目的进一步探讨心脏衰老的机制及干预因素的影响。方法将30只20月龄的Wistar大鼠随机分为观察1组、观察2组和老年对照组各10只,设10只3月龄大鼠为青年组。观察1组、观察2组分别予阿托伐他汀1、10mg/(kg·d)灌胃,青年组和老年对照组予等体积生理盐水灌胃,均连续4个月。采用RT—PCR方法检测各组心肌过氧化物酶体增殖物激活物受体α(PPARα)mRNA和自细胞介素(IL)-1β mRNA表达水平。结果与青年对照组比较,老年对照组PPARα mRNA表达水平显著降低(P〈0.01),IL-1β mRNA表达水平显著增高(P〈0.01);与老年对照组比较,观察l组和观察2组PPARα mRNA表达水平显著升高(P〈0.01),IL-1βmRNA表达水平显著降低(P〈0.01),尤以观察2组为著。结论老年大鼠心肌IL-1βmRNA表达显著增高、PPARα mRNA表达显著降低,此可能在心脏衰老发生、发展过程中起重要作用;阿托伐他汀可通过激活PPARα抑制IL-1β异常表达,此可能为其对抗衰老、改善心脏功能的重要机制之一。
Objective To investigate the changes of the expression of PPARα mRNA and IL-1β mRNA in myocardium of aging tars and the effects of atorvastatin on it. Methods 30 Wister rats at 20 month old were divided into three groups: aging control group, observed group one[10 mg(kg·d) ], observed group two[1 mg(kg · d) ]. Another 10 Wister rats at 3 months old were selected as young control group, atorvastatin was delivered by intragastric administration to observed groups for 4 months. Normal sodium was delivered to control group by intragastric administration too. The expression of PPARα mRNA and IL-1β mRNA were evalulated by RT-PCR. Results (1)The expression level of PPARα mRNA in aging control group was significantly lower than that in the young control group(P 〈 0.01 ), atorvastatin upregulated PPARα mRNA expression in a dosage-dependent manner ( P 〈 0.05). (2)The expression level of IL-1β mRNA in aging control group was significantly higher than that in young control group(P 〈 0.01 ), atorvastatin inhibited IL-1β mRNA expression in a dosage-dependent manner ( P 〈 0.05). Conclusion Atorvastatin can inhibit the expression of IL-1β mRNA in myocardium of aging rats by upregulating the expression level of PPARα mRNA, which may be the mechanism of myocardium protection.