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目的:以川芎嗪、原儿茶酸为前体原料,运用药物拼合理论,合成川芎嗪-原儿茶酸络合物,并对其进行初步体内外缺血性脑损伤活性研究。方法:以川芎嗪(Tetramethylpyrazine,TMP)和原儿茶酸(Protocatechuic acid,PCA)为原料合成川芎嗪-原儿茶酸络合物(Tetramethylpyrazine-Protocatechuic acid,TP),运用UV、1H-NMR、13C-NMR、MS、X-Ray确定该化合物的结构。通过①鸡胚绒毛尿囊膜血管生成(Chicken chorioallantoic membrane,CAM)模型观察TP对新生血管生长的影响;②MTT法测定TP对原代培养的正常胎鼠皮层神经细胞、谷氨酸(Glutamate,Glu)和NO损伤神经细胞模型的影响;③TP对小鼠断头张口呼吸时间的影响等实验初步观察其对缺血性脑损伤的拮抗作用。结果:确定TMP和PCA两个分子片断之间借助一个O-H…O氢键和一个O-H…N氢键连接;TP对新生血管的生长具有显著的促进作用,改善Glu、NO对神经细胞的损伤,并能显著延长小鼠断头后张口呼吸时间。结论:由TMP和PCA拼合而成的TP对缺血性脑损伤具有明显改善作用,显示了其良好的新药开发研究前景。
OBJECTIVE: To synthesize tetramethylpyrazine-protocatechuic acid complex with tetramethylpyrazine and protocatechuic acid as precursors by using drug combination theory, and to study its preliminary activity in vitro and in vivo. Methods: Tetramethylpyrazine-Protocatechuic acid (TP) was synthesized from tetramethylpyrazine (TMP) and protocatechuic acid (PCA). UV, 1H-NMR, 13C-NMR, MS, X-Ray to confirm the structure of the compound. The effects of TP on neovascularization were observed by ① chick chorioallantoic membrane (CAM) model; ②TT assay was used to determine the effects of TP on the proliferation of primary cultured fetal rat cortical neurons, Glutamate (Glu) ) And NO injury; ③ The effect of TP on the respiration time of the decapitation mouth in mice was preliminary observed by observing its antagonism on ischemic brain injury. Results: It was confirmed that two molecular fragments of TMP and PCA were linked by one OH ... O hydrogen bond and one OH ... N hydrogen bond. TP could significantly promote the growth of neovascularization and improve the injury of nerve cells by Glu and NO, And can significantly prolong the post-decapitation mouth breathing time of mice. Conclusion: TP combined by TMP and PCA has a significant improvement on ischemic brain injury, showing its good prospects for the development of new drugs.