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ObjectiveTo explore the mechanism of Gegen Qinliantang （GQT） in improving ectopic lipid accumulation in the liver of db/db mice with type 2 diabetes mellitus （T2DM） by regulating the adenosine monophosphate-activated protein kinase （AMPK）-forkhead box O3a （FoxO3a） autophagy axis， to provide a scientific basis for clarifying the hypoglycemic mechanism of GQT and its clinical application. MethodSeventy-five spontaneous T2DM db/db mice and 15 normal db/m mice were selected and maintained on a regular diet for one week， followed by the measurement of blood glucose. They were then randomly divided into six groups， with 15 mice in each group， including normal group （0.2 g·kg-1 saline）， metformin group （0.2 g·kg-1）， high-， medium， and low-dose GQT group （31.9， 19.1， 6.9 g·kg-1）， and model group （0.2 g·kg-1 saline）. The mice were orally administered the corresponding drugs once daily for 12 weeks. Fasting blood glucose （FBG） and glycated hemoglobin （HbA1c） were detected. Fasting insulin （FINS） and free fatty acid （FFA） levels were measured by enzyme-linked immunosorbent assay （ELISA）. Pathological changes in liver tissues were observed by hematoxylin-eosin （HE） staining. The protein expression levels of phosphorylated （p）-AMPK， p-FoxO3a， and autophagy-related proteins microtubule-associated protein 1 light chain 3 Ⅱ （LC3Ⅱ） and p62 were detected using Western blot. Immunofluorescence was used to detect the expression of hypoxia-inducible factor-1α （HIF-1α） in liver tissues. Real-time polymerase chain reaction （Real-time PCR） was performed to detect the mRNA expression of AMPK， FoxO3a， and LC3 in liver tissues. ResultCompared with the normal group， the model group showed pathological changes in liver tissues， increased FBG， HbA1c， FINS， and FFA levels （P<0.01）， increased protein expression levels of p-AMPK， p62， and HIF-1α， decreased protein expression levels of p-FoxO3a and LC3Ⅱ in liver tissues （P<0.01）， decreased mRNA expression of AMPK， and increased expression of FoxO3a （P<0.01）. Compared with the model group， the treatment groups showed relieved liver tissue lesions and decreased FBG， HbA1c， FINS， and FFA levels （P<0.01）. The expression of p-AMPK， p62， and HIF-1α increased， while the expression of p-FoxO3a showed a dose-dependent decrease in the high-dose GQT group. The expression of LC3Ⅱ increased in the metformin group and the high-dose GQT group （P<0.01）. The mRNA expression of AMPK showed a dose-dependent increase， and the expression of FoxO3a showed a dose-dependent decrease in the treatment groups （P<0.01）. ConclusionGQT can improve ectopic lipid accumulation in the liver of T2DM db/db mice， which may be related to the regulation of the AMPK-FoxO3a autophagy axis.
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Neurodegenerative disease is a type of disease characterized by the progressive loss of neurons, the cause of which is not clear. Aquaporin-4 (AQP4) is a member of the aquaporin family, which plays an important role in maintaining water homeostasis in the brain. In recent years, researchers found that AQP4 has the functions of draining brain metabolic wastes and participating in material exchange through the glmphatic system. This review aims to summarize the current researches of AQP4 in the pathogenesis and progression of neurodegenerative diseases such as Parkinson′s disease and Alzheimer′s disease, and to propose future research directions.
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Parkinson's disease (PD), the second most common neurodegenerative disorder after Alzheimer's disease, is characterized by the loss of nigral dopaminergic neurons. PD leads to a series of clinical symptoms, including motor and non-motor disturbances. α-synuclein, the major component of Lewy bodies, is a hallmark lesion in PD. In this review, we concentrate on presenting the latest research on the structure, distribution, and function of α-synuclein, and its interactions with PD. We also summarize the clinic applications of α-synuclein, which suggest its use as a biomarker, and the latest progress in α-synuclein therapy.
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alfa-Sinucleína , Doença de Alzheimer , Neurônios Dopaminérgicos , Corpos de Lewy , Doenças Neurodegenerativas , Doença de ParkinsonRESUMO
Objective To explore the effect of Baihe Zhimu Tang(百合知母汤,BZT) on the airway inflammation in bronchial asthma rats.Methods Forty Wistar rats were randomized into control group,asthma model group,BZT group and dexamethasone (DX) group with 10 rats in each group.The bronchial asthma rat model was built by intraperitoneal injection of 10％ ovalbumin (OVA) and ultrasonic atomizing inhalation of 2％ OVA except for the control group.Thirty minutes before every ultrasonic atomizing inhalation,the BZT group was given BZT 3.68 g/(kg · d) by gastric perfusion;the DX group was administered DX injection 1.2 mg/(kg · d) by gastric perfusion;as for the control group and asthma model group,they were given normal saline of the same volume;all groups were intervened for 14 days.After that,HE staining was used to observe the pathological changes of lung tissue,the levels of interleukin-2 (IL-2) and interleukin-4 (IL-4) were measured,and the cell cycle and calcineurin (CaN) activity were observed in separated peripheral blood lymphocytes.Results For the asthma model group,there was a lot of inflammatory cell infiltration in the bronchial wall under light microscope,the content of IL-4 in the plasma was higher than that in the control group,while the content of IL-2 decreased,the proportion of G0/G1 phase lymphocytes decreased,the proportion of S phase and G2/M increased,and the CaN activity of lymphocytes increased significantly (P ＜ 0.05).For the BZT group,there was only a small amount of inflammatory cell infiltration in the lung tissue under light microscope,the IL-4 level in the plasma was lower than that in the asthma model group,while the IL-2 content increased,the proportion of G0/G1 phase lymphocytes increased,the proportion of S phase and G2/M decreased significantly,and the CaN activity of lymphocytes decreased significantly (P ＜ 0.05).Conclusion BZT could reduce lymphocyte proliferation,decrease IL-4 level and reduce airway inflammation by reducing CaN activity in peripheral blood lymphocytes of bronchial asthma rats.