining.The expression levels of pyroptosis-related genes and proteins in cells and striatal tissues were determined by RT-qPCR and Western Blot.Results In the in vivo experiments,compared to the normal group,the model group exhibited reduced motor function,increased FJB-positive cells in the striatum(P＜0.01),neuronal swelling,membrane pore formation,microglial activation(P＜0.01),and elevated expression levels of pyroptosis-related genes and proteins(P＜0.05).Compared to the model and penicillamine groups,the combination treatment group showed improved motor function,reduced FJB-positive cells(P＜0.01),intact neuronal cell membranes,intact neuronal cell membranes,and decreased microglial activation(P＜0.01),and lowered expression levels of pyroptosis-related genes and proteins(P＜0.05).In the in vitro experiments,the model group exhibited elevated expression levels of pyroptosis-related genes and proteins compared to the normal group(P＜0.05).The WEL group showed reduced expression levels of pyroptosis-related genes and proteins compared to the model group(P＜0.05).Conclusion Penicillamine combined with Gandou Decoction can effectively reduce neuronal damage in the WD model,and its mechanism is associated with the inhibition of Caspase11-GSDMD pathway-mediated neuronal pyroptosis.关键词
Wilson病/神经元焦亡/半胱氨酸天冬氨酸蛋白酶11-GSDMD通路/肝豆汤/青霉胺/中西医结合Key words
Wilson's disease/neuronal pyroptosis/Caspase11-GSDMD pathway/Gandou Decoction/penicillamine/integrative medicine引用本文复制引用
韩鑫,张亮亮,董健健,文佩华,徐乐文,徐陈陈,程楠,韩咏竹..青霉胺联合肝豆汤调控Caspase11-GSDMD通路抑制Wilson病模型神经元焦亡[J].中国中西医结合杂志,2024,44(8):974-982,9.基金项目
安徽省自然科学基金青年项目(No.2208085QH263) （No.2208085QH263）
安徽省自然科学基金项目(No.2208085MH226) （No.2208085MH226）
安徽省高等学校科学研究项目(No.2023AH050778) （No.2023AH050778）
