RESUMEN
OBJECTIVE: To discuss the influence of Sailuotong (, SLT) on the Neurovascular Unit (NVUs) of amyloid precursor protein (APP)/presenilin-1(PS1) mice and evaluate the role of gas supplementation in activating blood circulation during the progression of Alzheimer's disease (AD). METHODS: The mice were allocated into the following nine groups: (a) the C57 Black (C57BL) sham-operated group (control group), (b) ischaemic treatment in C57BL mice (the C57 ischaemic group), (c) the APP/PS1 sham surgery group (APP/PS1 model group), (d) ischaemic treatment in APP/PS1 mice (APP/PS1 ischaemic group), (e) C57BL mice treated with aspirin following ischaemic treatment (C57BL ischaemic + aspirin group), (f) C57BL mice treated with SLT following ischaemic treatment (C57BL ischaemic + SLT group), (g) APP/PS1 mice treated with SLT (APP/PS1 + SLT group), (h) APP/PS1 mice treated with donepezil hydrochloride following ischaemic treatment (APP/PS1 ischaemic + donepezil hydrochloride group) and (i) APP/PS1 mice treated with SLT following ischaemic treatment (APP/PS1 ischaemic + SLT group). The ischaemic model was established by operating on the bilateral common carotid arteries and creating a microembolism. The Morris water maze and step-down tests were used to detect the spatial behaviour and memory ability of mice. The hippocampus of each mouse was observed by haematoxylin and eosin (HE) and Congo red staining. The ultrastructure of NVUs in each group was observed by electron microscopy, and various biochemical indicators were detected by enzyme-linked immunosorbent assay (ELISA). The protein expression level was detected by Western blot. The mRNA expression was detected by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: The results of the Morris water maze and step-down tests showed that ischemia reduced learning and memory in the mice, which were restored by SLT. The results of HE staining showed that SLT restored the pathological changes of the NVUs. The Congo red staining results revealed that SLT also improved the scattered orange-red sediments in the upper cortex and hippocampus of the APP/PS1 and APP/PS1 ischaemic mice. Furthermore, SLT significantly reduced the content of Aß, improved the vascular endothelium and repaired the mitochondrial structures. The ELISA detection, western blot detection and qRT-PCR showed that SLT significantly increased the vascular endothelial growth factor (VEGF), angiopoietin and basic fibroblast growth factor, as well as the levels of gene and protein expression of low-density lipoprotein receptor-related protein-1 (LRP-1) and VEGF in brain tissue. CONCLUSIONS: By increasing the expression of VEGF, SLT can promote vascular proliferation, up-regulate the expression of LRP-1, promote the clearance of Aß and improve the cognitive impairment of APP/PS1 mice. These results confirm that SLT can improve AD by promoting vascular proliferation and Aß clearance to protect the function of NVUs.
Asunto(s)
Enfermedad de Alzheimer , Precursor de Proteína beta-Amiloide , Medicamentos Herbarios Chinos , Ratones , Animales , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Ratones Transgénicos , Factor A de Crecimiento Endotelial Vascular , Donepezilo , Péptidos beta-Amiloides/genética , Péptidos beta-Amiloides/metabolismo , Presenilina-1/genética , Presenilina-1/metabolismo , Rojo Congo , Ratones Endogámicos C57BL , Aspirina , Modelos Animales de EnfermedadRESUMEN
Objective To evaluate the objective sleep status of patients with chronic insomnia by cardiopulmonary coupling (CPC) technique, and evaluate the characteristics of cognitive dysfunction to explore the correlation between objective sleep and cognitive dysfunction in patients with chronic insomnia. Methods Forty-three patients with chronic insomnia, admitted to our hospital from October 2017 to April 2019, were enrolled in our study;15 age-, gender-and education-matched healthy volunteers were recruited as control group. All subjects followed their daily routine at home and completed CPC examination. Montreal Cognitive Assessment (MoCA), Auditory Vocabulary Learning Test (AVLT), Trail Making Test (TMT) and Stroop Color Word Test were used to evaluate the general and single cognitive functions, respectively. The correlation of objective sleep with cognitive function was analyzed. Results (1) As compared with those in the control group, high frequency coupling (stable sleep) ratio was significantly decreased, low frequency coupling (un-stable sleep) ratio and extremely low frequency coupling (rapid-eye-movement sleep/waking) ratio were significantly increased, and latency of high frequency coupling was significantly prolonged in chronic insomnia group (P<0.05). (2) Chronic insomnia group had significantly lower MoCA total scores than control group (P<0.05), specifically manifested as decrement of visuospatial ability and execution and attention abilities; specific cognitive test showed that chronic insomnia group performed worse in immediate recall, and had delayed recall of AVLT, longer time consumption in TMT-B, smaller number of wired arrival numbers, and longer time consumption in Stroop color word test than the control group, with significant differences (P<0.05). (3) There was a correlation between CPC sleep structure and Cognitive Function Scale scores in patients with chronic insomnia. Conclusion In patients with chronic insomnia, stable sleep is reduced, un-stable sleep and rapid-eye-movement sleep/waking are increased; the impaired cognition domains are visual space and executive function, attention and memory; disturbed sleep structure aggravates the memory and execution impairment of patients with chronic insomnia.