中国药理学通报2024,Vol.40Issue(4):687-694,8.DOI:10.12360/CPB202310018
眼镜蛇神经毒素分离纯化及其经大鼠直肠给药吸收的实验研究
The experimental studies on isolation and purification of cobra neurotoxin and its absorption via rectal administration in rats
摘要
Abstract
Aim To isolate and purify neurotoxin from the crude venom of cobra by chromatographic tech-niques and to explore the absorption and analgesic ac-tivity of neurotoxin after administration via the rectal route in rats.Methods Two-step CM Sepharose Fast Flow cation exchange chromatography and Sephadex G-50 gel filtration chromatography were used to isolate and purify neurotoxin.Immunohistochemical technique was used to observe the distribution of neurotoxin in rat rectal tissue.Shotgun mass spectrometry and database were applied to detect rat plasma neurotoxin fragments.HE staining was used to observe the effect of neurotox-in on the structure of rat rectal tissue.The torsion ace-tate method was employed to determine the analgesic activity of neurotoxin after rectal administration.Re-sults Electrophoretically pure neurotoxin was ob-tained by chromatographic separation and purification.The distribution of neurotoxin in the rectal mucosal tis-sue was obvious after 3 h of rectal administration of neurotoxin,and the positive area ratio,average optical density value,and H-SCORE value were significantly different from those of the control group(P<0.01).Mass spectrometry detected neurotoxin-related frag-ments in rat plasma.HE staining showed that neuro-toxin did not damage the rectal tissues of rats,and there were no obvious pathological changes in the tissue structure.50%inhibition of torsion in mice after 3 h rectal administration of neurotoxin was determined by the acetic acid torsion method,suggesting an analgesic activity.Conclusions Cobra neurotoxin can be ab-sorbed into bloodstream through rectum and exert anal-gesic effects,which provides an experimental basis for the subsequent study of cobra neurotoxin in rectal de-livery formulations.关键词
眼镜蛇/神经毒素/直肠给药/免疫组化/质谱/镇痛Key words
cobra/neurotoxin/rectal administration/immunohistochemistry/mass spectrometry/analgesia分类
医药卫生引用本文复制引用
张昊,廖明,张学荣,周怡,孔露平,胡少聪,肖曼琪,张子彦,罗小玲..眼镜蛇神经毒素分离纯化及其经大鼠直肠给药吸收的实验研究[J].中国药理学通报,2024,40(4):687-694,8.基金项目
国家自然科学基金资助项目(No 82260386) (No 82260386)