Apocynin降低1型糖尿病小鼠心肌组织炎症因子的表达

Apocynin decreases cardiac cytokines in STZ-induced diabetic cardiomyopathy

目的:探讨NADPH氧化酶抑制剂apocynin对1型糖尿病小鼠心肌组织IL-1β、IL-18、TNF-α和COX-2表达的影响及其机制研究。方法:C57小鼠腹腔注射STZ建立1型糖尿病动物模型,44只8周龄雄性小鼠分为对照组(sham,n=6)、apocynin对照组(Apo,n=6)、1型糖尿病组(STZ,n=16)及1型糖尿病apocynin治疗组(STZ+Apo,n=16)。实验于8周末结束,运用超声心动图检测小鼠心脏功能,以实时定量RT-PCR技术测定心肌组织IL-1β、IL-18、TNF-α和COX-2mRNA表达,以Western blotting检测心肌组织磷酸化Akt表达。结果:1型糖尿病小鼠心脏功能降低伴随心肌组织IL-1β、IL-18、TNF-α和COX-2 mRNA表达增加,STZ+Apo组小鼠心脏功能增高伴随心肌组织IL-1β、IL-18、TNF-α和COX-2 mRNA表达减少;1型糖尿病小鼠心肌组织磷酸化Akt显著减少,STZ+Apo组心肌组织磷酸化Akt明显增加。结论:Apocynin提高1型糖尿病小鼠心脏功能伴随显著减少心肌组织IL-1β、IL-18、TNF-α和COX-2mRNA的表达,其机制可能与增加心肌组织磷酸化Akt表达密切相关。

AIM ： This study was to investigate the effects of apocynin on the expression of IL -1β, IL - 18, TNF -α and COX - 2 mRNA in the diabetic cardiomyopathy heart. METHODS ： Diabetes was induced in 8 - week old C57 mice with one intraperitoneal injection of streptozotocin （STZ, 100 mg/kg）. The experiments were divided into 4 groups ： sham （ n = 6 ） , apocynin control （ Apo, n = 6 ） , diabetic cardiomyopathy （ STZ, n = 16 ） and apocynin treatment （STZ ＋ Apo, n = 16）. At the end of 8 weeks after induction of diabetes, cardiac functions were evaluated by echocardiography. Cardiac tissue was analyzed for the expression of IL -1β, IL - 18, TNF -α, COX - 2 mRNA and phosphorylated Akt by real - time RT - PCR and Western blotting, respectively. RESULTS ： The expression of IL -1β, IL - 18, TNF -α and COX- 2 mRNA increased in diabetic cardiomyopathy heart accompanied with cardiac dysfunction. Cardiac functions were improved with decreased levels of IL -1β, IL - 18, TNF -α and COX - 2 mRNA expression in apocynin - treated heart. Compared with reduction of phosphorylated Akt, apocynin significantly increased phosphorylation of Akt in diabetic cardiomyopathy heart. CONCLUSION： Apocynin decreases cardiac IL -1β, IL - 18, TNF -α and COX -2 mRNA expression accompanied with improved cardiac function, which associates with the increase of phosphorylated Akt in diabetic cardiomyopathy heart.