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目的观察维生素C(AA)和N-乙酰半胱氨酸(NAC)对糖尿病大鼠心肌缺血再灌注损伤的影响。方法 50只大鼠随机分为10组,非糖尿病对照组,非糖尿病+AA组,非糖尿病+NAC组,非糖尿病+NAME组,糖尿病对照组,糖尿病+AA组,糖尿病+NAC组,糖尿病+NAME组,糖尿病+AA+NAME组,糖尿病+NAC+NAME组,每组5只大鼠。大鼠腹腔注射链脲霉素(STZ)连续5 d,制造大鼠糖尿病模型,对照组注射PBS。28 d后大鼠处死取出心脏,制作离体缺血再灌注模型,在缺血再灌注前按分组分别给以AA、NAC和L-NAME,心脏缺血30 min后再灌住120 min。实验后去大鼠心脏组织测量心肌谷胱甘肽(GSH/GSSG)、生物蝶呤(BH4/BH2)、超氧化物、硝基酪氨酸(NT)、氮氧化物(NOx)和心肌梗死面积的变化。组间比较用单因素方差分析。结果 AA和NAC显著提高了糖尿病大鼠心脏的BH4/BH2比率,降低了超氧化合物含量和硝基酪氨酸(NT)含量,提升了氮氧化物(NOx)产量。在缺血再灌注前预先给以AA和NAC可以提高糖尿病大鼠的左心室(LV)功能并且减小梗死面积。在非糖尿病大鼠中则没有效果。一氧化氮合成酶抑制剂(L-NAME)抑制超氧化物、NT和NOx的产生,使糖尿病大鼠LV功能恶化并且增加梗死面积。L-NAME也可以抵消由AA和NAC增加NOx对提高LV功能和限制梗死面积的效果。结论使用AA和NAC提高了糖尿病大鼠心脏的BH4/BH2比率并且防止NOS解偶联,增加了一氧化氮的生物利用率,可以对糖尿病大鼠心脏的缺血再灌注损伤进行有效保护。
Objective To observe the effects of vitamin C (AA) and N-acetylcysteine (NAC) on myocardial ischemia-reperfusion injury in diabetic rats. Methods Fifty rats were randomly divided into 10 groups: non-diabetic control group, non-diabetic + AA group, non-diabetic + NAC group, non-diabetic + NAME group, diabetic control group, diabetic + AA group, diabetic + NAC group, NAME group, diabetes + AA + NAME group, diabetes + NAC + NAME group, 5 rats in each group. The rats were injected intraperitoneally with streptozotocin (STZ) for 5 days to make diabetic rat model, while the control group were injected with PBS. After 28 days, the rats were sacrificed and the heart was removed. The model of ischemia-reperfusion was established. AA, NAC and L-NAME were given before ischemia-reperfusion. The hearts were reperfused for 120 min after 30 min of ischemia. Myocardial glutathione (GSH / GSSG), biotin (BH4 / BH2), superoxide, nitrotyrosine (NT), nitric oxide (NOX) and myocardial infarction Area changes. One-way analysis of variance was used to compare between groups. Results AA and NAC significantly increased the BH4 / BH2 ratio in the heart of diabetic rats, decreased the content of superoxide and nitrotyrosine (NT), and promoted the production of nitrogen oxides (NOx). Pre-administration of AA and NAC before ischemia-reperfusion can increase left ventricular (LV) function and reduce infarct size in diabetic rats. There is no effect in non-diabetic rats. Nitric oxide synthase inhibitor (L-NAME) inhibits the production of superoxide, NT and NOx, worsens LV function and increases infarct size in diabetic rats. L-NAME also counteracts the effect of increased NOx by AA and NAC on increasing LV function and limiting infarct size. Conclusions AA and NAC can increase the BH4 / BH2 ratio and prevent the uncoupling of NOS in diabetic rat heart, increase the bioavailability of nitric oxide and protect the heart from ischemia-reperfusion injury in diabetic rats.