OBJECTIVE: To observe the effect of Huayu Tongluo moxibustion on the NOD-like receptor protein 3 (NLRP3)/cysteine-aspartic acid protease-1 (Caspase-1)/gasdermin D (GSDMD) signaling pathway in rats with vascular dementia (VD), and to explore its mechanism in improving learning and memory ability and alleviating neuronal injury in the hippocampal CA1 region. METHODS: A total of 80 SPF-grade male Wistar rats were included. Three rats were excluded based on the Morris water maze test. From the remaining rats, 12 were randomly selected as the sham operation group. The rest were used to establish VD models via modified bilateral common carotid artery ligation. Thirty-six successfully modeled rats were randomly divided into a model group, a medication group, and a moxibustion group, with 12 rats in each group. The medication group was treated with nimodipine solution (12 mg/kg) via gavage. The moxibustion group was treated with Huayu Tongluo moxibustion. The suspended moxibustion was applied at Shenting (GV24) and Dazhui (GV14), and aconite cake-separated moxibustion was applied at Baihui (GV20), with each acupoint treated for 20 min. All treatments were administered once daily for 21 consecutive days. Before and after modeling, and after intervention, the Morris water maze test was used to assess cognitive function. After intervention, the activation and morphology of microglia in the hippocampal CA1 region were observed by immunofluorescence. Ultrastructure of hippocampal CA1 neurons was examined by transmission electron microscopy. Western blot was used to detect protein expression of NLRP3, apoptosis-associated speck-like protein (ASC), Caspase-1, GSDMD, and interleukin-1β (IL-1β) in the hippocampal CA1 region. ELISA was used to detect the content of IL-6, IL-8, and tumor necrosis factor-α (TNF-α) in the hippocampal CA1 region. RESULTS: Compared with the sham operation group, the model group showed longer mean escape latency (P<0.01) and fewer platform crossings (P<0.01); the microglial processes in the hippocampal CA1 region were thickened, cytoplasm was hypertrophic, and relative fluorescence intensity of ionized calcium-binding adapter molecule 1 (IBA-1) was increased (P<0.05); the neuronal ultrastructure in the CA1 region was severely damaged, rough endoplasmic reticulum was swollen, mitochondria were deformed and swollen, some cristae were ruptured or dissolved, showing vacuolar changes; the protein expression of NLRP3, ASC, Caspase-1, GSDMD, and IL-1β, as well as levels of IL-6, IL-8, and TNF-α were significantly elevated (P<0.001). Compared with the model group, both the medication group and the moxibustion group showed shortened mean escape latency (P<0.01) and increased platform crossings (P<0.01); the microglial processes were thinner, and IBA-1 fluorescence intensity was decreased (P<0.05); the neuronal ultrastructure in the CA1 region was partially improved; the protein expression of NLRP3, ASC, Caspase-1, GSDMD, and IL-1β, and levels of IL-6, IL-8, and TNF-α were significantly reduced (P<0.001). Compared with the medication group, the moxibustion group showed shortened mean escape latency (P<0.05) and more platform crossings (P<0.05); the IBA-1 fluorescence intensity was decreased (P<0.05); the neuronal ultrastructure in the CA1 region was improved; the protein expression of NLRP3, ASC, Caspase-1, GSDMD, and IL-1β, as well as levels of IL-6, IL-8, and TNF-α, were significantly lower (P<0.001). CONCLUSION The Huayu Tongluo moxibustion could enhance learning and memory abilities in VD rats, inhibit excessive activation of microglia, and alleviate neuronal injury in the hippocampal CA1 region. Its mechanism may involve modulation of the NLRP3/Caspase-1/GSDMD signaling pathway, reduction of inflammatory responses.
