Desrois Martine, Lan Carole, Movassat Jamileh, Bernard Monique
Aix-Marseille Université, CNRS, CRMBM, Marseille, France ; Centre de Résonance Magnétique Biologique et Médicale (CRMBM), UMR n°7339, Aix-Marseille Université, CNRS, Faculté de Medecine, 27 Bd Jean Moulin, Marseille Cedex 05, 13385 France.
Aix-Marseille Université, CNRS, CRMBM, Marseille, France.
Nutr Metab (Lond). 2017 Jan 13;14:6. doi: 10.1186/s12986-016-0157-z. eCollection 2017.
Type 2 diabetes is associated with greater relative risk of cardiovascular diseases in women than in men, which is not well understood. Consequently, we have investigated if male and female displayed differences in cardiac function, energy metabolism, and endothelial function which could contribute to increased cardiovascular complications in type 2 diabetic female.
Male and female Control and type 2 diabetic Goto-Kakizaki (GK) isolated rat hearts were perfused during 28 min with a physiological buffer before freeze-clamping for biochemical assays. High energy phosphate compounds and intracellular pH were followed using P magnetic resonance spectroscopy with simultaneous measurement of contractile function. Nitric oxide (NO) pathway and endothelium-dependent and independent vasodilatations were measured as indexes of endothelial function. Results were analyzed via two-way ANOVA, 0.05 was considered as statistically significant.
Myocardial function was impaired in male and female diabetic versus Control groups ( 0.05) without modification of energy metabolism. Coronary flow was decreased in both diabetic versus Control groups but to a higher extent in female GK versus male GK rat hearts ( 0.05). NO production was up-regulated in diabetic groups but to a less extent in female GK rat hearts ( 0.05). Endothelium-dependent and independent vasodilatations were impaired in female GK rat compared with male GK ( 0.05) and female Control ( 0.05) rat hearts.
We reported here an endothelial damage characterized by a reduced up-regulation of the NO pathway and impaired endothelial and smooth muscle functions, and coronary flow rates in the female GK rat hearts while energy metabolism was normal. Whether these results are related to the higher risk of cardiovascular complications among type 2 diabetic female needs to be further elicited in the future.
2型糖尿病女性患心血管疾病的相对风险高于男性，对此人们尚未完全理解。因此，我们研究了雄性和雌性在心脏功能、能量代谢和内皮功能方面是否存在差异，这些差异可能导致2型糖尿病女性心血管并发症增加。
雄性和雌性对照大鼠及2型糖尿病Goto-Kakizaki（GK）大鼠的离体心脏在灌注生理缓冲液28分钟后进行冷冻钳夹，用于生化分析。使用磷磁共振波谱法跟踪高能磷酸化合物和细胞内pH值，同时测量收缩功能。测量一氧化氮（NO）途径以及内皮依赖性和非依赖性血管舒张，作为内皮功能指标。结果通过双向方差分析进行分析，P<0.05被认为具有统计学意义。
与对照组相比，雄性和雌性糖尿病组的心肌功能均受损（P<0.05），能量代谢未改变。糖尿病组与对照组相比，冠状动脉血流量均减少，但雌性GK大鼠心脏的减少程度高于雄性GK大鼠心脏（P<0.05）。糖尿病组中NO生成上调，但雌性GK大鼠心脏的上调程度较小（P<0.05）。与雄性GK大鼠（P<0.05）和雌性对照大鼠（P<0.05）心脏相比，雌性GK大鼠的内皮依赖性和非依赖性血管舒张受损。
我们在此报告，雌性GK大鼠心脏存在内皮损伤，其特征为NO途径上调减少、内皮和平滑肌功能受损以及冠状动脉血流量减少，而能量代谢正常。这些结果是否与2型糖尿病女性心血管并发症风险较高有关，有待未来进一步探讨。
