摘要
目的初步探究盘状结构域受体1(DDR1)对高糖诱导血管内皮凋亡的影响。方法腹腔注射链脲佐菌素(STZ)构建糖尿病大鼠模型(12周),血管多普勒超声检测主动脉内皮功能;HE染色观察主动脉内皮结构;Western blot检测凋亡相关蛋白(caspase-3、Bax、Bcl-2)表达;免疫组织化学和Western blot检测DDR1表达与分布。高糖(33 mmol·L-1)处理HUVECs 48 h,Hoechst染色检测细胞凋亡;转染DDR1 siRNA后检测细胞凋亡情况与凋亡相关蛋白表达。结果糖尿病大鼠主动脉内皮出现严重损伤。Bax、caspase-3和DDR1表达显著升高,Bcl-2表达显著降低(P<0.05,P<0.01)。高糖处理HUVECs亦可上调Bax、caspase-3和DDR1,下调Bcl-2表达(P<0.05,P<0.01),诱导细胞凋亡。siRNA DDR1可降低高糖诱导的凋亡阳性细胞率增加(P<0.05,P<0.01),下调Bax和caspase-3,上调Bcl-2表达(P<0.05)。结论高糖可通过促进DDR1蛋白表达,诱导血管内皮细胞凋亡,导致血管内皮损伤。
Aim To investigate the effect of DDR1 in high glucose-induced vascular endothelial apoptosis.Methods Diabetic rat model was established by intraperitoneal injection of streptozotocin(STZ)for 12 weeks.Rat aortic endothelial function was detected by vascular Doppler ultrasonography;aortic endothelial structure was observed by HE staining;the expression of apoptosis-related proteins(caspase-3,Bax,Bcl-2)were detected by Western blot;The expression and distribution of DDR1 in vascular tissues were detected by immunohistochemistry and Western blot.HUVECs were treated with high glucose(33 mmol·L-1)for 48 h,and the apoptosis was detected by Hoechst staining;cell apoptosis and the expression of apoptosis-related proteins(caspase-3,Bax,Bcl-2)after transfection of DDR1 siRNA were assessed as well.Results The aortic endothelium was seriously damaged in diabetic rats.The expression of Bax,caspase-3 and DDR1 significantly increased,whereas the expression of Bcl-2 significantly decreased in aortic tissues(P<0.05,P<0.01).High glucose up-regulated Bax,caspase-3 and DDR1 protein experssion,down-regulated Bcl-2 protein expression and induced apoptosis in HUVECs(P<0.05,P<0.01).siRNA DDR1 reduced the rate of apoptosis-positive cells(P<0.05,P<0.01),down-regulated Bax and caspase-3,and up-regulated Bcl-2 expression in high glucose(P<0.05).Conclusions High glucose could induce vascular endothelial cell apoptosis by promoting DDR1 protein expression,leading to vascular endothelial damage.
作者
赵为陈
沈炳香
何春远
王法财
江俊麟
ZHAO Wei-chen;SHEN Bing-xiang;HE Chun-yuan;WANG Fa-cai;JIANG Jun-lin(Dept of Pharmacy,Lu′an Hospital,Anhui Medical University,Lu′an Anhui 237005,China;Dept of Pharmacology,Xiangya School of Pharmaceutical Sciences,Central South University,Changsha 410078,China)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2020年第6期821-827,共7页
Chinese Pharmacological Bulletin
基金
湖南省自然科学基金资助项目(No 2018JJ2543)。
关键词
糖尿病
血管病变
高糖
盘状结构域受体1
内皮细胞
凋亡
diabetes mellitus
vascular disease
high glucose
discoid domain receptor 1
endothelial cells
apoptosis