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促红细胞生成素衍生肽抑制小鼠糖尿病心肌病损伤的作用研究(PDF)

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2017年第4期
页码:
389-393,410
栏目:
基础研究
出版日期:
2017-02-25

文章信息/Info

Title:
Helix B surface peptide attenuates injury of mouse diabetic cardiomyopathy and possible mechanism
作者:
林 晨; 司 瑞; 胡健强; 张国勇; 高蓓蕾; 徐臣年; 郭文怡
第四军医大学西京医院心内科，陕西 西安 710032
Author(s):
LIN Chen;  SI Rui;  HU Jian-qiang;  ZHANG Guo-yong;  GAO Bei-lei;  XU Chen-nian;  GUO Wen-yi
Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi, China
关键词:
促红细胞生成素衍生肽; 糖尿病心肌病; 细胞凋亡; 蛋白激酶B; 糖原合成酶激酶3β
Keywords:
helix B-surface peptide;  diabetic cardiomyopathy;  apoptosis;  Akt;  GSK3β
分类号:
R54
DOI:
-
文献标识码:
A
摘要:
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≥16.7 mmol/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 30 μg/(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。
Abstract:
AIM To observe the protective effects and mechanism of Helix B surface peptide (HBSP) for the injury of mouse diabetic cardiomyopathy. METHODS Eighty male Kunming mice (20-25 g) were randomly divided into four groups: the control group (n=20), the control+HBSP group ［30 μg/(kg·d), n=20］, the diabetic cardiomyopathy (DCM) group (n=20) and the DCM+HBSP group ［30 μg/(kg·d), n=20］. The mice were intraperitoneally injected with streptozotocin to induce type 1 diabetes. Mice with random blood glucose≥16.7 mmol/L were considered as diabetic mice and they were fed for 12 weeks. Mice with impaired cardiac functions evidenced by echocardiography were chosen as diabetic cardiomyopathy mice and twenty of them were randomly chosen to receive intraperitoneal injection of HBSP ［30 μg/(kg·d)］ for 4 consecutive weeks, grouped as DCM+HBSP group. Cardiac functions were evaluated by echocardiography. Apoptosis of cardiomyocytes was detected by TUNEL and myocardial interstitial fibrosis was evaluated by Sirius red staining. Expressions of Akt, phospho-Akt, GSK3β and phospho-GSK3β were detected by Western blotting. RESULTS Compared with the DCM group, the values of LVEF and LVFS in the DCM+HBSP group were increased while the values of LVESV and LVEDV were decreased (P<0.05) and cardiomyocyte apoptosis was inhibited (P<0.05). Compared with the DCM group, myocardial interstitial fibrosis was reduced in the DCM+HBSP group (P<0.01) and expressions of phospho-Akt and phospho-GSK3β were increased (P<0.05 and P<0.01, respectively). CONCLUSION Helix B surface peptide alleviates myocardial apoptosis, reduces myocardial interstitial fibrosis and improves cardiac function in diabetic cardiomyopathy mice. These protective effects of HBSP may possibly be through the activation of Akt-GSK3β signaling pathway.

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备注/Memo

备注/Memo:
收稿日期：2016-06-17.通讯作者：郭文怡，主任医师，主要从事冠心病介入与临床研究 Email：guowenyi@tom.com 作者简介：林晨，硕士生 Email：156836663@qq.com
更新日期/Last Update: 1900-01-01