茶褐素对D-半乳糖致衰老小鼠脑组织代谢组学的影响

本研究通过D-半乳糖皮下注射建立小鼠衰老模型，利用免疫组化和UHPLC-QE-MS代谢组学技术检测正常对照小鼠、D-半乳糖模型小鼠、茶褐素（预防和治疗）干预小鼠的脑组织，探究茶褐素对D-半乳糖致衰老小鼠脑组织免疫组化的影响，筛选茶褐素对衰老小鼠作用的差异代谢物并分析其涉及的代谢通路。结果表明:茶褐素干预后，衰老小鼠脑组织中的乙酰胆碱转移酶阳性表达面密度显著升高（P<0.05）；预防性给予茶褐素可以显著调节衰老小鼠脑组织中的17种代谢物，主要涉及甘油磷脂代谢、组氨酸代谢、TCA循环、乙醛酸和二羧酸代谢、β-丙氨酸代谢5条代谢通路；茶褐素治疗可以显著调节衰老小鼠脑组织中的32种代谢物，主要涉及甘油磷脂代谢，组氨酸代谢，牛磺酸和亚牛磺酸代谢，缬氨酸、亮氨酸和异亮氨酸的降解，苯丙氨酸、酪氨酸和色氨酸的生物合成5条通路。其中，肌肽、LysoPC(P-18:1(9Z))、PS(20:5(5Z,8Z,11Z,14Z,17Z)/18:1(9Z))、PC(15:0/15:0)、D-阿拉伯糖-5-磷酸盐、硫酸胆固醇和二磷酸腺苷核糖7个代谢物以及甘油磷脂代谢和组氨酸代谢2条代谢通路为茶褐素预防组和治疗组共有。茶褐素可以通过调节小鼠体内脂类代谢，能量代谢，氨基酸代谢等过程，从而起到抗衰老作用。

Effects of Theabrownin on Brain Metabolites in D-galactose-induced Aging in Mice

The objective of the study is to investigate the effect of theabrownin on the immunohistochemistry of brain tissue in aging mice, screen the differential metabolites and analyze the metabolic pathways involved. A mouse aging model was established by subcutaneous injection of D-galactose in mice. Immunohistochemical and UHPLC-QE-MS metabolomics techniques were used to detect brain samples of normal control mice, D-galactose model mice and theabrownin-treated (pretreatment and treatment) mice. The results showed that the areal density of choline acetyltransferase positive expression was significantly increased (P<0.05) after theabrownin intervention. Prophylactic administration of theabrownin could significantly regulate 17 metabolites in brain tissue of aging mice, mainly involving glycerophospholipid metabolism, histidine metabolism, TCA cycle, glyoxylate and dicarboxylate metabolism and beta-alanine metabolism. Theabrownin treatment could significantly regulate 32 metabolites in brain tissue of aging mice, mainly involving glycerophospholipid metabolism, histidine metabolism, taurine and hypotaurine metabolism, valine, leucine and isoleucine degradation, phenylalanine, tyrosine and tryptophan biosynthesis. Carnosine, LysoPC(P-18:1(9Z)), PS(20:5(5Z,8Z,11Z,14Z,17Z)/18:1(9Z)), PC(15:0/15:0), D-arabinose 5-phosphate, cholesterol sulfate, adenosine diphosphate ribose, glycerophospholipid metabolism and histidine metabolism were common in the theabrownin pretreatment and theabrownin treatment groups. Theabrownin can play an anti-aging role by regulating lipid metabolism, energy metabolism, amino acid metabolism and other processes in mice.