人参皂苷Rg_1延缓脑衰老机制研究

Research of anti-aging mechanism of ginsenoside Rg_1 on brain

神经系统退行性疾病是老年患者的常见病和多发病。前期研究发现人参皂苷Rg1有明显延缓脑衰老作用,但作用机制并不完全清楚。为研究人参皂苷Rg1抗脑衰老的可能机制,40只雄性SD大鼠随机分为正常组、Rg1正常组、脑衰老模型组、Rg1脑衰老模型组,每组10只(脑衰老模型组:大鼠皮下连续42 d注射D-半乳糖(120 mg·kg-1),qd。Rg1脑衰老模型组:在脑衰老模型复制同时,16 d起开始腹腔注射人参皂苷Rg1(20 mg·kg-1)27 d,qd。Rg1正常组:大鼠皮下注射等量生理盐水,16 d起开始腹腔注射人参皂苷Rg1(20 mg·kg-1)27 d,qd。正常组:注射等时与等量生理盐水。模型复制结束或药物注射完成第2天进行相关实验。通过水迷宫实验、β-半乳糖苷酶(SA-β-Gal)染色实验、ELISA实验、酶标比色法实验、Southern blotting和PCR-ELISA实验检测各组大鼠的空间记忆能力、脑衰老情况、海马区IL-1和IL-6炎症因子变化、海马区抗氧化指标SOD和GSH变化以及海马区端粒长度和端粒酶活性变化。结果脑衰老模型组大鼠空间记忆能力减退,脑组织切片显示SA-β-Gal染色阳性颗粒增多,海马区SOD活性降低,GSH含量减少,IL-1,IL-6含量增多,端粒长度缩短,端粒酶活性降低。Rg1脑衰老模型组大鼠空间记忆能力有明显改善,SA-β-Gal染色蓝色颗粒减少,海马区SOD活性增高,GSH含量增多,IL-1,IL-6含量减少,端粒长度缩短受到阻止,端粒酶活性增高。Rg1正常组大鼠与正常组大鼠相比空间记忆能力增强,SA-β-Gal染色蓝色颗粒减少,海马区IL-1,IL-6含量减少。结果表明人参皂苷Rg1可能通过调节端粒系统、炎症因子水平和抗氧化作用发挥延缓脑衰老作用。

Neurodegenerative disease is common and frequently occurs in elderly patients. Previous studies have shown that ginsenoside Rg1 was able to inhibit senescent of brain,but the mechanism on the brain during the treatment remains elucidated. To study the mechanism of ginsenoside Rg1 in the process of anti-aging of brain,forty male SD rats were randomly divided into normal group,Rg1 normal group,brain aging model group and Rg1 brain aging model group,each group with 10 rats（ brain aging model group： subcutaneous injection of D-galactose（ 120 mg·kg^-1）,qd for 42 consecutive days; Rg1 brain aging model group： while copying the same test as that of brain aging model group,begin intraperitoneal injection of ginsenosides Rg1（ 20 mg·kg^-1） qd for 27 d from 16 d. Rg1 normal group： subcutaneous injection of the same amount of saline; begin intraperitoneal injection of ginsenosides Rg1（ 20 mg·kg^-1） qd for 27 d from 16 d. Normal： injected with an equal volume of saline within the same time. Perform the related experiment on the second day after finishing copying the model or the completion of the first two days of drug injections）. Learning and memory abilities were measured by Morris water maze. The number of senescent cells was detected by SA-β-Gal staining while the level of IL-1 and IL-6 proinflammatory cytokines in hippocampus were detected by ELISA. The activities of SOD,contents of GSH in hippocampus were quantified by chromatometry. The change of telomerase activities and telomerase length were performed by TRAP-PCR and southern blotting assay,respectively. It is pointed that,in brain aging model group,the spatial learning and memory capacities were weaken,SA-β-Gal positive granules increased in section of brain tissue,the activity of antioxidant enzyme SOD and the contents of GSH decreased in hippocampus,the level of IL-1 and IL-6 increased in hippocampus,while the length of telomere and the activity of telomerase decreased in hippocampus. Rats of Rg1 brain aging group had their spatial learning and memory capacities enhanced,SA-β-Gal positive granules in section of brain tissue decreased,the activity of antioxidant enzyme SOD and the contents of GSH increased in hippocampus,the level of IL-1 and IL-6 in hippocampus decreased,the length contraction of telomere suppressed while the change of telomerase activity increased in hippocampus. Compared with that of normal group,the spatial learning and memory capacities were enhanced in Rg1 normal group,SA-β-Gal positive granules in section of brain tissue decreased in Rg1 normal group,the level of IL-1 and IL-6 in hippocampus decreased in Rg1 normal group. The results indicated that improvement of antioxidant ability,regulating the level of proinflammatory cytokines and regulation of telomerase system may be the underlying anti-aging mechanism of Ginsenoside Rg1.