PDTC通过抑制NF-κB及Wnt/β-catenin信号通路修复1型糖尿病大鼠主动脉病变  

PDTC repairs aortic lesions in type 1 diabetic rats by inhibiting NF-κB and Wnt/β-catenin signaling pathways

作　　者：刘晶晶[1,2,3,4] 林桂明[1,2,3,4] 王丽颖 王燕[2,3,4] 李军 牟艳玲 LIU Jing-jing;LIN Gui-ming;WANG Li-ying;WANG Yan;LI Jun;MOU Yan-ling(School of Medicine and Life Sciences,University of Jinan-Shandong Academy of Medical Sciences,Jinan 250200,China;Institute of Materia Medica,Shandong Academy of Medical Sciences,Jinan 250062,China;Key Lab for Biotech-Drugs Ministry of Health,Jinan 250062,China;Key Lab for Rare&Uncommon Diseases of Shandong Province,Jinan 250062,China;Shandong Electric Power Center Hospital,Internal Medicine-Cardiovascular Dept,Jinan 250001,China)

机构地区：[1]济南大学山东省医学科学院医学与生命科学学院,山东济南250200 [2]山东省医学科学院药物研究所,山东济南250062 [3]国家卫生部生物技术药物重点实验室,山东济南250062 [4]山东省罕少见病重点实验室,山东济南250062 [5]山东省电力中心医院心内科,山东济南250001

出　　处：《中国药理学通报》2018年第11期1622-1627,共6页Chinese Pharmacological Bulletin

基　　金：山东省自主创新及成果转化专项(No 2014ZZCX02105);山东省医学科学院医药卫生科技创新工程

摘　　要：目的检测NF-κB活化抑制剂PDTC对NF-κB及Wnt/β-catenin信号通路的影响,明确其在糖尿病大鼠主动脉病变发生、发展中的作用。方法♂SD大鼠腹腔注射链脲佐菌素建立1型糖尿病大鼠模型,取模型成功大鼠,分为糖尿病4周、8周模型组,以及PDTC 4周、8周给药组。观察主动脉病理结构变化;检测主动脉相关蛋白、基因的表达变化。结果与正常组比较,1型糖尿病大鼠血糖值明显升高(P<0.01),8周PDTC组大鼠血糖比糖尿病组明显下降(P<0.01);显微镜下可见糖尿病大鼠主动脉血管壁增厚、平滑肌细胞增生等,PDTC组大鼠主动脉病变有所缓解。与糖尿病组比较,PDTC组IκBα、β-catenin、NF-κB p65蛋白表达明显降低(P<0.01)。结论 PDTC可能通过抑制NF-κB及Wnt/β-catenin信号通路在糖尿病大鼠体内的激活,参与修复糖尿病大鼠的主动脉损伤。Aim To observe the effect of PDTC on the alteration of NF-κB and Wnt/β-catenin signaling pathways in type 1 diabetic rats’aorta,and to clarify its role in the development of diabetes aortic diseases.Methods The type 1 diabetes rat model was established by injection of streptozocin after one-week adaptive feeding.The successful modeling rats were randomly divided into diabetes mellitus(DM)model group of four weeks and eight weeks,PDTC group of four weeks and eight weeks.HE staining was used to observe the pathological changes of aortal structures.The alteration of related proteins in aorta were determined by Western blot and qRT-PCR.Results Compared with control group,FBG levels of type 1 diabetic rats significantly increased(P<0.01),while compared with DM group,FBG levels of eight weeks PDTC group significantly decreased(P<0.01).Aortic histological analysis revealed that DM induced the increase of the thickness of vessel wall and the elastic membrane area,DM also induced the proliferation of vascular smooth muscle cells,and compared with DM group,these symptoms were eased in PDTC group of eight weeks.Compared with DM group,the expression of IκBα,β-catenin,p-NF-κB p65 levels in PDTC group of eight weeks decreased significantly(P<0.01).Conclusion PDTC could inhibit the activation of NF-κB and Wnt/β-catenin signaling pathways in diabetic rats,and participate in the repair of aortal injury in diabetic rats.

关 键 词：1型糖尿病 主动脉损伤 NF-ΚB Wnt/β-catenin PDTC GSK-3Β 

分 类 号：R322.121[医药卫生—人体解剖和组织胚胎学] R329.25[医药卫生—基础医学]