RESUMO
Traditional Chinese medicine (TCM) has long been used to treat various diseases, including cerebral ischemia. The specific molecular mechanism of TCM in the treatment of cerebral ischemia, however, is still unclear. This study investigated the effects of gastrodin, electroacupuncture and their combination on cerebral ischemic rats. We used Nissl staining, immunohistochemical staining and immunoblotting to detect the expression changes of brain-derived neurotrophic factor (BDNF) and interleukin-6 (IL-6) in the frontal cortex. The results showed that the combination therapy of gastrodin and electroacupuncture significantly increased the number of Nissl-positive neurons and improved cell morphology compared with other groups. Mechanistically, we found that the combination of gastrodin and electroacupuncture treatment group can restore the abnormal morphology of neuronal cells caused by cerebral ischemia by rebalancing the expression levels of BDNF and IL-6. Our research indicates that gastrodin combined with electroacupuncture has a significant protective effect on cerebral ischemic injury in rats, possibly by regulating the expression of BDNF and IL-6. This combination therapy is superior to single-drug or electroacupuncture therapy.
Assuntos
Álcoois Benzílicos , Isquemia Encefálica , Fator Neurotrófico Derivado do Encéfalo , Modelos Animais de Doenças , Eletroacupuntura , Glucosídeos , Interleucina-6 , Ratos Sprague-Dawley , Animais , Eletroacupuntura/métodos , Álcoois Benzílicos/farmacologia , Glucosídeos/farmacologia , Glucosídeos/uso terapêutico , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Interleucina-6/metabolismo , Masculino , Isquemia Encefálica/metabolismo , Isquemia Encefálica/prevenção & controle , Ratos , Terapia Combinada/métodos , Acidente Vascular Cerebral/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismoRESUMO
OBJECTIVE: To investigate the effects of electroacupuncture(EA), gastrodin(Gas), and their combination on the signaling pathways involving Ras homologous gene family member A (RhoA) and Rho-associated frizzled helix protein kinase (ROCK-2) within the striatal region of rats subjected to cerebral ischemia. Additionally, we aim to elucidate the therapeutic effects and potential underlying mechanisms associated with the concurrent application of electroacupuncture and medication in the treatment of cerebral ischemia. METHODS: Rats were randomly assigned to one of five groups, namely, the sham operation (Sham) group, model group, EA group, Gas group, and the EA combined with Gas group (referred to as the "EA+Gas group"). Each group consisted of ten rats. Following the induction of cerebral ischemia, the EA group and EA+Gas group received EA stimulation at the Baihui(GV20) and Zusanli(ST36) acupoints for 30 min per session, administered once daily for 14 consecutive days. The Gas group and EA+Gas group were intraperitoneally injected with Gas at a dosage of 10 mg/kg, also administered once daily for 14 consecutive days. Nissl staining was employed to observe morphological alterations in the striatal nerve cells of rats in each group. Immunohistochemistry and western blot techniques were employed to evaluate the expression levels of striatal RhoA and ROCK-2 proteins. RESULTS: In comparison to the Sham group, the model group exhibited a substantial reduction in the number of striatal nerve cells on the ischemic side, accompanied by notable changes in cell morphology, characterized by reduced cytoplasm, defective and atrophied cytosol, solidified nuclei, loosely arranged cells, and enlarged intercellular spaces. Additionally, there was a notable increase in the positive expression of RhoA and ROCK-2. In contrast, when compared to the model group, the EA, Gas, and EA+Gas groups demonstrated an elevated number of normal nerve cells within the ischemic striatal region, with a significant improvement in cell count and morphology. Furthermore, positive expression levels of RhoA and ROCK-2 were notably reduced in these groups. Compared with the EA group or the GAS group, the number of normal nerve cells in the striatum on the ischemic side of the EA+GAS group was further increased, and the positive expression level of RhoA and ROCK-2 were both further reduced. CONCLUSION: The protective mechanism underlying the therapeutic efficacy of EA combined with Gas against cerebral ischemic striatal injury in rats may be associated with the inhibition of the activation of the RhoA/ROCK-2 signaling pathway. Importantly, the therapeutic effects observed with the combination of electroacupuncture and medication were superior to those achieved with EA alone or the sole administration of Gas.
