RESUMO
OBJECTIVE: The aim of this study was to compare the clinical efficacy of the full-endoscopic posterior cervical foraminotomy (FE-PCF) and the unilateral biportal endoscopic posterior cervical foraminotomy (UBE-PCF) in the treatment of cervical spondylotic radiculopathy (CSR). METHODS: Patients who underwent posterior cervical spine surgery in our hospital from January 2020 to December 2022 were retrospectively analyzed. According to the surgical method, the patients were divided into two groups: FE-PCF group and UBE-PCF group. Perioperative data included operation time, Intraoperative blood loss and postoperative hospital stay were collected. The Visual Analog Scale (VAS)-arm, VAS-neck, and Neck Diability Index (NDI) was used to evaluate the clinical outcomes at preoperative, postoperative 1 week and Last follow-up. Serum creatine phosphokinase (CPK) and C-reactive protein (CRP) levels were recorded to evaluate surgical invasiveness. RESULTS: A total of 160 patients were included, including 89 cases of FE-PCF and 71 cases of UBE-PCF. The demographic and preoperative data showed no significant differences between the two groups (P > 0.05). The mean operating time was significantly shorter in the UBE-PCF group compared to FE-PCF group (P < 0.05). Serum CRP and CPK levels of the two groups both exhibited a pattern of rising and then falling, peaking one day following surgery and decreasing to near normal values three days after the operation. Compared with preoperative, both groups showed significant improvement in postoperative VAS and NDI scores, with a statistically significant difference (P < 0.05). However, the differences in results between the groups were not significant. CONCLUSIONS: Both UBE-PCF and FE-PCF are secure and efficient methods for treating CSR by continuous visualization. UBE-PCF offers predictable and adequate decompression within a reduced surgical duration, facilitated by its separate observation and operation channels.
Assuntos
Vértebras Cervicais , Foraminotomia , Radiculopatia , Espondilose , Humanos , Masculino , Feminino , Radiculopatia/cirurgia , Pessoa de Meia-Idade , Espondilose/cirurgia , Estudos Retrospectivos , Foraminotomia/métodos , Adulto , Resultado do Tratamento , Vértebras Cervicais/cirurgia , Idoso , Endoscopia/métodos , Neuroendoscopia/métodosRESUMO
BACKGROUND: Unilateral laminotomy for bilateral decompression (ULBD) has yielded positive results in the treatment of lumbar spinal stenosis (LSS). Unilateral biportal ULBD (UB-ULBD) and percutaneous endoscopic ULBD (PE-ULBD) are gaining popularity because of the progress that has been made in minimally invasive surgery (MIS). The objective of this study was to evaluate and compare the radiographic and clinical results of UB-ULBD and PE-ULBD. METHODS: This study retrospectively enrolled patients who underwent ULBD surgery for LSS. The patients were categorized into two groups on the basis of the surgical method: the UB-ULBD group and the PE-ULBD group. Data on the general demographic data, surgical details, clinical efficacy, radiography and complications were compared between the two groups were compared. The minimum follow-up duration was 12 months. RESULTS: A total of 113 LSS patients who had undergone ULBD at our institution were included, of whom 61 patients underwent UB-ULBD surgery and 52 underwent PE-ULBD surgery. The UB-ULBD group had a significantly shorter operation time (P < 0.05). The facet was significantly better preserved in the UB-ULBD group than in the PE-ULBD group, and the angle of ipsilateral facet joint resection in the UE-ULBD group was significantly smaller (P < 0.05). The ODI score, VAS score and modified Macnab criteria improved postoperatively in both groups. The UB-ULBD group had a 95.08% rate of excellent or good patient outcomes, whereas the PE-ULBD group had a 92.30% rate. CONCLUSION: Both UB-ULBD and PE-ULBD can provide favourable clinical outcomes when used to treat LSS. UB-ULBD is beneficial because of its shorter operation time, smaller angle of ipsilateral facet joint resection and better facet preservation, making it a viable and safe option for treating LSS while ensuring spinal stability.
