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目的:探讨羟氯喹对大鼠梗死区周边心肌共济失调毛细管扩张突变基因(ATM)下游信号分子及凋亡的影响。方法:按Maisel方法建立心肌梗死与假手术模型,将术后3 d仍存活的SD大鼠按不同干预条件分为心肌梗死羟氯喹组(A组,n=11),心肌梗死安慰剂组(B组,n=15),假手术羟氯喹组(C组,n=7),假手术安慰剂组(D组,n=7)。计算处理3个月后各组死亡率,原位TUNEL法检测心肌细胞凋亡,Western Blot测定梗死区周边心肌MMP-9、P-Akt、P53蛋白表达。结果:A、B、C、D组大鼠处理3个月后死亡率分别为9.0%、40.0%、0%、0%,心肌细胞凋亡率分别为(12±4)%、(30±5)%、(2±2)%、(3±2)%。A组与B组心肌MMP-9蛋白IA分别为0.67±0.11、1.07±0.13,P<0.05;P-Akt蛋白IA分别为1.12±0.21、0.58±0.18,P<0.05;P53蛋白IA分别为1.01±0.20、0.98±0.19,P>0.05。C组与D组心肌MMP-9蛋白IA分别为0.42±0.14、0.56±0.16,P>0.05;P-Akt蛋白IA分别为0.78±0.20、0.62±0.23,P>0.05;P53蛋白IA分别为0.49±0.22、0.32±0.19,P>0.05。结论:羟氯喹通过调控ATM的下游信号分子Akt蛋白表达及活性,可抑制梗死区周边心肌细胞凋亡,从而改善心肌梗死后心室重塑,降低死亡率。
AIM: To investigate the effects of hydroxychloroquine on signal molecules and apoptosis in downstream of myocardial dilatation gene (ATM) of ataxia in infarcted area of rats. Methods: The myocardial infarction and sham operation models were established according to the method of Maisel. The SD rats surviving 3 days after operation were divided into hydroxychloroquine group (group A, n = 11), myocardial infarction placebo group Group B, n = 15), sham surgery hydroxychloroquine (Group C, n = 7) and sham operation placebo (Group D, n = 7). The mortality of each group was calculated after 3 months of treatment. The apoptosis of cardiomyocytes was detected by TUNEL method in situ. The expression of MMP-9, P-Akt and P53 in peripheral myocardium was detected by Western Blot. Results: The mortality rates of rats in groups A, B, C and D after treatment for 3 months were 9.0%, 40.0%, 0% and 0%, respectively. The apoptosis rates of cardiomyocytes were (12 ± 4)% and 5)%, (2 ± 2)%, (3 ± 2)%. The IA of myocardial MMP-9 in group A and group B were 0.67 ± 0.11 and 1.07 ± 0.13 respectively (P <0.05); the P-Akt protein IA was 1.12 ± 0.21 and 0.58 ± 0.18, respectively, P <0.05; ± 0.20, 0.98 ± 0.19, P> 0.05. The MMP-9 protein IA in group C and group D were 0.42 ± 0.14 and 0.56 ± 0.16, respectively, P> 0.05; the P-Akt protein IA was 0.78 ± 0.20 and 0.62 ± 0.23, respectively, P> 0.05; ± 0.22, 0.32 ± 0.19, P> 0.05. CONCLUSION: Hydroxychloroquine can inhibit apoptosis of cardiac myocytes in infarct area by regulating the expression and activity of downstream signal molecule Akt in ATM, so as to improve ventricular remodeling and reduce mortality after myocardial infarction.