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目的探讨S1P/S1P1信号通路在糖尿病心肌病大鼠心肌损伤中的作用与机制。方法 40只SD大鼠分为正常对照组和2型糖尿病心肌病,每组各20只,链脲佐菌素(streptozotocin,STZ)诱导老鼠建立2型DCM模型,STZ处理8周后,给予老鼠S1P1受体激动剂、S1P1受体拮抗剂干预,观察S1P1受体激动剂、S1P1受体拮抗剂对DCM心肌损伤的影响;HE染色检测心肌组织病理改变,免疫印迹法检测心肌组织Sphk1和S1P1的表达,ELISA法检测组织匀浆液S1P的表达,组织Sph K1激酶活性定量检测试剂盒测定Sph K1酶活性。结果与正常对照组比较,DCM组大鼠心脏凋亡增多、心肌肥大,同时Sph K1及其产物S1P表达增加,S1P1受体下调,S1P1受体拮抗剂干预加重DCM心肌损伤,而S1P1受体激动剂能减轻心肌凋亡、心肌肥大、胶原沉积等。结论 S1P/S1P1信号通路被抑制可能是DCM心肌损伤的机制之一,调控该通路可能是DCM心肌损伤的防治靶点。
Objective To investigate the role and mechanism of S1P / S1P1 signaling pathway in myocardial injury in diabetic cardiomyopathy rats. Methods Forty Sprague-Dawley rats were divided into normal control group and diabetic cardiomyopathy group (n = 20). Twenty rats in each group were induced by streptozotocin (STZ). Two weeks after STZ treatment, S1P1 receptor antagonist and S1P1 receptor antagonist to observe the effect of S1P1 receptor antagonist and S1P1 receptor antagonist on DCM myocardial injury. HE staining was used to detect the pathological changes of myocardial tissue. Western blotting was used to detect the expression of Sphk1 and S1P1 The expression of S1P in tissue homogenate was detected by ELISA. Sph K1 enzyme activity was measured by Sph K1 kinase activity quantitative detection kit. Results Compared with the normal control group, the cardiac apoptosis and cardiac hypertrophy were increased in DCM group, while Sph K1 and its products S1P expression increased, S1P1 receptor decreased, S1P1 receptor antagonist increased DCM myocardial injury, while S1P1 receptor activation Agents can reduce myocardial apoptosis, myocardial hypertrophy, collagen deposition and so on. Conclusion The inhibition of S1P / S1P1 signaling pathway may be one of the mechanisms of myocardial injury in DCM. Regulating this pathway may be the target of preventing and treating DCM myocardial injury.