Effects of acupuncture plus medication on hippocampus SIRT1 and FOXO3a expression, MDA content, and SOD activity of rats with Alzheimer disease / 针灸推拿医学（英文版）

ABSTRACT

Objective: To observe the effect of the acupuncture plus medication on the expression of silent information regulator of transcription 1 (SIRT1) and transcription factor forkhead box protein O3a (FOXO3a) in the hippocampus, the malondialdehyde (MDA) content, and the superoxide dismutase (SOD) activity of rats with Alzheimer disease (AD), and to explore the possible mechanism of combining acupuncture and medication in improving AD-related neurological symptoms. Methods: Sixty male Sprague-Dawley rats were divided into a normal group, a model group, an electroacupuncture (EA) group, a drug group, and an acupuncture-medication combined group by the random number table method, with 12 rats in each group. The model was established by micro-injection of streptozotocin into the bilateral lateral ventricles. After successful modeling, rats in the EA group received EA at Zusanli (ST36) and Dazhui (GV14), those in the drug group received intragastric administration of resveratrol at a dose of 44 mg/(kg·bw), and those in the acupuncture- medication combined group received the combined intervention of EA and resveratrol. Rats in each group received intervention once a day for 4 consecutive weeks. Morris water maze was used to detect the rat behavioral changes. Nissl staining method was used to observe the cell morphology and changes in the number of rat hippocampal neurons. Western blotting and immunohistochemical staining methods were used to observe the expression changes of SIRT1 and FOXO3a. The thiobarbituric acid method was used to detect the MDA content. SOD activity was determined by the hydroxylamine method. Results: Compared with the normal group, the escape latency was significantly prolonged (P<0.05); the percentage of stay in the target quadrant was reduced (P<0.05), the hippocampal neuronal cells were shrunken, nucleoli were unclear, and cell number was reduced (P<0.05); the SIRT1 expression and SIRT1 positive cell number were decreased, while the FOXO3a expression and FOXO3a positive cell number were increased significantly (P<0.05); the MDA content was increased significantly, and the SOD activity was decreased significantly (P<0.05) in the model group. Compared with the model group, the escape latency was shortened (P<0.05); the percentage of stay in the target quadrant was increased (P<0.05); the shape and number of hippocampal neurons tended to be normal (P<0.05); the SIRT1 protein expression and the SIRT1 positive cell numbers were increased, the FOXO3a protein expression and the FOXO3a positive cell number were decreased (P<0.05); the MDA content was significantly decreased, and the SOD activity was significantly increased (P<0.05) in the EA group, the drug group, and the acupuncture-medication combined group. The changes in the acupuncture-medication combined group were more obvious (P<0.05). Conclusion: Both EA and resveratrol improve the learning and memory ability of AD rats by regulating the expression of SIRT1 and FOXO3a and improving the levels of MDA and SOD in the hippocampus and protect the hippocampal neurons, while the combined use of EA and medication is more effective than EA or resveratrol alone, suggesting that this combined treatment is more effective in AD treatment.