摘要
目的探讨NADPH氧化酶选择性抑制剂Apocynin对1型糖尿病小鼠心脏功能的影响及其作用机制。方法44只8周龄雄性C57小鼠随机分为正常对照组(n=6)、Apocynm对照组(n=6)、1型糖尿病组(n=16)及1型糖尿病Apocynin治疗组(n=16)。小鼠腹腔注射链脲佐菌素(STZ)建立1型糖尿病动物模型。实验于8周末结束,记录实验小鼠生存率、测量小鼠体质量及左室质量,并计算左室质量指数。运用超声心动图技术与Langendorff灌注系统检测小鼠心脏功能;Real-time RT-PCR技术测定心肌组织α-肌球蛋白重链(α-MHC)、β-肌球蛋白重链(β-MHC)、心房钠尿肽(ANP)以及Ⅰ型(ColⅠ)和Ⅲ型(ColⅢ)胶原的表达。结果①Apocynin能提高糖尿病小鼠生存率,降低糖尿病小鼠左室质量指数(P<0.01);②Apocynin能明显改善糖尿病小鼠心脏功能,增加心脏左室射血分数、左室短轴缩短率和+dp/dt、-dp/dt(P<0.01);③Apocynin能显著降低糖尿病小鼠心肌ANP mRNA表达和β/α-MHC比值(P<0.01);④Apocynin能降低糖尿病小鼠心肌组织ColⅠ和ColⅢ胶原的表达(P<0.01)。结论Apocynin能显著改善1型糖尿病小鼠的心脏功能,其机制与降低心肌肥大特征性基因ANP表达和β/α-MHC比值以及减少心肌ColⅠ、ColⅢ胶原表达密切相关。
Objective To investigate the effects of Apocynin, the NADPH oxidase inhibitor, on cardiac function in type 1 diabetic mice and explore the mechanisms. Methods Forty-four 8-week-old C57 mice were randomly divided into control group （n = 6）, Apocynin control group（ n = 6）, type 1 diabetes group （ n = 16） and type 1 diabetes treated by Apocynin group （n = 16）. Type 1 diabetes mouse models were induced by STZ injection. Eight weeks after model establishment, the survival rate, body weight （BW）, left ventricular heart weight （LVHW） and LVHW/BW were measured, the cardiac function was analysed by ultrasound cardiography and Langendorff perfusion system, and the expression of a-myosin heavy chain （α-MHC）, B-myosin heavy chain （β-MHC）, atrial natriuretic peptide （ANP）, type Ⅰ collagen（ Col Ⅰ ）and type Ⅲ collagen（Col Ⅲ） of cardiac muscles was detected by Real-time RT-PCR. Results （1）Apocynin significantly increased the survival rate and decreased LVHW/BW in diabetic mice （ P 〈 0. 01）. （2） Apocynin significantly improved the cardiac function, increased left ventricular ejection function, left ventricular short axis fractional shortening, ＋ dp/dt and - dp/dt in diabetic mice （P 〈0.01）. （3）Apocynin significantly decreased the expression of ANP mRNA and ratios of β/α-MHC of cardiac muscles in diabetic mice （P 〈 0.01）. （4）Apocynin significantly decrease the expression of Col Ⅰ and Col Ⅲ of cardiac muscles in diabetic mice （P 〈 0.01）. Conclusion Apocynin significantly improves the cardiac function of type 1 diabetic mice, which is associated with the decreased expression of hypertrophy-related gene ANP, β/α-MHC ratio and expression of Col Ⅰ and Col Ⅲ in cardiac muscles.
出处
《上海交通大学学报（医学版）》
CAS
CSCD
北大核心
2009年第6期681-684,共4页
Journal of Shanghai Jiao tong University:Medical Science
