该研究旨在评估麦角硫因(ergothioneine,ERGO)对D-半乳糖(D-galactose, D-gal)诱导的大鼠氧化应激损伤的保护作用,并探讨其潜在作用机制。选用SD雄性大鼠作为研究对象,通过腹腔注射D-gal溶液进行造模,随机分为5组,即对照组、模型组、ERGO低剂量组(ERGO-L,1.25 mg/kg)、ERGO中剂量组(ERGO-M,2.5 mg/kg)、ERGO高剂量组(ERGO-H,5.0 mg/kg),大鼠每日接受一次相应给药,持续4周。采用比色法检测大鼠血清、肝脏、肾脏和脾脏中脂质氧化产物标志物丙二醛(malondialdehyde,MDA),蛋白质氧化损伤标志物蛋白质羰基(protein carbonyl,PC)和抗氧化酶标志物超氧化物歧化酶(superoxide dismutase,SOD),过氧化氢酶(catalase,CAT)和抗氧化物质还原型谷胱甘肽(reduced glutathione,GSH)的水平。采用16S基因测序和超高效液相串联三重四级杆质谱分析各组大鼠肠道菌群组成和短链脂肪酸(short-chain fatty acids, SCFAs)含量,以评估其潜在的抗氧化作用机制。结果显示,与模型组相比,各给药组可不同程度地显著性降低大鼠血清、肝脏、肾脏和脾脏中MDA和PC水平(P<0.05或P<0.01),并显著性增加SOD、CAT活性和GSH水平(P<0.05或P<0.01);与模型组相比,除了低剂量组对IL-1β水平无显著性降低外,其他剂量组均显著性降低氧化应激损伤大鼠血清中IL-1β、IL-6和TNF-α的水平(P＜0.05或0.01);与模型组相比,氧化损伤大鼠肠道中SCFAs丁酸、异丁酸和戊酸的含量均有显著下降(P<0.01)。与模型组比较,ERGO能显著增加氧化损伤大鼠肠道中SCFAs含量。ERGO给药对D-gal诱导的大鼠氧化应激损伤有显著的保护作用,其作用机制可能为降低炎症反应和通过调控肠道菌群促进SCFAs生成以及直接的抗氧化作用。
This study aimed to evaluate the protective effect of ergothioneine (ERGO) on D-galactose (D-gal)-induced oxidative stress damage in rats and to explore its potential mechanisms.SD male rats were used as research subjects and were modeled by intraperitoneal injection of D-gal solution.They were randomly divided into five groups, including a blank group, a model group, an ERGO low-dose group (ERGO-L, 1.25 mg/kg), an ERGO medium-dose group (ERGO-M, 2.5 mg/kg), and an ERGO high-dose group (ERGO-H, 5.0 mg/kg).Rats received corresponding administrations once daily for 4 weeks.The levels of malondialdehyde (MDA), protein carbonyl (PC), superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH) in rat serum, liver, kidney, and spleen were measured by colorimetry.The composition of the gut microbiota and the content of short-chain fatty acids (SCFAs) in each group of rats were analyzed by 16S sequencing and ultra-high-performance liquid chromatography-tandem triple quadrupole mass spectrometry to evaluate the potential antioxidant mechanism.Results showed that compared with the model group, the administration groups significantly reduced the levels of MDA and PC in rat serum, liver, kidney, and spleen to varying degrees (P<0.05 or P<0.01) and significantly increased the activities of SOD and CAT and the level of GSH (P<0.05 or P<0.01).Except for the low-dose group, which had no significant reduction in IL-1β levels, all other dose groups significantly reduced the levels of IL-1β, IL-6, and TNF-α in the serum of rats with oxidative stress damage (P<0.05 or P<0.01).Compared with the model group, the contents of short-chain fatty acids (SCFAs), including butyrate, isobutyrate, and valerate, were significantly decreased in the gut of rats with oxidative damage (P<0.01).Compared with the model group, ERGO significantly increased the SCFA contents in the gut of rats with oxidative damage.ERGO administration has a significant protective effect on D-gal-induced oxidative damage in rats, and its mechanism may be achieved by reducing inflammation, regulating the gut microbiota to promote the generation of short-chain fatty acids, and direct antioxidant effects.
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