Assuntos
Isquemia Encefálica , Eletroacupuntura , Animais , Ratos , Isquemia Encefálica/metabolismo , Infarto Cerebral , Transdução de SinaisRESUMO
OBJECTIVE: To investigate the potential mechanisms underlying the migration of endogenous neural stem cells (eNSCs) to the frontal cortex to differentiate into neurons, and to monitor the effect of electroacupuncture (EA) regulation of focal cerebral ischemia (FCI) in rats on the expression of growth arrest-specific protein 7 (Gas7) and nerve growth factor (NGF) in the prefrontal cortex (PFC). METHODS: Randomly, forty-eight male Sprague-Dawley rats were divided into four groups: Normal, Sham operation, Model, and EA. The right middle cerebral artery was embolized utilizing the thread-embolism technique. In the EA group, "Baihui" and "Zusanli" points were treated with electroacupuncture for 30 minutes, once a day, for 21 days. Nissl staining revealed the neuronal morphology of the PFC. Using immunohistochemistry and Western blot, the expression of Gas7 and NGF in the right PFC was observed. RESULTS: Nissl staining showed clear PFC neurons with centered nuclei and distinct nucleoli in the Normal and Sham groups. In the Model group, the PFC nuclei were distinctively smaller. The neuronal morphology in the EA group resembled that of the Normal group. Results from Western blot and immunohistochemistry were comparable. The expression of Gas7 and NGF in the Sham surgery group did not differ significantly from the Normal group. However, the expression of Gas7 and NGF in the Model group was significantly lower than in the Normal group. The expression of Gas7 and NGF was significantly higher in the EA group than in the Model group. CONCLUSIONS: EA can increase the expressions of Gas7 and NGF in the ischemic prefrontal cortex, which may be one of the mechanisms by which EA promotes the differentiation of eNSCs into neurons in the injured area.
Assuntos
Isquemia Encefálica , Eletroacupuntura , Ratos , Masculino , Animais , Ratos Sprague-Dawley , Fator de Crescimento Neural/metabolismo , Isquemia Encefálica/terapia , Isquemia Encefálica/metabolismo , Infarto Cerebral , Córtex Pré-Frontal/metabolismo , Proteínas do Tecido Nervoso/metabolismoRESUMO
OBJECTIVE: To observe the effect of electroacupuncture (EA) preconditioning on the expression of neuronal nitric oxide synthase (nNOS), inducible nitric synthase (iNOS) and glial fibrilliary acidic protein (GFAP) in the cortex of focal cerebral ischemia-reperfusion (CI/R) rats so as to explore its underlying mechanism in the protection of ischemic cerebral tissue. METHODS: Twenty-four Sprague-Dawley rats were randomized into sham operation (sham), model, and EA preconditioning groups (n = 8 in each group). The CI/R model was induced by intraluminal middle cerebral artery occlusion .(MCAO) with a nylon monofilament suture. Before modeling, EA (2 Hz/15 Hz, 3 V) was applied to "Baihui"(GV 20) and "Dazhui"(GV 14) for 30 min, once daily for 7 consecutive days. The neurologic impairment score was assessed by using Longa standards and the survival number of neurons in the local ischemic cerebral cortex was determined after Nissl staining, and the expression of nNOS, iNOS and GFAP in the cerebral cortex was detected using immunohistochemistry. RESULTS: Compared with the sham operation group, the neurological deficit score of the rats in the model group was significantly increased (P < 0.01), and the number of survival neurons of the ischemic cortex was obviously decreased (P < 0.01), and the expression levels of nNOS, iNOS and GFAP were significantly increased in the model group (P < 0.01). In the EA preconditioning group , the neurological deficit score, the expression levels of nNOS and iNOS were significantly down-regulated (P < 0.01), while the number of the survival neurons and GFAP expression level in the ischemic cerebral cortex were obviously higher in the EA preconditioning group in compared with the model group (P < 0.01). CONCLUSION: EA preconditioning can protect the ischemic cerebral cortex tissue from injury in CI/R rats, which may be related to its effects in down-regulating the expression of nNOS and iNOS, and up-regulating the expression of GFAP.