Assuntos
Descompressão Cirúrgica , Endoscopia , Laminectomia , Vértebras Lombares , Estenose Espinal , Humanos , Estenose Espinal/cirurgia , Estenose Espinal/diagnóstico por imagem , Feminino , Masculino , Estudos Retrospectivos , Descompressão Cirúrgica/métodos , Laminectomia/métodos , Pessoa de Meia-Idade , Idoso , Vértebras Lombares/cirurgia , Vértebras Lombares/diagnóstico por imagem , Resultado do Tratamento , Endoscopia/métodos , Seguimentos , Duração da CirurgiaRESUMO
PURPOSE: To compare the clinical efficacy of mini-open (air/water medium) endoscopy-assisted anterior cervical discectomy and fusion (MOEA-ACDF) and anterior cervical decompression and fusion (ACDF) for cervical spondylotic myelopathy (CSM). METHODS: This study retrospectively analysed the clinical data of CSM patients who received surgical treatment from January 1, 2020, to December 31, 2022. Patients were divided into two groups according to the surgical method: the MOEA-ACDF group and the ACDF group. The preoperative and postoperative imaging results at one week and the last follow-up examination were compared between the two groups. The Japanese Orthopaedic Association (JOA) score, visual analogue scale (VAS) score and neck disability index (NDI) score were used to evaluate the clinical outcomes preoperatively, one week postoperatively and at the last follow-up examination. The minimum follow-up duration was 12 months. RESULTS: A total of 131 CSM patients who underwent surgery at our institution were included, including 61 patients in the MOEA-ACDF group and 70 patients in the ACDF group. In the MOEA-ACDF group, the postoperative C2-C7 Cobb angle and HAVB were significantly greater than the preoperative values (P < 0.05). In the ACDF group, the postoperative C2-C7 Cobb angle was also significantly greater than the preoperative value, and the C2-C7 ROM and HAVB significantly decreased (P < 0.05). The postoperative neurological function of the patients in both groups improved, and the postoperative VAS score and NDI score significantly decreased. Compared with ACDF, MOEA-ACDF is associated with a significantly larger postoperative C2-C7 Cobb angle and significantly better C2-C7 ROM and HAVB, as well as better clinical efficacy (P < 0.05). CONCLUSIONS: MOEA-ACDF combines endoscopic systems with ACDF technology to treat CSM, but its clinical efficacy is not inferior to that of ACDF in the short- to intermediate-term. It can effectively and safely restore the cervical intervertebral height, physiological curvature, and range of motion.
Assuntos
Vértebras Cervicais , Discotomia , Endoscopia , Fusão Vertebral , Espondilose , Humanos , Masculino , Fusão Vertebral/métodos , Fusão Vertebral/efeitos adversos , Feminino , Pessoa de Meia-Idade , Vértebras Cervicais/cirurgia , Vértebras Cervicais/diagnóstico por imagem , Estudos Retrospectivos , Discotomia/métodos , Discotomia/efeitos adversos , Espondilose/cirurgia , Espondilose/diagnóstico por imagem , Endoscopia/métodos , Resultado do Tratamento , Idoso , Descompressão Cirúrgica/métodos , Descompressão Cirúrgica/efeitos adversos , Adulto , Doenças da Medula Espinal/cirurgia , Doenças da Medula Espinal/diagnóstico por imagemRESUMO
This study combined with bioinformatics analysis and investigated the expression pattern of miR-181b-5p, as well as explored its role and mechanism in cholangiocarcinoma (CCA or CHOL). Several bioinformatics databases were used to analyze the expression of miR-181b and the enrichment of miR-181b in biological activities and biological pathways in CCA. The RT-qPCR analysis was used to examine the expression levels of miR-181b-5p. A receiver operation characteristics (ROC) curve analysis and the Kaplan-Meier survival assay were conducted to validate the diagnostic and prognostic implication of miR-181b-5p. Cell experiments were used to explore the possible functional role of miR-181b-5p in CCA progression. The bioinformatics assay was used to predict the target gene of miR-181b-5p and Western blot was used to confirm the related signaling pathway. The bioinformatics analysis results suggest that miR-181b-5p was highly expressed in cholangiocarcinoma and its expression was negatively related to PARK2 expression in CCA tissues. miR-181b-5p expression in the serum and tissues was upregulated and associated with lymph node metastasis and TNM stage. Increased expression of miR-181b-5p had relatively high diagnostic accuracy and showed poor prognosis in CCA patients. In addition, miR-181b-5p overexpression enhanced cell proliferation, migration, and invasion by targeting PARK2. Overexpression of miR-181b-5p activated the PI3K/AKT signaling pathway, while knockdown of miR-181b-5p suppressed the signaling pathway. Increased expression of miR-181b-5p in CCA may be a potential diagnostic or/and prognostic indicator for CCA patients. The present data indicated miR-181b-5p acted as an oncogene in CCA through promoting tumor cell proliferation, migration, and invasion of CCA via the PTEN/PI3K/AKT signaling pathway by targeting PARK2, which might be a promising therapeutic target or biomarker for CCA.
Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , MicroRNAs , Ubiquitina-Proteína Ligases/genética , Neoplasias dos Ductos Biliares/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Colangiocarcinoma/genética , Humanos , MicroRNAs/genética , PTEN Fosfo-Hidrolase/genética , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de SinaisRESUMO
PURPOSE: Ossification of ligamentum flavum (OLF) is the leading cause of progressive thoracic myelopathy (TM) in East Asian countries. Surgical decompression is the general treatment for TM. This study investigated the application of percutaneous full endoscopic posterior decompression (PEPD) for the treatment of thoracic OLF. METHODS: Eighteen patients with TM were treated by PEPD under local anaesthesia. Patients had an average age of 59.1 years and single-level lesions mostly at the lower thoracic vertebrae. Computed tomography and magnetic resonance imaging were used to classify the OLF. The pre- and postoperative neurological statuses were evaluated using the American Spinal Injury Association (ASIA) sensory and motor score, modified Japanese Orthopaedic Association (mJOA) score and Frankel grade. RESULTS: OLF for all patients was classed as lateral, extended, and enlarged types without comma and tram track signs. Decompression was completed, and a dome-shaped laminotomy was performed through limited laminectomy and flavectomy. Dural tears in 2 patients were the only observed complication. The average score of ASIA sensory and motor, mJOA, as well as the Frankel grade improved significantly after surgery at an average follow-up time of 17.4 months. The average recovery rate (RR) was 47.5% as calculated from the mJOA scores. According to RR, 10 cases were classified as good, 4 cases fair, and 4 cases unchanged. CONCLUSIONS: For patients with thoracic OLF at a single level and lateral, extended, and enlarged types without comma and tram track signs, it is safe and reliable to perform PEPD, which has satisfactory clinical results. These slides can be retrieved under Electronic Supplementary Material.
Assuntos
Descompressão Cirúrgica/métodos , Endoscopia/métodos , Doenças da Medula Espinal/cirurgia , Doenças da Coluna Vertebral/cirurgia , Vértebras Torácicas/cirurgia , Humanos , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Background: The challenge in treating irreversible nerve tissue damage has resulted in suboptimal outcomes for spinal cord injuries (SCI), underscoring the critical need for innovative treatment strategies to offer hope to patients. Methods: In this study, gelatin methacrylic acid hydrogel scaffolds loaded with nerve growth factors (GMNF) were prepared and used to verify the performance of SCI. The physicochemical and biological properties of the GMNF were tested. The effect of GMNF on activity of neuronal progenitor cells (NPCs) was investigated in vitro. Histological staining and motor ability was carried out to assess the ability of SCI repair in SCI animal models. Results: Achieving nerve growth factors sustained release, GMNF had good biocompatibility and could effectively penetrate into the cells with good targeting permeability. GMNF could better enhance the activity of NPCs and promote their directional differentiation into mature neuronal cells in vitro, which could exert a good neural repair function. In vivo, SCI mice treated with GMNF recovered their motor abilities more effectively and showed better wound healing by macroscopic observation of the coronal surface of their SCI area. Meanwhile, the immunohistochemistry demonstrated that the GMNF scaffolds effectively promoted SCI repair by better promoting the colonization and proliferation of neural stem cells (NSCs) in the SCI region and targeted differentiation into mature neurons. Conclusion: The application of GMNF composite scaffolds shows great potential in SCI treatment, which are anticipated to be a potential therapeutic bioactive material for clinical application in repairing SCI in the future.
