[Effect of moxibustion on cognitive function and hippocampal mitochondrial dynamics related proteins in rats with vascular dementia].

Abstract

Objectives: To investigate the effect of moxibustion on hippocampal mitochondrial dynamics-related proteins in rats with vascular dementia (VD), so as to reveal the underlying mechanisms of moxibustion in treating VD.

Methods: SD rats were randomly divided into sham operation, model, moxibustion and medication groups, with 12 rats in each group. The VD model was prepared using an improved bilateral common carotid artery ligation method. Mild moxibstion was applied to "Shenting" (GV24), "Baihui" (GV20) and "Dazhui" (GV14) for 20 min, once daily for 6 days per week. Rats of the medication group were treated with oral administration of nimodipine (12 mg/kg) once daily. All above interventions were performed for 4 weeks. Learning and memory abilities were assessed using Morris water maze test. Histopathological changes of hippocampus was observed with HE staining. Mitochondrial membrane potential (Δψm) and reactive oxygen species (ROS) levels in hippocampal tissue were measured by flow cytometry. The mRNA and protein expression levels of optic atrophy protein 1 (Opa1), mitochondrial fusion protein 1 (Mfn1), mitochondrial fusion protein 2 (Mfn2), dynamics-related protein 1 (Drp1), fission protein 1 (Fis1), mitochondrial fission factor (Mff) in hippocampus was detected by PCR or Western blot, respectively.

Results: Compared with the sham operation group, the escape latency was prolonged (P<0.01), the times of crossing the original platform were reduced (P<0.01), the membrane potential of hippocampus, the mRNA and protein expression levels of Opa1, Mfn1 and Mfn2 in hippocampus were decreased (P<0.01, P<0.001) in the model group, while the average fluorescence intensity of ROS was increased, the mRNA and protein expression levels of Drp1, Fis1 and Mff were increased (P<0.001). In comparison with the model group, the escape latency was significantly shortened (P<0.05), the times of crossing the original platform were increased (P<0.05), the membrane potential of the hippocampus, the mRNA and protein expression levels of Opa1, Mfn1 and Mfn2 were increased (P<0.05, P<0.001) in the moxibustion and medication groups, while the average fluorescence intensity of ROS in the hippocampus, the mRNA and protein expression levels of Drp1, Fis1 and Mff were decreased (P<0.001). The average fluorescence intensity of ROS in the moxibustion group was significantly lower than that in the medication group (P<0.001). HE staining showed loose arrangement of neurons, disappearance of partial nucleolus, and necrocytosis after modeling, which were relatively milder in both moxibustion and medication groups.

Conclusions: Moxibustion can effectively improve the cognitive function of VD rats, and its mechanism may be related to regulating hippocampal mitochondrial dynamics-related proteins, promoting mitochondrial fusion, inhibiting excessive mitochondrial division, thereby improving the imbalance of mitochondrial dynamics and alleviating mitochondrial dysfunction-related conditions.