Department of Internal Medicine, Botucatu Medical School, Sao Paulo State University, UNESP, Botucatu, SP, Brazil.
Sagrado Coração University, Bauru, SP, Brazil.
Cardiovasc Diabetol. 2018 Jan 17;17(1):15. doi: 10.1186/s12933-017-0657-9.
Increased reactive oxygen species (ROS) generation in diabetes mellitus (DM) is an important mechanism leading to diabetic cardiomyopathy. Apocynin, a drug isolated from the herb Picrorhiza kurroa, is considered an antioxidant agent by inhibiting NADPH oxidase activity and improving ROS scavenging. This study analyzed the influence of apocynin on cardiac remodeling in diabetic rats.
Six-month-old male Wistar rats were assigned into 4 groups: control (CTL, n = 15), control + apocynin (CTL + APO, n = 20), diabetes (DM, n = 20), and diabetes + apocynin (DM + APO, n = 20). DM was induced by streptozotocin. Seven days later, apocynin (16 mg/kg/day) or vehicle was initiated and maintained for 8 weeks. Left ventricular (LV) histological sections were used to analyze interstitial collagen fraction. NADPH oxidase activity was evaluated in LV samples. Comparisons between groups were performed by ANOVA for a 2 × 2 factorial design followed by the Bonferroni post hoc test.
Body weight (BW) was lower and glycemia higher in diabetic animals. Echocardiogram showed increased left atrial diameter, LV diastolic diameter, and LV mass indexed by BW in both diabetic groups; apocynin did not affect these indices. LV systolic function was impaired in DM groups and unchanged by apocynin. Isovolumic relaxation time was increased in DM groups; transmitral E/A ratio was higher in DM + APO compared to DM. Myocardial functional evaluation through papillary muscle preparations showed impaired contractile and relaxation function in both DM groups at baseline conditions. After positive inotropic stimulation, developed tension (DT) was lower in DM than CTL. In DM + APO, DT had values between those in DM and CTL + APO and did not significantly differ from either group. Myocardial interstitial collagen fraction was higher in DM than CTL and did not differ between DM + APO and CTL + APO. Serum activity of antioxidant enzymes glutathione peroxidase, superoxide dismutase (SOD), and catalase was lower in DM than CTL; apocynin restored catalase and SOD levels in DM + APO. Myocardial NADPH oxidase activity did not differ between groups.
Apocynin restores serum antioxidant enzyme activity despite unchanged myocardial NADPH oxidase activity in diabetic rats.
糖尿病（DM）中活性氧（ROS）的产生增加是导致糖尿病心肌病的重要机制。白藜芦醇是从苦玄参中分离出来的一种药物，被认为是一种抗氧化剂，通过抑制 NADPH 氧化酶活性和改善 ROS 清除来发挥作用。本研究分析了白藜芦醇对糖尿病大鼠心脏重构的影响。
将 6 个月大的雄性 Wistar 大鼠分为 4 组：对照组（CTL，n=15）、对照组+白藜芦醇（CTL+APO，n=20）、糖尿病组（DM，n=20）和糖尿病+白藜芦醇组（DM+APO，n=20）。DM 由链脲佐菌素诱导。7 天后，开始给予白藜芦醇（16mg/kg/天）或载体，并持续 8 周。使用左心室（LV）组织学切片分析间质胶原分数。评估 LV 样本中的 NADPH 氧化酶活性。采用 2×2 析因设计的方差分析比较组间差异，然后进行 Bonferroni 事后检验。
糖尿病动物的体重（BW）较低，血糖水平较高。超声心动图显示，两组糖尿病动物的左心房直径、LV 舒张直径和 LV 质量均增加，而白藜芦醇对这些指数无影响。LV 收缩功能在 DM 组受损，而白藜芦醇未改变。DM 组等容舒张时间延长，DM+APO 组的二尖瓣口血流 E/A 比值高于 DM 组。通过乳头肌制备进行心肌功能评估显示，两组 DM 动物在基础条件下的收缩和舒张功能均受损。在正性肌力刺激后，DM 组的发展张力（DT）低于 CTL 组。DM+APO 组的 DT 值介于 DM 组和 CTL+APO 组之间，与两组均无显著差异。DM 组的心肌间质胶原分数高于 CTL 组，而 DM+APO 组与 CTL+APO 组之间无差异。DM 组血清抗氧化酶谷胱甘肽过氧化物酶、超氧化物歧化酶（SOD）和过氧化氢酶的活性低于 CTL 组；白藜芦醇恢复了 DM+APO 中的过氧化氢酶和 SOD 水平。各组心肌 NADPH 氧化酶活性无差异。
尽管糖尿病大鼠心肌 NADPH 氧化酶活性无变化，白藜芦醇仍能恢复血清抗氧化酶活性。