Assuntos
Diferenciação Celular , Proliferação de Células , Gelatina , Hidrogéis , Metacrilatos , Células-Tronco Neurais , Traumatismos da Medula Espinal , Animais , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/citologia , Traumatismos da Medula Espinal/terapia , Traumatismos da Medula Espinal/tratamento farmacológico , Gelatina/química , Hidrogéis/química , Hidrogéis/farmacologia , Diferenciação Celular/efeitos dos fármacos , Camundongos , Proliferação de Células/efeitos dos fármacos , Metacrilatos/química , Alicerces Teciduais/química , Regeneração Nervosa/efeitos dos fármacos , Fator de Crescimento Neural/farmacologia , Modelos Animais de DoençasRESUMO
Objective: To investigate the safety and effectiveness of unilateral biportal endoscopy (UBE) technique in the treatment of single-segment thoracic ossification of ligamentum flavum (TOLF). Methods: Between August 2020 and December 2021, 11 patients with single-segment TOLF were treated with UBE technique. There were 6 males and 5 females, with an average of 58.2 years (range, 49-72 years). The responsible segment was T 6, 7 in 1 case, T 7, 8 in 1 case, T 8, 9 in 2 cases, T 9, 10 in 2 cases, T 10, 11 in 2 cases, and T 11, 12 in 3 cases. Imaging examination showed that the ossification were located on the left side in 4 cases, on the right side in 3 cases, and on bilateral sides in 4 cases. The main clinical symptoms were chest and back pain or lower limb pain, all accompanied by lower limb numbness and fatigue. The disease duration ranged from 2 to 28 months (median, 17 months). The operation time, postoperative hospital stay, and complications were recorded. Visual analogue scale (VAS) score was used to evaluate the chest and back pain and low limb pain, and Oswestry disability index (ODI) and Japanese Orthopedic Association (JOA) score were used to evaluate functional recovery before operation and at 3 days, 1 month, 3 months after operation, and last follow-up. The anteroposterior diameter of the coronal spinal canal was measured by CT before and after operation to evaluate the effect of surgical decompression. Results: All operations were successfully completed. The operation time was 50-105 minutes, with an average of 80.0 minutes. No postoperative complication such as dural sac tear, cerebrospinal fluid leakage, spinal nerve injury, or infection occurred. The postoperative hospital stay was 2-5 days, with an average of 3.1 days. All incisions healed by first intention. All patients were followed up 6-22 months, with an average of 14.8 months. CT measurement at 3 days after operation showed that the anteroposterior diameter of the spinal canal was (8.63±1.61) mm, which was significantly larger than that before operation [(3.67±1.37) mm] ( t=-12.181, P<0.001). The VAS score of chest and back pain and lower limb pain and ODI at each time point after operation were significantly lower than those before operation ( P<0.05). The above indexes were further improved after operation, except that there was no significant difference between at 3 months after operation and at last follow-up ( P>0.05), the differences between other time points were significant ( P<0.05). There was no recurrence during the follow-up period. Conclusion: UBE technique is a safe and effective method to treat single-segment TOLF, but its long-term effectiveness needs to be further studied.
Assuntos
Ligamento Amarelo , Estenose Espinal , Masculino , Feminino , Humanos , Estenose Espinal/cirurgia , Osteogênese , Ligamento Amarelo/cirurgia , Endoscopia , Estudos Retrospectivos , Dor , Resultado do Tratamento , Vértebras LombaresRESUMO
OBJECTIVE: To investigate the methods and clinical significance of detecting PLAC4 and COL6A1 gene on fetal chromosome 21 from maternal peripheral blood. METHODS: From Oct. 2008 to Nov. 2009 30 normal pregnancies in Weifang People's Hospital were selected as pregnant group, and 9 non-pregnant women were selected as control group. Quantitative real-time PCR was used to determine transcript levels of the target genes (PLAC4 and COL6A1) in blood samples. Correlation between the expression level and gestational age was analyzed. RESULTS: (1) PLAC4 mRNA was detected in peripheral blood of all pregnant women. Its maximum level was 12.760×10(3) copies/ml, whereas the minimum was 2.105×10(3) copies/ml, and the average value is 6.612×10(3) copies/ml. In control group the PLAC4 mRNA could not be detected. There was statistically significant difference (P < 0.01) between the two groups. (2) COL6A1 mRNA is detected in pregnant group and control group, and the concentration was 6.847×10(3) copies/ml and 7.322×10(3) copies/ml respectively, with no statistically significant difference (P > 0.05). (3) Correlation analysis: there was no relationship between the level of PLAC4, COL6A1 mRNA and the gestational age, the correlation coefficients (r) were 0.29 and 0.31, and the P values were 0.121 and 0.168 respectively. CONCLUSIONS: COL6A1 mRNA can be detected in both pregnant group and control group, so it is not specific for pregnancy. PLAC4 mRNA can be detected only in pregnant women, so it has specificity in pregnancy and can be a discriminative marker gene for prenatal diagnosis of trisomy 21 fetuses.
