内源性大麻素系统在慢性间歇低氧大鼠心肌肥厚病理过程中的作用

The Pathological Processing of Endocannabinoid System on Cardiac Hypertrophy in a Experimental Rats With Chronic Intermittent Hypoxia

目的:探讨内源性大麻素系统在慢性间歇低氧大鼠心肌肥厚中作用及使用内源性大麻素受体拮抗剂利莫那班后对其的影响。方法:48只雄性Wistar大鼠,根据实验设计在实验4、6周时随机分组,即正常对照4周组、6周组,低氧4周组、6周组,低氧+利莫那班即拮抗低氧4周组、6周组,共6组,随机取8只大鼠,处死后测左心室质量指数(LVMI),光学显微镜下观察心肌细胞形态变化,免疫组化测钙/钙调素依赖性蛋白激酶II(CaMKII)、心肌营养素-1(CT-1)表达。结果:低氧4周组、6周组分别与正常对照4周组、6周组相比,LVMI、光镜下心肌细胞肥厚及免疫组化下CaMKII、CT-1均明显升高,组间比较差异均有统计学意义(P<0.001);与正常对照组、低氧组比较,低氧拮抗组上述各项明显高于正常对照组但低于低氧组,各组间比较差异均有统计学意义(P<0.001)。结论:慢性间歇低氧通过导致内源性大麻素系统紊乱诱发心肌肥厚,使用其拮抗剂利莫那班干预后可有效减轻上述病理过程的发生。

Objective： To investigate the effect of endocannabinoid system on cardiac hypertrophy in experimental rats with chronic intermittent hypoxia and to study the impact of endocannabinoid antagonist, rimonabant in such pathological processing. Methods： A total of 48 male Wistar rats were divided into 6 groups. 4 and 6 weeks of Normal control group, 4 and 6 weeks of Hypoxia group, 4 and 6 weeks of Hypoxia with rimonabant intervention group. n=8 in each group. The rats were sacrificed to measure left ventricular mass index （LVMI）, the myocardial cell morphological changes were observed by optical microscope, the expression of cardiac calcium/calmodulin-dependent protein kinase II （CaMKII） and cardiotrophin-1 （CT-1） were detected by immunohistochemistry at 4 and 6 weeks respectively. Results： Compared with 4 and 6 weeks of Normal control group, the LVMI, cardiac hypertrophy condition, CaMKII and CT-1 were increased in 4 and 6 weeks of Hypoxia group, all P〈0.001. Compared with Normal control group and Hypoxia group, the above indexes in Hypoxia with rimonabant intervention group were higher than those in Normal control group while lower than those in Hypoxia group, all P〈0.001. Conclusion： The Chronic intermittent hypoxia could induce myocardial hypertrophy via endocannabinoid system disorders, such pathological processing could be reduced by rimonabant intervention.