ω⁃3多不饱和脂肪酸对心肌肥厚大鼠心肌细胞外基质重塑的影响
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四川省教育厅科研课题(14ZA0137)


Effects of omega⁃3 polyunsaturated fatty acids on myocardial extracellular matrix remodeling in rats with cardiac hypertrophy
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    摘要:

    目的:探讨ω-3多不饱和脂肪酸(ω-3 polyunsaturated fatty acids,n-3PUFAs)对腹主动脉缩窄(abdominal aorta coarctation,AAC)术后心肌肥厚大鼠心肌细胞外基质重塑的影响。方法:雄性SD大鼠40只,随机分为假手术组、模型组。模型组大鼠行AAC术。术后1周,再随机将模型组分成AAC组、AAC+ n-3PUFAs低剂量组、AAC+ n-3PUFAs高剂量组,每组8只,后两组分别予以400 mg/(kg·d)及1 000 mg/(kg·d)的n-3PUFAs灌胃,假手术组和AAC组给予等体积生理盐水灌胃。8周后处死大鼠,留取心肌组织测定左心室质量指数(LVW/BW)和心脏质量指数(HW/BW),取心肌组织行HE染色及Masson染色,取血清用碱水解法测定羟脯氨酸含量,用免疫蛋白印迹(Western blot)法分析心肌组织基质金属蛋白酶9(matrix metalloproteinase 9,MMP-9)、基质金属蛋白酶抑制剂-1(tissue inhibitor of metalloproteinase-1,TIMP-1)及纤连蛋白(fibronectin,FN)的表达。结果:与假手术组相比,模型组LVW/BW、HW/BW、羟脯氨酸含量明显升高(P < 0.05),病理染色示心肌细胞肥大,胶原纤维增加,MMP-9表达增加,TIMP-1含量减少,FN表达增加,差异有统计学意义(P < 0.05)。与AAC组相比,AAC+ n-3PUFAs低剂量组、AAC+ n-3PUFAs高剂量组LVW/BW、HW/BW、羟脯氨酸含量降低,病理染色示心肌细胞肥大减轻、胶原含量减少,MMP-9、FN表达减少,TIMP-1表达增加(P < 0.05)。且AAC+ n-3PUFAs高剂量组较AAC+ n-3PUFAs低剂量组各项指标变化更为明显,差异均有统计学意义(P < 0.05)。结论:n-3PUFAs对心肌肥厚有保护作用,其机制可能与抑制MMP-9、FN的过度表达,上调TIMP-1的表达,影响心肌细胞外基质重塑相关。

    Abstract:

    Objective:To investigate the effects of omega-3 polyunsaturated fatty acids(n-3 PUFAs)on myocardial extracellular matrix remodeling in rats with myocardial hypertrophy after abdominal aortic coarctation(AAC). Methods:Forty male Sprague-Dawley rats were randomly divided into sham operation group(group A)and model group. AAC was performed in model group. One week after operation,the model group was randomly divided into three groups:AAC group(group B),AAC + n-3PUFAs low dose group(group C),AAC+ n-3PUFAs high dose group(group D). The group C and group D were given by gavage 400 mg/(kg·d)and 1 000 mg/(kg·d)n-3 PUFAs respectively,and the group A and group B were given an equal volume of normal saline. After 8 weeks,the rats were sacrificed,and the left ventricular mass index(LVW/BW)and cardiac mass index(HW/BW)were measured. The myocardial tissues were stained with HE and Masson. The serum hydroxyproline was determined by alkaline hydrolysis method. The content of matrix metalloproteinase-9(MMP-9),tissue inhibitor of metalloproteinase-1(TIMP-1)and fibronectin(FN)in myocardial tissue were analyzed by Western blot. Results:Compared with the group A,LVW/BW,HW/BW,and hydroxyproline content in groups B,C,and D increased significantly(P < 0.05). Pathological staining showed cardiomyocyte hypertrophy,collagen fiber and MMP-9 expression increasing. The expression of TIMP-1 decreased(P < 0.05). The expressions of FN in groups B,C and D were significantly higher than that in group A(P < 0.05). Compared with group B,LVW/BW,HW/BW,and hydroxyproline content in group C and group D decreased,the myocardial cells shown less hypertrophy by pathological staining and the collagen content also decreased,and MMP-9 and FN expression decreased,whereas TIMP-1 expression increased(P < 0.05). Compared with group C,the changes of all the above indexes in group D were greater(P < 0.05). All these differences have statistical significance. Conclusion:n-3PUFAs have protective effects on myocardial hypertrophy after abdominal aortic coarctation. The mechanism may be related to the inhibition of overexpression of MMP-9 and FN,the up-regulation of TIMP-1 expression,and the influence on the changes in extracellular matrix components.

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蒋松辰,高尚远,谢发江,赵 佳,江 凤.ω⁃3多不饱和脂肪酸对心肌肥厚大鼠心肌细胞外基质重塑的影响[J].南京医科大学学报(自然科学版),2019,(7):960-965

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  • 收稿日期:2018-11-21
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  • 在线发布日期: 2019-08-01
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