Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Movimento Celular , Neoplasias Pulmonares/metabolismo , MicroRNAs/metabolismo , Fatores de Transcrição SOXC/metabolismo , Células A549 , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , MicroRNAs/genética , Invasividade Neoplásica , Fatores de Transcrição SOXC/genética , Transdução de SinaisRESUMO
The present study aimed to explore the effects of histone deacetylase 6 (HDAC6) on brain injury in rats induced by apolipoprotein E4 (APOE4) and amyloid ß protein alloform 140 (Aß140) copolymerization. The rats were randomly divided into four groups: Control group, sham group, APOE4 + Aß140 coinjection group (model group) and HDAC6 inhibitor group (HDAC6 group). The brain injury model was established by coinjection of APOE4 + Aß140. Morris water maze experiment was used to observe the spatial memory and learning the ability of rats. Histological changes of the hippocampus were observed by hematoxylin and eosin staining. The mRNA expression levels of choline acetyltransferase (ChAT) and HDAC6 were detected by reverse transcriptionquantitative PCR. Immunohistochemistry was used to detect the protein expression of HDAC6. Western blotting was used to detect the protein expression levels of HDAC6, microtubuleassociated protein tau and glycogen synthase kinase 3ß (GSK3ß). APOE4 and Aß140 coaggregation decreased the shortterm spatial memory and learning ability of rats, whereas inhibition of HDAC6 activity attenuated the injury. Inhibition of HDAC6 activity resulted in an attenuation of the APOE4 and Aß140 coaggregationinduced increase in the number of dysplastic hippocampal cells. Further experiments demonstrated that APOE4 and Aß140 coaggregation decreased the expression levels of ChAT mRNA, and the phosphorylation levels of tau GSK3ß protein in the hippocampus, whereas inhibition of HDAC6 activity resulted in increased expression of ChAT mRNA, tau protein and GSK3ß phosphorylation. The inhibition of HDAC6 activity was also demonstrated to reduce brain injury induced by APOE4 and Aß140 coaggregation in model rats.
Assuntos
Peptídeos beta-Amiloides/metabolismo , Apolipoproteína E4/metabolismo , Lesões Encefálicas/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Hipocampo/metabolismo , Desacetilase 6 de Histona/biossíntese , Inibidores de Histona Desacetilases/farmacologia , Fragmentos de Peptídeos/metabolismo , Agregação Patológica de Proteínas/metabolismo , Animais , Lesões Encefálicas/patologia , Lesões Encefálicas/fisiopatologia , Colina O-Acetiltransferase/biossíntese , Hipocampo/patologia , Hipocampo/fisiopatologia , Desacetilase 6 de Histona/antagonistas & inibidores , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Agregação Patológica de Proteínas/patologia , Agregação Patológica de Proteínas/fisiopatologia , Ratos , Ratos Sprague-Dawley , Memória Espacial/efeitos dos fármacos , Proteínas tau/metabolismoRESUMO
OBJECTIVE: To determine the content of flavonoids and rutin in the different parts of Saussurea involucrata, and to establish their HPLC fingerprint chromatogram for the further development and utilization of the leaf. METHODS: The content of flavonoids was determined with UV. The similarity evaluation system for chromatographic fingerprint of TCM was used to calculate similar degree of the HPLC chromatogram of different parts. RESULTS: The content of flavonoids and rutin is relatively high in the leaf. The similarity between leaf and the whole grass is 0. 812.