Metabolic memory means if the hyperglycemia can't be controlled at early stage of diabetes, chronic complications such as diabetic retinopathy (DR) will continue to develop even if the blood glucose level maintains normal level at later stage. Oxidative stress plays an important role in the "metabolic memory" of DR, which interacts with the nitrative stress, advanced glycation end products, genetic modification and endoplasmic reticulum stress in the pathogenesis of DR. Further elucidation of the relationship between oxidative stress and "metabolic memory" of DR can open the way for the discovery of novel therapeutic targets to prevent DR progression.
ObjectiveTo investigate the influence of Ataxia-telangiectasia mutated (ATM) activation on cellular oxidative stress induced by high glucose in bovine retinal capillary endothelial cells(BRECs). Methods The BRECs were treated by different culture medium with various glucose concentrations (5 mmol/L glucose, 30 mmol/L glucose, 30 mmol/L glucose+10 μmol/L KU55933) as normal glucose group, high glucose group and treatment group respectively.After the cells incubated for 48 hours, the protein expression of ATM, P-ATM, Mitogen-Activated Protein Kinase P38(P38), P-P38, Extracellular signal-regulated kinases(ERKs), P-ERKs was detected by Western blot; cellular ROS level was detected by Reactive Oxygen Species Assay Kit; propidium iodide/Hoechst staining was used for analysis of apoptosis; the expression of vascular endothelial growth factor (VEGF) in the supernatant was determined by Enzyme-Linked Immunosorbent Assay (ELISA); the paracellular permeability between endothelium cells was detected by FITC-dextran. ResultsCompared with the protein level of P-ATM, P-P38 and P-ERKs in high glucose group increased. Especially, P-P38, P-ERKs expressed much more than in high glucose group. The secretion of VEGF in high glucose group was higher than that in the normal glucose group but less than that in treatment group. The same tendency existed in ROS assay, apoptosis assay and paracellular permeability measuring. ConclusionsHigh glucose induced altered activation of ATM which might play a protective role in cellular oxidative stress. Deficiency of ATM might lead to ROS explosion, cell apoptosis and dysfunction of endothelial barrier. The mechanism might be associated with P38, ERKs and VEGF.
ObjectiveTo evaluate laparoscopic anti-reflux surgery for treatment of chronic obstructive pulmonary disease (COPD) associated with gastroesophageal reflux disease (GERD).MethodsA total of 20 patients with GERD and COPD underwent laparoscopic anti-reflux procedure in the First Affiliated Hospital of Zhengzhou University from January 2016 to December 2017. The reflux diagnostic questionnaire, pulmonary function, COPD assessment test scale, 24-hour esophageal pH-impedance monitoring and esophageal pressure measurement were performed in all patients. All drug-refractory patients underwent the laparoscopic anti-reflux surgery. After 12 months follow-up, the parameters of COPD and GERD were evaluated again.ResultsTwenty patients with COPD and GERD were successfully performed laparoscopic anti-reflux surgery, no hernia patch repair patient and death patient occurred. There was no esophageal rupture, bleeding, infection, and other serious postoperative complications. Although 8 patients had the different degree dysphagia and 10 patients had the different degree abdominal distention, they all relieved themselves. Twenty patients with GERD and COPD were followed up for 1 year. Compared with the values before treatment, the GERD symptom score, reflux times, DeMeester score, and COPD assessment test score of the patients were significantly reduced (P<0.05), the lower esophageal sphincter pressure, percentage of forced expiratory volume in one second (FEV1) in the predicted value and FEV1/forced vital capacity (FVC) were significantly increased (P<0.05) after the treatment. According to the grading standard of The Global Initiative for Chronic Obstructive Lung Disease (GOLD), 5 cases of grade Ⅰ, 2 cases of grade Ⅱ and 1 case of grade Ⅲ were cured; 1 case of grade Ⅰ, 4 cases of grade Ⅱ and 4 cases of grade Ⅲ were improved; 1 case of grade Ⅰ, 1 case of grade Ⅱ and 1 case of grade Ⅳ were ineffective. The total effective rate was 85% (17/20).ConclusionsCOPD is closely related to GERD. Laparoscopic anti-reflux surgery can not only effectively treat GERD, but also markedly improve COPD.