Objective To investigate the expression of inositol requiting enzyme1 α (IRE1 α) and tumor necrosis factor receptor-associated factor 2 (TRAF2) and its significance through establishing models of intestinal ischemia reperfusion injury (IIRI) in rats.Methods According to the random number table,50 male SD rats were randomly divided into 2 groups:sham operation group (n =10) and ischemia reperfusion (I/R) group (n =40).Sham group animals underwent laparotomy.I/R group rats were subjected to occlusion of the superior mesenteric artery for 30 min;then the blood flow was restored.I/R group animals were divided into 4 subgroups:2 h,6 h,12 h,24 h according to the time of reperfusion.Eight rats were examined based on the number of live rats in each subgroup.The HE staining pathological changes in intestinal samples were observed by the light microscope.The small intestinal epithelial cell apoptosis index (AI) was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL).The expression levels of intestinal tissues tumor necrosis factor α (TNF-α) and plasma intestinal fatty acid-binding protein (Ⅰ-FABP) were detected by ELISA tests.Situ end labeling method was used to detect intestinal cell AI.Western blot was applied to investigate the expression of endoplasmic reticulum stress(ERS) proteins IRE1α,phosphorylation IREIα (p-IRE1 α) and TRAF2 in all group rats intestinal tissues.Results (1)The pathological changes showed that the intestinal injury of I/R groups was more severe than that of sham group,especially at 6 h.(2) Compared with sham group,the expression levels of TNF-α [sham group (16.41 ± 4.44)ng/ L,2 h group:(79.71 ± 8.20) ng/L,6 h group:(131.70 ± 11.59) ng/L,12 h group:(94.23 ±7.66) ng/L,24 h group:(69.78 ± 9.58) ng/L],AI[sham group:(3.93 ±0.77)％,2 h group:(16.24 ± 1.97)％,6 h group:(42.19 ±2.40)％,12 h group:(37.79 ± 2.34)％,24 h goup:(10.38 ±1.46)％] and plasma Ⅰ-FABP [sham group:(0.65 ±0.10) × 103 ng/L,2 h group:(1.47 ±0.10) ×103 ng/L,6 h group:(2.36 ±0.17) ×103 ng/L,12 h group:(37.79 ±2.34) ×103 ng/L,24 group:(l.41 ±0.09) × 103 ng/L] were higher (F =231.462,149.032,162.491,all P ＜ 0.01).(3) The expression of TRAF-2 protein and p-IRE1 α/IRE1 α could be up-regulated after IIRI (F =40.473,59.59,P ＜ 0.01).The expression of these proteins was up-regulated 2 h after reperfusion,peaking at 6-12 h reperfusion,and then decreased at 24 h,and the variation tendencies of all groups were the same.Conclusions IIRI could induce ERS,activate IRE1 α and up-regulate TRAF2.IRE1α/TRAF2 mediating ERS might be involved in regulating the cell inflammation,apoptosis and increasing intestinal permeability after IIRI.

Objective:To investigate the effects of tamoxifen on high glucose-induced epithelial-to-mesenchymal transition of rat peritoneal mesothelial cells and the underlying mechanism.Methods:The peritoneal mesothelial cells of normal male SD rats were selected between January 2015 and June 2016 and then cultured and divided into blank control, high-glucose stimulation and drug intervention groups. High-glucose stimulation group: primary cultured rat peritoneal mesothelial cells (RPMCs) were treated with 60 mmol/L high-concentration glucose to induce epithelial-to-mesenchymal transition. Drug intervention group: (1) RPMCs were treated with 60 mmol/L high-concentration glucose and different concentrations (0.5 μmol/L, 2 μmol/L) of tamoxifen. After 72 hours of stimulation, protein was extracted. (2) RPMCs were treated with 60 mmol/L high-concentration glucose and 2 μmol/L tamoxifen with or without 2 μmol/L ER-α antagonist for 1 hour to extract protein and for 6 hours to extract RNA. (3) RPMCs were treated with high-concentration glucose and 2 μmol/L tamoxifen with or without 1 μmol/L 1 μM proteasome inhibitor for 1 hour to extract protein. Western blot analysis was performed to analyze change in E-cadherin, α-SMA, Smad2, p-Smad2, Smad3, p-Smad3 and Smad4 protein. Real-time fluorescence quantitative PCR was performed to detect the change in mRNA expression of Smad2, Smad3, connective tissue growth factor and plasminogen activator inhibitor 1.Results:Tamoxifen attenuated epithelial-to-mesenchymal transition on RPMCs induced by high-level glucose, showing increased expression of epithelial cell marker E-cadherin and decreased expression of α-SMA in a concentration-dependent manner ( tE-cadherin = 2.31, tα-SMA =-2.53, both P < 0.05).TGF-β1/R-Smad signal pathway was activated by high-concentration glucose. Phosphorylation of Smad2/3 and mRNA expression of CTGF and PAI-1 were increased. Tamoxifen remarkably reduced protein and mRNA level of above mentioned protein and related target genes ( tp-Smad2 = -3.38, tCTGF = -3.81, P < 0.05), which could be blocked by ER-α antagonist. Finally, proteasome inhibitor could weaken the inhibitory effects of tamoxifen on p-Smad2/3 and increase p-Smad2/3 protein level ( tp-Smad2 = 3.94, P < 0.05). Conclusion:Tamoxifen activates ER-α on RPMCs, weakens the activation of TGF-β1/R-Smad signal pathway through decreasing p-Smad2 protein level, and effectively inhibits the progression of high-concentration glucose-induced epithelial-to-mesenchymal transition possibly through degrading p-Smad2 protein through proteasome. The role of tamoxifen in epithelial-to-mesenchymal transition may provide a possible guide for research, prevention and treatment of peritoneal fibrosis.

Objective:To investigate the relationship between central venous-arterial blood carbon dioxide partial pressure difference (Pcv-aCO 2) and left ventricular ejection fraction(LVEF) in acute myocardial infarction. Methods:Clinical data of patients with acute myocardial infarction admitted to the Intensive Care Unit of Fujian Provincial Hospital from November 2019 to October 2021 were retrospectively analyzed. LVEF was measured by bedside echocardiogram. The patients were divided into the normal LVEF group (LVEF ≥ 52%) and decreased LVEF group (LVEF < 52%) according to LVEF. The differences in general information and hemodynamic parameters between the two groups were compared. The normality of the above data was tested by the Jarque-Bera test. Correlation analysis of hemodynamic indices with LVEF was performed. Binary logistic regression was used to analyze the risk factors associated with the decrease in LVEF. The feasibility of diagnosing LVEF decline with Pcv-aCO 2 was assessed using receiver operating characteristic (ROC) curve. Results:Seventy-two patients with acute myocardial infarction were included for analysis, including 25 patients in the normal LVEF group and 47 patients in the decreased LVEF group. Pcv-aCO 2 was significantly higher in the decreased LVEF group than that in the normal LVEF group [(7.13±1.19) mmHg vs. (5.41±1.23) mmHg, P<0.01]. There was a negative correlation between LVEF and Pcv-aCO 2 ( rs= -0.740, P<0.01). The area under the ROC curve for Pcv-aCO 2 was 0.849 (95% CI: 0.758-0.939, P<0.01). The binary logistic regression analysis showed that Pcv-aCO 2 was an independent risk factor for decreased LVEF ( OR=2.251, 95% CI: 1.326-3.820). Conclusions:To a certain extent, the increase of Pcv-aCO 2 can predict the decrease of LVEF in acute myocardial infarction.