Metformin alleviates chronic obstructive pulmonary disease and cigarette smoke extract-induced glucocorticoid resistance by activating the nuclear factor E2-related factor 2/heme oxygenase-1 signaling pathway

Chronic obstructive pulmonary disease (COPD) is an important healthcare problem worldwide. Often, glucocorticoid (GC) resistance develops during COPD treatment. As a classic hypoglycemic drug, metformin (MET) can be used as a treatment strategy for COPD due to its anti-inflammatory and antioxidant effects, but its specific mechanism of action is not known. We aimed to clarify the role of MET on COPD and cigarette smoke extract (CSE)-induced GC resistance. Through establishment of a COPD model in rats, we found that MET could improve lung function, reduce pathological injury, as well as reduce the level of inflammation and oxidative stress in COPD, and upregulate expression of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), multidrug resistance protein 1 (MRP1), and histone deacetylase 2 (HDAC2). By establishing a model of GC resistance in human bronchial epithelial cells stimulated by CSE, we found that MET reduced secretion of interleukin-8, and could upregulate expression of Nrf2, HO-1, MRP1, and HDAC2. MET could also increase the inhibition of MRP1 efflux by MK571 significantly, and increase expression of HDAC2 mRNA and protein. In conclusion, MET may upregulate MRP1 expression by activating the Nrf2/HO-1 signaling pathway, and then regulate expression of HDAC2 protein to reduce GC resistance.

Huatanjiangqi capsule regulates Nrf2/HDAC2 and improves glucocorticoid resistance of 16HBE cells / 中国临床药理学与治疗学

AIM: To explore the effect of Huatanjiangqi capsule medicated serum (HTJQ) on the resistance of human bronchial epithelial cells (16HBE) to glucocorticoid (GC) stimulated by cigarette smoke extract (CSE). METHODS: After 16HBE cells were treated with HTJQ, the effects of different concentrations of HTJQ on the viability of 16HBE cells were determined by CCK-8 method. 16HBE cells were pretreated with HTJQ, and then cultured with dexamethasone (DEX) and lipopolysaccharide (LPS) for 24 hours, the effect of HTJQ on glucocorticoid (GC) resistance of 16HBE cells was determined by Enzyme-linked immunosorbent assay (ELISA). The effects of HTJQ, sulforaphane (SFN) and glutathione (GSH) on the expression of NF-E2-related factors 2 (Nrf2), Heme oxygenase-1 (HO-1) and histone deacetylase 2 (HDAC2) in 16HBE cells stimulated by CSE were measured by Western blot, and the effects of HTJQ, SFN and GSH on interleukin-8 (IL-8) in 16HBE cells were measured by ELISA. RESULTS: HTJQ promoted the proliferation of 16HBE cells at 1 h, 2 h and 4 h, the results of ELISA and Western blot showed that CSE induced GC resistance and decreased the expression of Nrf2, HO-1 and HDAC2 in 16HBE cells, HTJQ significantly decreased IL-8 and improved GC sensitivity of 16HBE cells (P<0.01), and up-regulated the expression of Nrf2, HO-1 and HDAC2 (P<0.01). In addition, HTJQ significantly up-regulated the level of GSH in 16HBE cells (P<0.01). Nrf2 agonists SFN and GSH significantly improved the glucocorticoid sensitivity of 16HBE cells (P<0.01), and up-regulated the expression of Nrf2, HO-1 and HDAC2 (P<0.01). CONCLUSION: HTJQ improves the GC resistance of 16HBE cells by up-regulating the expression of Nrf2/HDAC2 protein and the level of intracellular GSH.

Animal study on master-slave system controlled robot-assisted flexible endoscopy in gastricendoscopy examination / 中华消化杂志

Objective@#To evaluate the safety, feasibility and operational effectiveness of master-slave system controlled Robot-assisted flexible endoscopy 'YunSRobot’ in upper gastrointestinal endoscopy examination in living pigs. @*Methods@#Seven Guangxi BA-MA Mini-pigs underwent upper gastrointestinal endoscopy examination with master-slave system controlled Robot-assisted flexible endoscopy 'YunSRobot’ and Olympus GIF-Q260J gastroendoscope (Japan). The experiment divided into manual operation group and robot operation group. Nine gastroenterologists skilled with endoscopy operation handled the robot once in vitro to familiar with the mechanism and method of robot operation. And then performed manual operation and robot operation four times each. Endoscopy pictures and operation time were recorded. T test and one-way analysis of variance were performed for statistical analysis. @*Results@#Both manual operation and robot operation could successfully finish standard esophagus and stomach endoscopic examination. There were no complications such as hemorrhage, perforation, mistaken insertion into of trachea, injures of pharynx and larynx and inhalation pneumonia. Esophagus, gastric cardia, gastric fundus, gastric body, gastric angle, gastric antrum and gastric pylorus could be clearly observed in both groups. The manual operating time of nine gastroenterologists was (3.67±1.95) minutes, which was shorter than that of robot operating time ((7.60±2.00) minutes), and the difference was statistically significant (t=8.445, P<0.01). The time of first in vitro operation performed by nine gastroenterologist was (13.10±6.32) minutes. The operation times of each case of nine gastrienterologist were (8.49±0.90) minutes, (7.50±1.19) minutes, (7.30±1.33) minutes and (7.12±1.61) minutes. The difference was statistically significant (F=7.901, P<0.01). Operation time gradually shortened and operation proficiency significantly improved. @*Conclusion@#Master-slave system controlled Robot-assisted flexible endoscopy 'YunSRobot’ which provides a clear observation of esophagus and stomach is safe in endoscopic examination of living animal.