黄素腺嘌呤二核苷酸通过激活SCAD抑制大鼠病理性心肌肥厚和心肌纤维化  

FAD inhibits pathologi calcardiac hypertrophy and cardiac fibrosis in SHR through activating SCAD

作　　者：马智超 秦学 廖英勤 钟小艺 苏永少 刘培庆 路静 周四桂[1] MA Zhichao;QIN Xue;LIAO Yingqin;ZHONG Xiaoyi;SU Yongshao;LIU Peiqing;LU Jing;ZHOU Sigui(Department of Clinical Pharmacy,Guangdong Pharmaceutical University,Guangzhou,Guangdong 510006,China;Department of Pharmacology and Toxicology,School of Pharmaceutical Sciences,Sun Yat-sen University,Guangzhou,Guangdong 510006,China)

机构地区：[1]广东药科大学临床药学系,广东省广州市510006 [2]中山大学药学院药理与毒理学实验室,广东省广州市510006

出　　处：《中国动脉硬化杂志》2020年第5期421-428,共8页Chinese Journal of Arteriosclerosis

基　　金：国家自然科学基金项目(81670239);广东省自然科学基金项目(2016A030313729);广东药科大学“创新强校工程”资助项目(2017SFKC27)。

摘　　要：目的探究黄素腺嘌呤二核苷酸(FAD)在自发性高血压大鼠病理性心肌肥厚和心肌纤维化中的作用及防治机制。方法选取12周龄的自发性高血压大鼠(SHR)及周龄匹配的Wistar大鼠。经尾静脉注射FAD(每天1μmol/kg)治疗10周后,采用无创血压测量仪检测大鼠的血压及心率;超声心动图和组织学方法观察病理性心肌肥厚和心肌纤维化程度;Western blot方法检测短链酰基辅酶A脱氢酶(SCAD)、CollagenⅠ、CollagenⅢ、α-SMA的蛋白表达水平;免疫荧光单标法进一步验证SCAD的蛋白表达水平;荧光定量PCR检测SCAD、ANF、脑利钠肽(BNP)以及CollagenⅠ、CollagenⅢ、α-SMA的mRNA表达水平;检测SCAD酶活性、ATP、游离脂肪酸、BNP及活性氧含量。结果自发性高血压大鼠经FAD治疗后,收缩压和心率均明显降低;病理性心肌肥厚和心肌纤维化程度得到明显改善;心肌组织中SCAD的mRNA、蛋白表达、酶活性及ATP含量均显著增高,游离脂肪酸和活性氧水平明显降低(P<0.05)。结论FAD可能通过激活SCAD,改善心肌能量代谢,减少氧化应激,从而抑制自发性高血压大鼠病理性心肌肥厚和心肌纤维化。Aim To observe the effects of flavin adenine dinucleotide(FAD)on cardiac hypertrophy and cardiac fibrosis in spontaneously hypertensive rats(SHR),and to explore the mechanism of FAD on preventing and treating cardiac hypertrophy and cardiac fibrosis.Methods 12-week-old SHR and age-matched Wistar rats were selected and divided into Wistar control group,Wistar experimental group,SHR control group and SHR experimental group.After treated with FAD(1μmol/(kg·d))in the tail vein for 10 weeks,the sysbolic blood pressure and heart rate of the rats were detected by non-invasive blood pressure measuring instrument.Cardiac hypertrophy and cardiac fibrosis were observed by echocardiography and histology.The protein expression levels of SCAD(short-chain acyl-CoA dehydrogenase),CollagenⅠ,CollagenⅢandα-SMA were detected by Western blot.Immunofluorescence single-label method was used to further verify the protein expression level of SCAD.The mRNA expression levels of SCAD,ANF,BNP,CollagenⅠ,CollagenⅢandα-SMA were detected by quantitative PCR.SCAD enzyme activity,content of ATP,free fatty acids,brain natriuretic peptide(BNP)and reactive oxygen were detected.Results Systolic blood pressure and heart rate in SHR were significantly decreased after FAD treatment.Cardiac hypertrophy and cardiac fibrosis were significantly improved.SCAD mRNA,protein expression,enzyme activity and ATP content in the cardiac muscle of SHR were significantly increased.The levels of free fatty acids and reactive oxygen were significantly reduced(P<0.05).Conclusion FAD may inhibit cardiac hypertrophy and cardiac fibrosis in SHR through activating SCAD,improving cardiac energy metabolism and reducing oxidative stress.

关 键 词：黄素腺嘌呤二核苷酸 短链酰基辅酶A脱氢酶 病理性心肌肥厚 心肌纤维化 心肌能量代谢 

分 类 号：R5[医药卫生—内科学]