二肽基肽酶4抑制剂抑制Wnt/β-catenin信号通路改善慢性心力衰竭大鼠心肌纤维化  

Dipeptidyl peptidase 4 inhibitor improved myocardial fibrosis in rats with chronic heart failure via inhibiting Wnt/β-catenin signaling pathway

作　　者：张迪[1] 石菲菲[1] 辛雨[1] 马淑梅[1] ZHANG Di;SHI Fei-fei;XIN Yu;MA Shu-mei(Department of Cardiology, Shengjing Hospital Affiliated to China Medical University, Shenyang 110004, China)

机构地区：[1]中国医科大学附属盛京医院心内科

出　　处：《解剖科学进展》2019年第4期390-394,共5页Progress of Anatomical Sciences

基　　金：辽宁省自然科学基金(20180551091)

摘　　要：目的探讨二肽基肽酶4(DPP-4)抑制剂对慢性心力衰竭大鼠心肌纤维化的影响及与Wnt/β-catenin信号通路的关系。方法将50只SPF级SD大鼠,体重(200±20)g,随机分为对照组(Control group)、模型组(Model group)、二肽基肽酶4抑制剂组(DPP-4inhibitor group)、氯化锂组(LiClgroup)及氯化锂+DPP-4组(LiCl+DPP-4inhibitor group),每组10只。利用腹腔注射阿霉素(2.5mg/kg)的方法构建慢性心力衰竭大鼠模型。利用超声检测各组大鼠心功能;HE及Masson染色检测各组大鼠心脏病理学改变;Western blot检测各组大鼠心脏组织中TGF-β1,α-SMA,GSK-3β,p-GSK-3β及β-catenin蛋白的表达。结果与模型组相比,DPP-4inhibitor组大鼠心功能显著改善,心脏组织病理损伤及心肌纤维化减轻,心脏组织中TGF-β1和α-SMA蛋白表达明显减少,p-GSK-3β及β-catenin蛋白表达也显著降低(P<0.05);LiCl加重慢性心力衰竭大鼠模型的心脏功能、病理损伤及心肌纤维化程度,增加TGF-β1和α-SMA蛋白表达,并显著增加p-GSK-3β及β-catenin蛋白表达;但是DPP-4抑制剂能够减轻甚至部分逆转LiCl对慢性心力衰竭大鼠的影响。结论二肽基肽酶4抑制剂改善慢性心力衰竭大鼠心肌纤维化,与抑制Wnt/β-catenin信号通路相关蛋白表达相关。Objective To investigate the effect and possible mechanism of dipeptidyl peptidase 4(DPP-4) inhibitor on myocardial fibrosis in chronic heart failure rats. Methods 50 SPF SD rats weighing( 200± 20) g were randomly averagely divided into control group, model group, DPP-4 inhibitor group, and lithium chloride Group(LiCl group) and lithium chloride+DPP-4 group(LiCl + DPP-4 inhibitor group). A rat model of chronic heart failure was constructed by intraperitoneal injection of doxorubicin(2.5 mg/kg). The cardiac function was detected by ultrasound. The pathological changes of heart were detected by HE and Masson staining. The expressions of TGF-β1,α-SMA, GSK-3β, p-GSK-3β and β-catenin proteins in the heart tissue were detected by Western blot. Results DPP-4 inhibitor significantly improved cardiac function, alleviated cardiac histopathological damage and myocardial fibrosis, compared with the model group. The expression levels of TGF-β1,α-SMA, p-GSK-3β and β-catenin proteins in cardiac tissue was significantly decreased in DPP-4 inhibitor group than in model group(P<0.05). Li Cl aggravated cardiac function, pathological damage and myocardial fibrosis, increased the expression levels of TGF-β1,α-SMA, p-GSK-3β and β-catenin proteins in a rat model of chronic heart failure. However, DPP-4 inhibitor alleviated or even partially reversed the effect of LiCl on chronic heart failure rats. Conclusion Dipeptidyl peptidase 4 inhibitor improved myocardial fibrosis in rats with chronic heart failure, which is related to the inhibition of Wnt/β-catenin signaling pathway-related proteins expression.

关 键 词：慢性心力衰竭 二肽基肽酶4抑制剂 阿霉素 WNT/Β-CATENIN信号通路 

分 类 号：R541.6[医药卫生—心血管疾病]