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目的 :探讨促红细胞生成素(erythropoietin,EPO)保护糖尿病大鼠心功能的相关机制。方法:雄性SD大鼠40只,随机分为正常对照组、正常+EPO干预组、糖尿病组、糖尿病+EPO干预组,每组10只。采用链脲佐菌素腹腔注射建立糖尿病动物模型,建模成功后,给予正常+EPO干预组和糖尿病+EPO干预组大鼠皮下注射EPO 1 000 IU/Kg,正常对照组和糖尿病组皮下注射等量生理盐水,每周1次,共12周。建模前及末次给药后7 d,尾静脉采血,检测血糖、血脂和血常规,超声心动图检测心功能,RT-PCR法分析内质网应激蛋白葡萄糖调节蛋白78(glucose regulated protein78,GRP78)、肌浆网Ca2+-ATP酶(SERCA2a)和EPO受体(EPOR)m RNA表达水平,Western blot技术检测GRP78、SERCA2a和EPOR蛋白表达。结果:正常对照组和正常+EPO干预组之间,心功能、血糖、血脂、血常规、GRP78、SERCA2a和EPOR蛋白表达水平均无明显差别(P>0.05)。与正常对照组和正常+EPO干预组相比,糖尿病组大鼠射血分数及左心室短轴缩短率明显下降(P﹤0.01),血糖和血脂明显升高(P﹤0.01),左心室心肌组织GRP78 m RNA及蛋白表达明显增加(P﹤0.01),SERCA2a和EPOR m RNA及蛋白表达明显减少(P﹤0.01)。与糖尿病组相比,糖尿病+EPO干预组大鼠射血分数及左心室短轴缩短率明显增加(P﹤0.01),左心室舒张末期内径明显减小(P﹤0.05),左心室收缩末期内径明显减小(P﹤0.01),左心室组织GRP78m RNA及蛋白表达明显下降(P﹤0.01),SERCA2a和EPOR m RNA及蛋白表达明显增加(P﹤0.01)。结论:EPO具有保护糖尿病大鼠心功能的作用,其机制可能是减轻心肌内质网应激,增加糖尿病大鼠心肌SERCA2a和EPOR蛋白表达。
Objective: To investigate the mechanism of erythropoietin (EPO) in protecting heart function of diabetic rats. Methods: Forty male SD rats were randomly divided into normal control group, normal + EPO intervention group, diabetic group and diabetic + EPO intervention group, with 10 rats in each group. Diabetic rats were established by intraperitoneal injection of streptozotocin (STZ) .After modeling, the rats in the normal + EPO intervention group and diabetic + EPO intervention group were subcutaneously injected with 1 000 IU / kg of EPO, and the normal control group and the diabetic group were injected subcutaneously The amount of saline, once a week, a total of 12 weeks. Blood samples were taken from the tail vein before and after the last administration to determine the cardiac function by echocardiography. The expression of ERK-78 was detected by RT-PCR. GRP78), sarcoplasmic reticulum Ca2 + -ATPase (SERCA2a) and EPO receptor (EPOR) m RNA expression levels were detected by Western blot, GRP78, SERCA2a and EPOR protein expression. Results: There was no significant difference in the expression of GRP78, SERCA2a and EPOR between the normal control group and the normal + EPO intervention group (P> 0.05). Compared with the normal control group and the normal + EPO intervention group, the ejection fraction and the shortening rate of left ventricular shortening in diabetic rats were significantly decreased (P <0.01), blood glucose and blood lipids were significantly increased (P <0.01), left ventricular myocardium The mRNA and protein expression of GRP78 in tissues increased significantly (P <0.01), while the expression of SERCA2a and EPOR mRNA and protein decreased significantly (P <0.01). Compared with diabetic group, the ejection fraction and shortening of left ventricular shortening in diabetic + EPO group were significantly increased (P <0.01), the diameter of left ventricular end-diastolic was significantly reduced (P <0.05), the diameter of left ventricular end-systolic (P <0.01). The mRNA and protein expression of GRP78m in left ventricular tissue were significantly decreased (P <0.01), the expression of SERCA2a and EPOR mRNA and protein were significantly increased (P <0.01). CONCLUSION: EPO can protect the heart function of diabetic rats. Its mechanism may be to reduce myocardial endoplasmic reticulum stress and increase SERCA2a and EPOR protein expression in diabetic rats.