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目的探讨促红细胞生成素衍生肽又称螺旋B表面肽(helix B surface peptide,HBSP)在糖尿病小鼠心肌病中的保护作用及其可能机制。方法 80只(20~25)g雄性昆明小鼠随机分为对照组(n=20)、对照+HBSP组(n=20)、糖尿病心肌病(DCM)组(n=20)、DCM+HBSP组(n=20)。链脲佐菌素(STZ)对小鼠腹腔注射诱导1型糖尿病,最后1次STZ注射完成后第5日,血糖仪检测小鼠尾静脉血葡萄糖水平,3次测量随机血糖均≥16.7mmol/L的视为糖尿病小鼠。糖尿病小鼠继续喂养12周,小动物超声检测提示心功能减退的为DCM小鼠。从中随机选出20只,腹腔注射HBSP 30μg/(kg·d),连续4周,为DCM+HBSP组。采用小动物超声分别检测各组小鼠心功能,TUNEL法检测各组小鼠心肌组织细胞凋亡率,天狼星红染色观察各组小鼠的心肌纤维化程度,Western blot检测心肌组织Akt、p-Akt、GSK3β和p-GSK3β的表达。结果与DCM组相比,DCM+HBSP组左室射血分数[LVEF(%)]及左室短轴缩短率[[LVFS(%)]增加(P<0.05),左心室收缩末期容积(LVESV)和左心室舒张末期容积(LVEDV)降低(P<0.05)、心肌组织细胞凋亡率降低(P<0.05)、心肌纤维化程度减少(P<0.01)、p-Akt表达增加(P<0.05),p-GSK3β的表达增加(P<0.01)。结论 HBSP能够抑制小鼠DCM心肌细胞凋亡、减轻心肌间质纤维化、改善心功能,Akt-GSK3β通路的激活可能参与了HBSP减轻小鼠DCM损伤的保护作用。
Objective To investigate the protective effect of erythropoietin-derived peptide (HBSP) on cardiomyopathy in diabetic mice and its possible mechanism. Methods Eighty male Kunming mice were randomly divided into control group (n = 20), control + HBSP group (n = 20), diabetic cardiomyopathy group (n = 20), DCM + HBSP Group (n = 20). Streptozotocin (STZ) induced type 1 diabetes in mice by intraperitoneal injection. On the 5th day after the last injection of STZ, glucose level in tail vein of mice was measured by glucose meter. The blood glucose of three times was ≥16.7mmol / L as diabetic mice. Diabetic mice were fed for another 12 weeks, and small animal ultrasound examination revealed DCM in DCM patients. Twenty rabbits were randomly selected and intraperitoneally injected with HBSP 30μg / (kg · d) for 4 weeks, which was the DCM + HBSP group. The heart function of mice in each group was detected by small animal ultrasound. The myocardial apoptosis rate was detected by TUNEL method. The myocardial fibrosis was observed by Sirius red staining. The expressions of Akt, p- Akt, GSK3β and p-GSK3β expression. Results Compared with DCM group, left ventricular ejection fraction [LVEF (%)] and left ventricular fractional shortening [[LVFS (%)] increased in DCM + HBSP group (P <0.05). The apoptosis rate of myocardial tissue decreased (P <0.05), the degree of myocardial fibrosis decreased (P <0.01) and the expression of p-Akt increased (P <0.05) ), p-GSK3β expression increased (P <0.01). Conclusion HBSP can inhibit cardiac myocyte apoptosis, relieve myocardial interstitial fibrosis and improve cardiac function in mice. Activation of Akt-GSK3β pathway may be involved in the protective effect of HBSP on DCM injury in mice.