摘要目的 探讨辣椒素(CAP)对2型糖尿病(T2DM)大鼠冠状动脉内皮依赖性舒张功能的影响及其机制.方法 健康清洁级6周龄雄性SD大鼠共60只,体重120~140 g,采用随机数字表法抽取45只造模为T2DM模型大鼠.采用链脲佐菌素腹腔注射并高脂饮食建T2DM大鼠动物模型;成模后将模型组分为3组:糖尿病组(15只)、CAP干预糖尿病组(CAP组,15只)及抗辣椒碱(CAPZ)干预糖尿病组(CAPZ组,15只),另设正常对照(NC)组15只,CAP组和CAPZ组分别每日腹腔注射CAP(1 mg·kg-1·d-1)和CAPZ(1.5 mg·kg-1·d-1),NC组和糖尿病组每日腹腔注射相同体积生理盐水.连续干预14周,检测各组大鼠血清空腹血糖(FPG)、总胆固醇(TC)、甘油三酯(TG)、一氧化氮(NO)、内皮型一氧化氮合酶(eNOS)及内皮素1(ET-1)水平;采用离体血管环灌流技术观察各组大鼠冠脉内皮依赖性舒张功能和非内皮依赖性舒张功能的变化;采用硝酸还原法测定冠脉NO含量;采用Western blotting法检测冠脉中瞬时受体点位香草酸亚型1通道(TRPV1)、eNOS、磷酸化eNOS(p-eNOS)的表达水平.采用配对t检验和独立样本t检验进行统计分析.结果 CAP组冠脉NO量、TRPV1和p-eNOS蛋白表达量较糖尿病组明显增加[分为(105.7±3.9)比(92.8±8.3)μmol/(mg·pro)、0.41±0.05比0.30±0.05,0.24±0.03比0.14±0.04,t=-4.47、-2.80、-3.06,P<0.05].CAP组冠脉环对不同浓度乙酰胆碱诱导的舒张率较糖尿病组明显升高(t=-20.94~10.42,均P<0.05).CAP组大鼠血清FPG、TC、TG和ET-1较糖尿病组明显降低(t=-42.29~-13.67,均P<0.05).结论 长期补充CAP可以改善糖尿病大鼠冠脉内皮依赖性舒张不全,同时改善糖尿病慢性高血糖、高血脂状态.

abstractsObjective To investigate the effects of capsaicin (CAP) on coronary endothelium-dependent vasodilation in rats with type 2 diabetes mellitus (T2DM). Methods Sixty healthy male Sprague Dawley rats (120-140 g) were used in this study. Intraperitoneal injection of streptozotocin and high fat diet were used to establish T2DM in rats. Then all diabetic rats were randomly divided into diabetes mellitus (DM) group, CAP intervention (CAP) group and capsazepine intervention (CAPZ) group with 15 rats in each group. And 15 normal rats were selected as normal control (NC) group. Rats in CAP group and CAPZ group were injected intraperitoneal with CAP (1 mg·kg-1·d-1) or CAPZ (1.5 mg·kg-1·d-1), respectively. The same volume of saline was injected to rats in NC group and DM group. After 14 weeks, the levels of fasting plasma glucose (FPG), total cholesterol (TC), triglycerides (TG), nitric oxide (NO), endothelial nitric oxide synthase (eNOS), endothelin1 (ET-1) in serum were determined. Endothelium-dependent and endothelium-independent vasodilation were examined in isolated vascular ring by perfusion technique; coronary NO concentration were checked by nitrate reduction assay; levels of coronary transient receptor potential vanilloid 1 (TRPV1), eNOS and phospho-eNOS(p-eNOS) were tested by Western blotting. Paired t test and independent sample t test were used for statistical analysis. Results The coronary NO concentration, levels of TRPV1 and p-eNOS were significantly increased in CAP group compared with those in DM group [(105.7±3.9)vs(92.8±8.3)μmol/(mg·pro),(0.41±0.05) vs (0.30±0.05), (0.24 ± 0.03) vs (0.14 ± 0.04),t=-4.47,-2.80,-3.06,all P<0.05]. The endothelium-dependent relaxation induced by different concentrations of acetylcholine were significantly higher in CAP group than in DM group (t=10.42,-5.19,-13.38,-17.46,-20.94, respectively, all P<0.05). The levels of serum FPG, TC, TG and ET-1 were significantly lower in CAP group than those in DM group (t=-13.67,-16.41,-20.39,-42.29, respectively, all P<0.05). Conclusion Long-term CAP supplementation prevents the impairment of coronary endothelium-dependent vasodilation in T2DM.