Assuntos
Colágeno Tipo VI/sangue , Síndrome de Down/diagnóstico , Proteínas da Gravidez/sangue , Diagnóstico Pré-Natal/métodos , RNA Mensageiro/sangue , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Colágeno Tipo VI/genética , Citogenética , Síndrome de Down/sangue , Feminino , Humanos , Reação em Cadeia da Polimerase/métodos , Gravidez , Proteínas da Gravidez/genética , RNA Mensageiro/genéticaRESUMO
Minimally invasive surgery (MIS) has shown satisfactory surgical results for the treatment of thoracic myelopathy (TM) caused by ossification of the ligamentum flavum (OLF). This study investigated the prognostic factors following MIS and was based on the retrospective analysis of OLF patients who underwent percutaneous full endoscopic posterior decompression (PEPD). Thirty single-segment OLF patients with an average age of 60.4 years were treated with PEPD under local anaesthesia. Clinical data were collected from the medical and operative records. The surgical results were assessed by the recovery rate (RR) calculated from the modified Japanese Orthopaedic Association (mJOA) score. Correlations between the RR and various factors were analysed. Patients' neurological status improved from a preoperative mJOA score of 6.0 ± 1.3 to a postoperative mJOA score of 8.5 ± 2.0 (P < 0.001) at an average follow-up of 21.3 months. The average RR was 53.8%. Dural tears in two patients (6.7%, 2/30) were the only observed complications. Multiple linear regression analysis showed that a longer duration of preoperative symptoms and the presence of a high intramedullary signal on T2-weighted MRI (T2HIS) were significantly associated with poor surgical results. PEPD is feasible for the treatment of TM patients with a particular type of OLF. Patients without T2HIS could achieve a good recovery if they received PEPD early.
Assuntos
Descompressão Cirúrgica , Ligamento Amarelo/patologia , Neuroendoscopia , Ossificação Heterotópica/complicações , Ossificação Heterotópica/patologia , Compressão da Medula Espinal/etiologia , Compressão da Medula Espinal/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Descompressão Cirúrgica/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Neuroendoscopia/métodos , Prognóstico , Compressão da Medula Espinal/diagnóstico , Cirurgia Assistida por Computador , Tomografia Computadorizada por Raios XAssuntos
Endoscopia , Vértebras Lombares , Fusão Vertebral , Espondilolistese , Humanos , Espondilolistese/cirurgia , Espondilolistese/diagnóstico por imagem , Vértebras Lombares/cirurgia , Vértebras Lombares/diagnóstico por imagem , Fusão Vertebral/métodos , Endoscopia/métodos , Masculino , Resultado do Tratamento , Pessoa de Meia-Idade , FemininoRESUMO
The paper presents theoretical results on the global asymptotic stability and synchronization of a class of fractional-order memristor-based neural networks (FMNN) with multiple delays. First, the asymptotic stability of fractional-order (FO) linear systems with single or multiple delays is discussed. Delay-independent stability criteria for the two types of systems are established by using the maximum modulus principle and the spectral radii of matrices. Second, new testable algebraic criteria for ensuring the existence and global asymptotic stability of the system equilibrium point are obtained by employing the Kakutani's fixed point theorem of set-valued maps, the comparison theorem, and the stability criterion for FO linear systems with multiple delays. Third, the synchronization criterion for FMNN is presented based on the linear error feedback control. Finally, numerical examples are given demonstrating the effectiveness of the proposed results.
Assuntos
Aprendizado de Máquina , Redes Neurais de Computação , RetroalimentaçãoRESUMO
Liver ischemia and reperfusion (I/R) injury is characterized by defective liver autophagy accompanied by alterations to the endogenous defense system. Dihydromyricetin (DHM) is a natural flavonoid that demonstrates a wide range of physiological functions, and has been implicated as a regulator of autophagy. This study investigates the protective effects of DHM pretreatment on liver injury caused by ischemia/reperfusion (I/R) and elucidates the potential mechanism of DHM-mediated protection. Mice were subjected to 60 minutes of ischemia followed by 5 hours of reperfusion. DHM (100 mg/kg bw/day) or the vehicle was administered daily by gavage 7 days before ischemia and immediately before reperfusion. In this study, DHM markedly decreased serum aminotransferase activity and inhibited liver I/R -stimulated apoptosis. Moreover, DHM exerted hepatoprotective effects by upregulating mRNA levels of various essential autophagy-related genes including ATG5, ATG12, BECN1, and LC3. Autophagy inhibitor chloroquine or Atg5 knockdown blocked DHM -mediated elevation in liver function. Specifically, DHM significantly increased FOXO3a expression, and enhanced FOXO3a nuclear translocation and Ser588 phosphorylation modification. Importantly, the inhibition of FOXO3a with FOXO3a-siRNA in mice decreased DHM-induced autophagy-related genes and diminished the protective effects of DHM against liver I/R injury. In summary, these findings identify DHM as a novel hepatoprotective small molecule by elevating FOXO3a expression and nuclear translocation, stimulating autophagy-related genes and suppressing liver I/R-induced apoptosis, suggesting FOXO3a may have therapeutic value in liver cell protection in liver I/R injury.
Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Flavonóis/farmacologia , Proteína Forkhead Box O3/genética , Hepatopatias/metabolismo , Substâncias Protetoras/farmacologia , Traumatismo por Reperfusão/metabolismo , Animais , Caspase 3/metabolismo , Modelos Animais de Doenças , Proteína Forkhead Box O3/metabolismo , Hepatopatias/tratamento farmacológico , Hepatopatias/patologia , Camundongos , Camundongos Endogâmicos C57BL , Fosforilação , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/patologiaRESUMO
Both melamine and cyanuric acid have low toxicity, but together they may cause serious lesions to the kidney, via an unknown mechanism. This study was aimed to estimate whether lesions to the kidney were relative to oxidative damage and hypoxia in the kidney after mice exposed to 1mg/kg/day, 5mg/kg/day or 25mg/kg/day of a mixture of melamine and cyanuric acid for 13 weeks. Pathological changes to the kidneys, oxidative stress and energy parameters and hypoxia-inducible factor-1α (HIF-1α) change in the kidneys were evaluated. Pathological changes were found in the distal tubules of kidneys, such as crystals, proteinaceous casts and compensatory expansion, indicating that the mixture induced toxicity to the kidney. The activities of total antioxidant capacity (TAC) and superoxide dismutase (SOD) and the concentration of glutathione (GSH) decreased, while the concentrations of lipid peroxidation (MDA) and protein carbonyl groups (PC) increased after exposure to the mixture, demonstrating that the mixture resulted in imbalance of antioxidant and reactive oxygen species (ROS) and excessive ROS induced oxidant damage to lipid and proteins in kidneys. The activities of malate dehydrogenase (MDH) and succinate dehyrogenase (SDH) decreased, however, the activity of lactic dehydrogenase (LDH) and the concentration of HIF-1α increased after exposure to the mixture. Accordingly, it was concluded that the mixture resulted in a hypoxic state in kidneys and that both oxidative stress and hypoxia contributed to the lesion of kidneys. The exact cause of oxidative damage and hypoxia is not clear, it might be caused by either a direct effect or by an indirect effect, which is secondary to substantial renal damage caused by tubular obstruction due to crystal formation.
Assuntos
Hipóxia/induzido quimicamente , Rim/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Triazinas/efeitos adversos , Administração Oral , Animais , Relação Dose-Resposta a Droga , Glutationa/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Rim/química , Rim/patologia , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Superóxido Dismutase/metabolismo , Triazinas/administração & dosagemRESUMO
Mitochondrial impairment is hypothesized to contribute to the pathogenesis of chronic cholestatic liver diseases. Mitofusin 2 (Mfn2) regulates mitochondrial morphology and signaling and is involved in the development of numerous mitochondrial-related diseases; however, a functional role for Mfn2 in chronic liver cholestasis which is characterized by increased levels of toxic bile acids remain unknown. Therefore, the aims of this study were to evaluate the expression levels of Mfn2 in liver samples from patients with extrahepatic cholestasis and to investigate the role Mfn2 during bile acid induced injury in vitro. Endogenous Mfn2 expression decreased in patients with extrahepatic cholestasis. Glycochenodeoxycholic acid (GCDCA) is the main toxic component of bile acid in patients with extrahepatic cholestasis. In human normal hepatocyte cells (L02), Mfn2 plays an important role in GCDCA-induced mitochondrial damage and changes in mitochondrial morphology. In line with the mitochondrial dysfunction, the expression of Mfn2 decreased significantly under GCDCA treatment conditions. Moreover, the overexpression of Mfn2 effectively attenuated mitochondrial fragmentation and reversed the mitochondrial damage observed in GCDCA-treated L02 cells. Notably, a truncated Mfn2 mutant that lacked the normal C-terminal domain lost the capacity to induce mitochondrial fusion. Increasing the expression of truncated Mfn2 also had a protective effect against the hepatotoxicity of GCDCA. Taken together, these findings indicate that the loss of Mfn2 may play a crucial role the pathogenesis of the liver damage that is observed in patients with extrahepatic cholestasis. The findings also indicate that Mfn2 may directly regulate mitochondrial metabolism independently of its primary fusion function. Therapeutic approaches that target Mfn2 may have protective effects against hepatotoxic of bile acids during cholestasis.