Animals ; Male ; Dementia, Vascular/physiopathology* ; Rats ; Signal Transduction ; Moxibustion ; Rats, Wistar ; CA1 Region, Hippocampal/injuries* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Caspase 1/genetics* ; Memory ; Humans ; Neurons/metabolism* ; Learning

Objective To examine the clinical efficacy of Tongtiao Xinshen acupuncture combined with Wenyang Bushen moxibustion in the treatment of vascular dementia(VD),and its effects on event-related potential P300,neuron specific enolase(NSE),and acetylcholinesterase(AChE).Methods Totally 60 patients diagnosed with VD were divided into acupuncture and moxibustion group and the Western medicine group according to random number table method,with 30 patients in each group.Both groups received basic Western medicine treatments such as blood pressure regulation,blood glucose regulation,and blood lipid regulation;Western medicine group was given donepezil hydrochloride tablets,5 mg each time,once a day,orally;in the acupuncture and moxibustion group,on the basis of the treatment of the Western medicine group,Tongtiao Xinshen acupuncture was combined with Wenyang Bushen moxibustion,once a day,6 times a week;the treatment for both groups lasted for 4 weeks.The scores of Mini Mental State Examination(MMSE)and Activities of Daily Living(ADL)in two groups of patients were evaluated before and on the day after treatment.The event-related potential P300 was measured and the abnormal detection rate changes of MMSE and P300 were determined.Safety indicators of both groups were monitored.Results Compared with before treatment,the scores of MMSE and ADL in the two groups significantly increased(P＜0.05),the latency of P300 in the acupuncture and moxibustion group decreased and the amplitude of P300 increased(P＜0.05),and NSE and AChE levels decreased(P＜0.05).Compared with the Western medicine group,after treatment,MMSE score,ADL score and the amplitude of P300 in the acupuncture and moxibustion group increased,the latency of P300 decreased,and the levels of NSE and AChE decreased(P＜0.05).The detection rate of P300 latency abnormalities in patients was significantly higher than that of MMSE abnormalities(P＜0.05);compared with before treatment,the abnormal rate of P300 latency and MMSE score of patients in the acupuncture and moxibustion group decreased(P＜0.05).No significant adverse reactions were observed in both groups.Conclusion Tongtiao Xinshen acupuncture combined with Wenyang Bushen moxibustion can enhance cognitive function and everyday life abilities.The mechanism may be related to the reduction of NSE and AChE levels,and event-related potential P300 is more sensitive than MMSE in determining VD and cognitive ability.

Objective To examine the clinical efficacy of Tongtiao Xinshen acupuncture combined with Wenyang Bushen moxibustion in the treatment of vascular dementia(VD),and its effects on event-related potential P300,neuron specific enolase(NSE),and acetylcholinesterase(AChE).Methods Totally 60 patients diagnosed with VD were divided into acupuncture and moxibustion group and the Western medicine group according to random number table method,with 30 patients in each group.Both groups received basic Western medicine treatments such as blood pressure regulation,blood glucose regulation,and blood lipid regulation;Western medicine group was given donepezil hydrochloride tablets,5 mg each time,once a day,orally;in the acupuncture and moxibustion group,on the basis of the treatment of the Western medicine group,Tongtiao Xinshen acupuncture was combined with Wenyang Bushen moxibustion,once a day,6 times a week;the treatment for both groups lasted for 4 weeks.The scores of Mini Mental State Examination(MMSE)and Activities of Daily Living(ADL)in two groups of patients were evaluated before and on the day after treatment.The event-related potential P300 was measured and the abnormal detection rate changes of MMSE and P300 were determined.Safety indicators of both groups were monitored.Results Compared with before treatment,the scores of MMSE and ADL in the two groups significantly increased(P＜0.05),the latency of P300 in the acupuncture and moxibustion group decreased and the amplitude of P300 increased(P＜0.05),and NSE and AChE levels decreased(P＜0.05).Compared with the Western medicine group,after treatment,MMSE score,ADL score and the amplitude of P300 in the acupuncture and moxibustion group increased,the latency of P300 decreased,and the levels of NSE and AChE decreased(P＜0.05).The detection rate of P300 latency abnormalities in patients was significantly higher than that of MMSE abnormalities(P＜0.05);compared with before treatment,the abnormal rate of P300 latency and MMSE score of patients in the acupuncture and moxibustion group decreased(P＜0.05).No significant adverse reactions were observed in both groups.Conclusion Tongtiao Xinshen acupuncture combined with Wenyang Bushen moxibustion can enhance cognitive function and everyday life abilities.The mechanism may be related to the reduction of NSE and AChE levels,and event-related potential P300 is more sensitive than MMSE in determining VD and cognitive ability.