Assuntos
Isquemia Encefálica/genética , Isquemia Encefálica/terapia , Córtex Cerebral/metabolismo , Eletroacupuntura , Proteína Glial Fibrilar Ácida/genética , Óxido Nítrico Sintase/genética , Animais , Isquemia Encefálica/metabolismo , Isquemia Encefálica/cirurgia , Proteína Glial Fibrilar Ácida/metabolismo , Humanos , Masculino , Óxido Nítrico Sintase/metabolismo , Ratos , Ratos Sprague-Dawley , ReperfusãoRESUMO
OBJECTIVE: To observe the effects of electroacupuncture (EA) combined with Compound Salviae Miltiorrhizae Tablet (CSMT) on the expressions of brain derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) in hippocampus CA1 of chronic cerebral ischemia (CCI) rats. METHODS: Totally 50 Sprague-Dawley rats were randomly divided into the normal control group, the model group, the CSMT group, the EA group, and the EA +CSMT groups, 10 in each group. The CCI model was prepared by permanent bilateral common carotid arteries occlusion. One week after modeling, CSMT at 0.75 g/kg was given to rats in the EA + CSMT group and the CSMT group by gastrogavage, once daily, for 5 successive weeks. EA at Baihui (DU20) and Dazhui (DU14) was performed to rats in the EA group and the EA + CSMT group, lasting for 30 min, once daily, for 5 successive weeks. The expressions of BDNF and VEGF in the hippocampus CA1 area were detected by immunohistochemical assay and image analysis. RESULTS: Compared with the normal control group, the number of positively expressed BDNF and VEGF neurons and their expression intensity in the hippocampus CA1 of the model group obviously decreased (P < 0.01). Compared with the model group, the number of positively expressed BDNF and VEGF neurons and their expression intensity in the hippocampus CA1 of the CSMT group, the EA group, and the EA + CSMT groups obviously increased (P < 0.01, P < 0.05). The number of positively expressed BDNF and VEGF neurons and their expression intensity were obviously higher in the EA + CSMT group than those of the CSMT group and the EA group (P < 0.01). CONCLUSIONS: EA combined with CSMT could significantly increase the expressions of BDNF and VEGF in the hippocampus CA1 of CCl rats. Besides, their effects were significantly higher than those of the CSMT group or the EA group.
Assuntos
Isquemia Encefálica/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Região CA1 Hipocampal/metabolismo , Eletroacupuntura , Salvia miltiorrhiza , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Isquemia Encefálica/terapia , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND & OBJECTIVE: Urothelial carcinoma of the urinary bladder is a common malignant neoplasm of the genitourinary system. This study was to analyze chromosome aberrations in urothelial carcinoma of the urinary bladder in Chinese, and evaluate the possibility and validity of multicolor fluorescence in situ hybridization (M-FISH) in detecting urothelial carcinoma of the urinary bladder. METHODS: The probes of chromosome 3, 7, 17 centromeres and 9p21 region were labeled by random primer method. M-FISH was performed on interphase nuclei of 57 samples of urothelial carcinoma to analyze the correlations of chromosome aberration to diagnosis and pathology of urothelial carcinoma. RESULTS: The rate of aneuploidy was 47.4% for chromosome 3, 50.9% for chromosome 7, 56.1% for chromosome 17, and 59.6% for chromosome 9p21 in urothelial carcinoma. All the aberrations had no correlations to tumor stage. The aberrations of chromosomes 3, 7, 17 were significantly correlated to pathologic grade (P<0.01). As using the 4 chromosome probes in combination, the sensitivity for detecting urothelial carcinoma of the urinary bladder was 54.4%. CONCLUSION: M-FISH may be helpful for detecting urothelial carcinoma of the urinary bladder.