吉非贝齐对心肌纤维化的作用及机制研究  

Effect and mechanism of gemfibrozil on cardiac fibrosis induced by pressure overload in experimental mice

作　　者：周凯章[2] 郑理玲[3] 汪铁军[1] ZHOU Kai-Zhang;ZHENG Li-Ling;WANG Tie-Jun(Hubei Cancer Hospital,Wuhan 430079,China)

机构地区：[1]湖北省肿瘤医院,武汉430079 [2]泉州市第一医院城东分院,泉州362000 [3]福建医科大学附属泉州第一医院,泉州362000

出　　处：《中国免疫学杂志》2019年第17期2059-2063,共5页Chinese Journal of Immunology

基　　金：福建省自然科学基金项目(No.2015J01515)

摘　　要：目的:观察吉非贝齐对小鼠胸主动脉弓缩窄(TAC)术后心肌纤维化的作用并探讨可能的作用机制。方法:选取60只C57BL/6小鼠,采用TAC构建小鼠心肌重构模型,随机分为4组(每组15只):假手术+生理盐水组、假手术+吉非贝齐组、TAC+生理盐水组、TAC+吉非贝齐组,术后4周进行超声心动图检查,处死后取材,记录心重、体重、胫骨长度。应用免疫蛋白印迹(Westernblot)法检测AKT、GASK3β、ERK、P38总蛋白及相应磷酸化的表达水平。采用RT-PCR检测肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、胶原蛋白Ⅰ(CollagenⅠ)、胶原蛋白Ⅲ(CollagenⅢ)、结缔组织生长因子(CTGF)的转录水平。天狼星红染色(PSR)法测定心肌胶原沉积。免疫组化检测α-平滑肌肌动蛋白(α-SMA)的表达水平。结果:与TAC+生理盐水组相比,TAC+吉非贝齐组中左室收缩末内径、左室舒张末内径、短轴缩短率恶化程度明显改善(P<0.01),但心重比体重、心重比胫骨长未见明显改变;TNF-α、IL-1β、CollagenⅠ、CollagenⅢ以及CTGF转录水平在吉非贝齐治疗后明显降低(P<0.01);天狼星红染色以及免疫组化的结果显示,心肌胶原分数和α-SMA表达水平在吉非贝齐治疗后明显降低(P<0.01);AKT、GASK3β蛋白的磷酸化水平也在吉非贝齐干预后明显降低。而假手术+生理盐水组与假手术+吉非贝齐组相比以上指标均无明显变化。结论:吉非贝齐能够减轻压力超负荷诱导的心肌纤维化。Objective: To observe the protective roll of gemfibrozil on cardiac fibrosis induced by thoracic aorta constriction (TAC) in mice and to explore the possible mechanism. Methods: TAC was used to established myocardial remodeling model.A total of 60 C57BL/6 mice were randomly divided into 4 groups (15 per group):sham+saline group,sham+gemfibrozil group,TAC+ saline group,TAC+gemfibrozil group,echocardiography was performed 4 weeks after the operation.The heart weight,body weight and length of the tibia were recorded.Western blot was used to detect the expression of AKT,GASK3β,ERK,P38 total protein and their corresponding phosphorylation.Transcription levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),collagenⅠ(CollagenⅠ),collagenⅢ(CollagenⅢ) and connective tissue growth factor (CTGF) were detected by RT-PCR.Sirius Red Staining (PSR) method was used to measure cardiac collagen deposition.The expression of α-smooth muscle actin (α-SMA) was detected by immunohistochemistry. Results: Compared with the TAC+ saline group,the left ventricular end-systolic diameter,left ventricular end-diastolic diameter,and short-axis shortening rate were significantly improved in the TAC+gemfibrozil group ( P <0.01),but there was no significant change in the HW/BW and the HW/TL after gemfibrozil treatment.TNF-α,IL-1β,CollagenⅠ,CollagenⅢ and CTGF transcription levels were significantly decreased after gemfibrozil treatment ( P <0.01).Sirius red staining and immunohistochemistry showed that the collagen fraction and α-SMA expression level were significantly decreased after gemfibrozil treatment ( P <0.01);the phosphorylation levels of AKT and GASK3β protein were also significantly decreased after gemfibrozil administration.There was no significant change in the sham operation+saline group compared with the sham operation+gemfibrozil group. Conclusion: Gemfibrozil can relieve pressure overload induced cardiac fibrosis.

关 键 词：吉非贝齐 压力负荷 胸主动脉缩窄术 心肌纤维化 炎症 

分 类 号：R972[医药卫生—药品]