The loss of endothelial connective integrity and endothelial barrier dysfunction can lead to increased vascular injury, which is related to the activation of endothelial inflammasomes. There are evidences that low con...The loss of endothelial connective integrity and endothelial barrier dysfunction can lead to increased vascular injury, which is related to the activation of endothelial inflammasomes. There are evidences that low concentrations of aspirin can effectively prevent cardiovascular diseases. We hypothesized that low-dose aspirin could ameliorate endothelial injury by inhibiting the activation of NLRP3 inflammasomes and ultimately prevent cardiovascular diseases. Microvascular endothelial cells were stimulated by lipopolysaccharide(2 μg/mL) and administrated by 0.1–2 mmol/L aspirin. The wild type mice were stimulated with LPS(100 μg/kg/day), and 1 h later treated with aspirin(12.5, 62.5, or125 mg/kg/day) and dexamethasone(0.0182 mg/kg/day) for 7 days. Plasma and heart were harvested for measurement of ELISA and immunofluorescence analyses. We found that aspirin could inhibit NLRP3 inflammasome formation and activation in vitro in dose-dependent manner and has correlation between the NLRP3 inflammasome and the ROS/TXNIP pathway. We also found that low-concentration aspirin could inhibit the formation and activation of NLRP3 inflammasome and restore the expression of theendothelial tight junction protein zonula occludens-1/2(ZO1/2). We assume that aspirin can ameliorate the endothelial layer dysfunction by suppressing the activation of NLRP3 inflammasome.展开更多
目的探讨体外培养豚鼠膀胱组织ICCs细胞(interstitial cells of Cajal,ICCs)间隙连接蛋白Connexin43的表达。方法胶原酶消化法进行豚鼠膀胱组织ICCs细胞的原代培养,对照为原代培养膀胱平滑肌细胞,免疫荧光法进行两种细胞的特征性蛋白c-...目的探讨体外培养豚鼠膀胱组织ICCs细胞(interstitial cells of Cajal,ICCs)间隙连接蛋白Connexin43的表达。方法胶原酶消化法进行豚鼠膀胱组织ICCs细胞的原代培养,对照为原代培养膀胱平滑肌细胞,免疫荧光法进行两种细胞的特征性蛋白c-kit及平滑肌肌动蛋白(smooth muscle actin,SMA)染色观察,免疫荧光法及Western blot法进行培养细胞Connexin43的检测。结果豚鼠膀胱ICCs细胞特征性蛋白c-kit染色阳性,SMA染色阴性。豚鼠膀胱ICCs细胞间隙连接蛋白Connexin43表达水平较高,显著高于膀胱平滑肌细胞。结论豚鼠离体膀胱ICCs细胞间隙连接蛋白Connexin43高表达可能是其信号传递的重要物质基础。展开更多
基金supported by the National Key Research and Development Program of China(No.2017YFC1700400)National Natural Science Foundation of China(Nos.81603587 and 81603668)+4 种基金Guangdong Natural Science Funds for Distinguished Young Scholar(No.2018B030306027,China)Science and Technology Development Plan of Guangdong Province(2017A020211016,China)Science&Technology Award for Young-Aged Talents of China Association of Traditional Chinese Medicine(No.CACM-2017-QNRC2-C12)the National Institutes of Health of USA(No.HL122769)Project of Guangzhou University of Chinese Medicine(No.A1-AFD018171Z11020,China)
文摘The loss of endothelial connective integrity and endothelial barrier dysfunction can lead to increased vascular injury, which is related to the activation of endothelial inflammasomes. There are evidences that low concentrations of aspirin can effectively prevent cardiovascular diseases. We hypothesized that low-dose aspirin could ameliorate endothelial injury by inhibiting the activation of NLRP3 inflammasomes and ultimately prevent cardiovascular diseases. Microvascular endothelial cells were stimulated by lipopolysaccharide(2 μg/mL) and administrated by 0.1–2 mmol/L aspirin. The wild type mice were stimulated with LPS(100 μg/kg/day), and 1 h later treated with aspirin(12.5, 62.5, or125 mg/kg/day) and dexamethasone(0.0182 mg/kg/day) for 7 days. Plasma and heart were harvested for measurement of ELISA and immunofluorescence analyses. We found that aspirin could inhibit NLRP3 inflammasome formation and activation in vitro in dose-dependent manner and has correlation between the NLRP3 inflammasome and the ROS/TXNIP pathway. We also found that low-concentration aspirin could inhibit the formation and activation of NLRP3 inflammasome and restore the expression of theendothelial tight junction protein zonula occludens-1/2(ZO1/2). We assume that aspirin can ameliorate the endothelial layer dysfunction by suppressing the activation of NLRP3 inflammasome.
