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| Effect of electro-acupuncture intervention on mitochondrial fission in diabetic mice with postoperative cognitive dysfunction |
| YAN Ruyu DING Lingling CHEN Mengjie LUO Jiansheng NING Jiaqi ZHOU Ruiling YU Bo |
| Department of Anesthesiology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, China |
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Abstract Objective To observe the effect of electro-acupuncture intervention on mitochondrial fission in diabetic mice with postoperative cognitive dysfunction (POCD). Methods Thirty-nine SPF-grade C57BL/6 male mice of body weight(20±2) g aged four to six weeks injected intraperitoneally with streptozotocin after 16 weeks of high-fat and high-sugar diet with fasting blood glucose≥11.1 mmol/L after one week, that is, they were experimental animals with diabetes mellitus type 2 (no mice died). Then they were divided into the control group, the model group, and the electro-acupuncture group by random number table method, 13 mice in each group. The control group did not do any other intervention except grasp and fixation. POCD model was established by tibial fracture intra- medullary fixation between model group and electroacupu- ncture group (no mice death). Compared with the control group, the cognitive ability of the model group decreased and the model was considered successful. In the electro-acupuncture group, shéntíng, bǎihuì, nèiguān, and zúsānlǐ were treated with electro-acupuncture intervention two weeks before surgery, and the needles were retained for 30 min each time for five consecutive days every week. The cognitive function of mice was evaluated by open field test and fear conditioning test one day after operation. Hematoxylin-eosin staining was used to observe the pathology of hippocampal CA1 region. The number of neurons was observed by Nissl staining. The content of adenosine triphosphate (ATP) was detected by chemiluminescence. Mitochondrial membrane potential (MMP) was detected by flow cytometry. Western blot analysis was performed to detect the protein expression levels of dynamin-related protein 1(Drp1), p-Drp1 Ser616, and p-Drp1 Ser637 in the hippocampus of mice. Results Compared with the control group, the freezing time of the context test in the model group was reduced (P＜0.05). Compared with the model group, the freezing time of the context test in the electro-acupuncture group was increased (P＜0.05). Compared with the control group, the damage of neurons in CA1 region of the model group was aggravated and the number of neurons was decreased (P＜0.05). Compared with the model group, the damage of neurons in CA1 region was reduced and the number of neurons was increased in electro-acupuncture group (P＜0.05). Compared with the control group, ATP content and MMP in the model group were decreased (P＜0.05). Compared with the model group, ATP content and MMP in electro-acupuncture group were increased (P＜0.05). Compared with the control group, the expression level of p-Drp1 Ser616 protein in hippocampus of model group was increased, while the expression level of p-Drp1 Ser616 protein was decreased (P＜0.05). Compared with the the model group, the expression level of p-Drp1 Ser616 protein in hippocampus of the electro-acupuncture group was decreased, and the expression level of p-Drp1 Ser616 protein was increased (P＜0.05). Conclusion Electro-acupuncture can improve the learning and memory ability of POCD in diabetic mice and reduce the neuronal damage. The mechanism may be related to the reduction of Drp1-mediated mitochondrial hyperfission and the improvement of hippocampal mitochondrial function.
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