RESUMO
The theory of kidney storing essence storage, an important part of the basic theory of traditional Chinese medicine(TCM), comes from the Chapter 9 Discussion on Six-Plus-Six System and the Manifestations of the Viscera in the Plain Questions, which says that "the kidney manages closure and is the root of storage and the house of Jing(Essence)". According to this theory, essence is the fundamental substance of human life activities and it is closely related to the growth and development of the human body. Alzheimer's disease(AD) is one of the common neurodegenerative diseases, with the main pathological features of Aß deposition and Tau phosphorylation, which activate neurotoxic reactions and eventually lead to neuronal dysfunction and cell death, severely impairing the patient's cognitive and memory functions. Although research results have been achieved in the TCM treatment of AD, the complex pathogenesis of AD makes it difficult to develop the drugs capable of curing AD. The stem cell therapy is an important method to promote self-repair and regeneration, and bone marrow mesenchymal stem cells(BMSCs) as adult stem cells have the ability of multi-directional differentiation. By reviewing the relevant literature, this paper discusses the association between BMSCs and the TCM theory of kidney storing essence, and expounds the material basis of this theory from the perspective of molecular biology. Studies have shown that TCM with the effect of tonifying the kidney in the treatment of AD are associated with BMSCs. Exosomes produced by such cells are one of the main substances affecting AD. Exosomes containing nucleic acids, proteins, and lipids can participate in intercellular communication, regulate cell function, and affect AD by reducing Aß deposition, inhibiting Tau protein phosphorylation and neuroinflammation, and promoting neuronal regeneration. Therefore, discussing the prevention and treatment of exosomes and AD based on the theory of kidney storing essence will provide a new research idea for the TCM treatment of AD.
Assuntos
Doença de Alzheimer , Exossomos , Adulto , Humanos , Doença de Alzheimer/prevenção & controle , Doença de Alzheimer/tratamento farmacológico , Exossomos/metabolismo , Exossomos/patologia , Rim/patologia , Medicina Tradicional Chinesa , NeurôniosRESUMO
This study is to investigate the effects of sophoridine on NF-kappaB signaling pathway in kidney tissue of endotoxemia mice and the mechanism involved. BALB/c mice were challenged with lipopolysaccharide (LPS) caudal vein injection, then sophoridine was administered by intraperitoneal injection. Totally 50 mice were divided into 5 groups: control group, LPS model group, sophoridine treatment 12 mg x kg(-1) group, 6 mg x kg(-1) group and 3 mg x kg(-1) group. All animals were sacrificed at 6 hours after treatment. Kidney and blood samples were harvested. IKKbeta mRNA and TNF-alpha mRNA expression of renal tissue was measured by the reverse transcription polymerase chain reaction (RT-PCR), and phosphorylation IKKbeta protein (pIKKbeta) was detected by immunohistochemistry. NF-kappaB P65 protein expression and distribution of renal tissue were observed by Western blotting and immunofluorescence laser confocal microscopy. Serum TNF-alpha level was detected by radioimmunoassay. The results showed that the sophoridine significantly reduced the expression of IKKbeta mRNA and pIKKbeta protein, and inhibited the expression of NF-kappaB P65 protein and decreased the entry nuclear rate of NF-kappaB P65 in the renal tissue of endotoxemia mice. Thereby the renal TNF-alpha mRNA expression and serum TNF-alpha level were significantly reduced. These results suggest that sophoridine could inhibit inflammatory reaction induced by LPS through inhibiting activation of NF-kappaB signaling pathway.
Assuntos
Alcaloides/farmacologia , Endotoxemia/metabolismo , Quinase I-kappa B/metabolismo , Quinolizinas/farmacologia , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Antitoxinas/farmacologia , Endotoxemia/sangue , Endotoxemia/induzido quimicamente , Endotoxemia/genética , Feminino , Quinase I-kappa B/genética , Rim/metabolismo , Lipopolissacarídeos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fosforilação , RNA Mensageiro/metabolismo , Distribuição Aleatória , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/genética , MatrinasRESUMO
OBJECTIVE: To study the effect of maternal isolation stress on the epilepsy susceptibility in young rats and the possible mechanism. METHODS: Sixty Sprague-Dawley young rats were randomly divided into a normal control and two maternal isolation groups that were subjected to maternal isolation for 15 min or 3 hrs daily on postnatal days 2-17. On postnatal day 18, an amygdala kindling test was performed to induce seizures. The expression of GABA(A) receptor α1 in the hippocampus was determined by immunohistochemisty. RESULTS: The weights were reduced, the threshold of amygdala kindling and the stimulation number for full kindling decreased significantly, and seizures were more severe in the maternal isolation 3 hrs group compared with the normal control group. The expression of GABA(A) receptor alpha(1) in the hippocampus CA1 area in the maternal isolation 3 hrs group decreased significantly compared with that in the normal groups. There were no significant differences in the aspects above mentioned between the maternal isolation 15 min and normal control groups. CONCLUSIONS: The stress of early daily maternal isolation for 3 hrs may affect adversely brain development and increase epilepsy susceptibility in young rats. The decreased expression of GABA(A) receptor α1 in the hippocampus may contribute to the potential mechanism.