4-(4-取代苯胺基)-2-取代苯基-喹唑啉类衍生物对H_9C_2心肌细胞肥大的影响

Effects of 4-(4-substituted aniline)-2-substituted phenyl quinazoline derivatives on cardiac hypertrophy in H_9C_2 cells

目的:研究4-(4-取代苯胺基)-2-取代苯基-喹唑啉类衍生物[4-(4-substituted aniline)-2-substituted phenyl quinazoline derivatives,Q]对血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)诱导的H_9C_2心肌细胞肥大的影响。方法:体外培养H_9C_2细胞株,将培养的H_9C_2心肌细胞随机分为正常组(Con组),AngⅡ组,AngⅡ+Q高剂量(10-6 mol/L)组、AngⅡ+Q中剂量(10-7 mol/L)组、AngⅡ+Q低剂量(10-8 mol/L)组,采用激光共聚焦技术对H_9C_2细胞的形态扫描成像,利用计算机进行图像处理,对H_9C_2细胞表面积进行定性定量分析,BCA法测定蛋白浓度,MTT法测定加入不同浓度喹唑啉衍生物后心肌细胞活性,以及通过RT-PCR发测定肥大相关基因mRNA的表达。结果:与Con组相比,AngⅡ刺激H_9C_2心肌细胞后,细胞表面积明显增大(P<0.05);加入喹唑啉衍生物后,H_9C_2心肌细胞表面积明显减小(P<0.05)。AngⅡ诱导的H_9C_2心肌细胞,其总蛋白含量和肥大相关基因mRNA的表达水平都明显高于正常的H_9C_2心肌细胞(P<0.05),加入喹唑啉衍生物处理后的H_9C_2心肌细胞其肥大相关基因mRNA的表达明显下降(P<0.05)。结论:4-(4-取代苯胺基)-2-取代苯基-喹唑啉类衍生物可以改善AngⅡ诱导的H_9C_2心肌细胞肥大。

Objective：To define the effects of 4-（4-substituted aniline）-2-substituted phenyl quinazoline derivatives on cardiac hypertrophy.Method：The establishment of cardiomyopathy hypertrophy model through stimulatingH_9C_2 cells with AngⅡ.H_9C_2 cells were randomized into five groups：normal control group;AngⅡgroup;AngⅡ＋Q group（10-6 mol/L）;AngⅡ＋Q group（10-7 mol/L）;AngⅡ＋Q group（10-8 mol/L）.The surface area ofH_9C_2 was measures with a laser scanning confocal microscope technique（LSCM）.The total protein content was analyzed by BCA.The survival of cells was assayed by MTT,and the mRNA expressions of hypertrophy-related genes were detected by RT-PCR.Result：Compared with control group,the surface area ofH_9C_2 stimulated by AngⅡ was increased significantly（P〈0.05）,after joining Q,the surface area decreased observably（P〈0.05）.The level of total protein and expressions of genes of hypertrophy ofH_9C_2 stimulated by AngⅡ was increased apparently（P〈0.05）,however,those indicators were declined comparatively ofH_9C_2 handled by Q（P〈0.05）.Conclusion：Quinazoline compound can perfect AngⅡ-induced cardiomyopathy hypertrophy.