Protective effects of phosphodiesterase 5 shRNA on doxorubicin-induced cardiomyopathy in mice
10.13699/j.cnki.1001-6821.2017.14.016
- VernacularTitle:抑制磷酸二酯酶5的短发夹RNA重组腺病毒载体对阿霉素所致心肌病小鼠的保护作用
- Author:
Jin-Wen XIAO
1
;
Long-Hu LI
;
Bing-Zhe HONG
Author Information
1. 大连大学附属中山医院心内科
- Keywords:
doxorubicin;
cardiomyopathy;
phosphodiesterase 5 shRNA;
cardiomyocyte atrophy;
myocardial fibrosis
- From:
The Chinese Journal of Clinical Pharmacology
2017;33(14):1344-1347
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the protective effects of phosphodies terase 5 shRNA [PDE5shRNA] on doxorubicin (DOX)-induced cardiomyopathy in mice.Methods A single intraperitoneal injection of doxorubicin 15 mg · kg-1 to induce cardiomyopathy to establish model.Male 10-week-old C57BL/6J mice were randomly assigned to three groups:model group (n =16);experimental group(DOX + PDE5shRNA,n =16):a single intraperitoneal injection of same dose of doxorubicin and being simultaneously treated with a single myocardial injection of PDE5shRNA 1 x 1010 particles;Normal group (n =10):a single intraperitoneal injection of same volume of saline.After two weeks of administration,left ventricular end-systolic diameter (LVESD),left ventricular end-distolic diameter (LVEDD),left ventricular ejection fraction (LVEF) and percent fractional shortening (％ FS) were evaluated by echocardiography.Cardiac specimens were then subjected for HE (Hematoxyum Eosin),Masson staining,computing for each group of cardiac cell size and fibrosis area.Levels of cyclic guanosine monophosphate (cGMP) and protein kinase G (PKG) in the myocardium were assayed by ELISA.The expression of myosin heavy chain (MHC),Troponin I and Desmin were evaluated by Western blot.Results Two weeks later of administration,indicators in experimental group and model group were as follows:LVESD were(2.13 ±0.10),(2.75 ±0.12)mm;LVEDD were(2.98 ± 0.10),(3.42 ± 0.12) mm;LVEF were (58.74 ± 1.40)％,(48.53 ± 1.50)％;％ FS were (28.52 ± 2.10) ％,(19.59 ± 1.67) ％;the transverse diameter of cardiomyocytes were (14.68 ± 0.42),(13.75 ±0.38)μm;cardiac fibrosis were (2.28 ±0.20)％,(5.10 ±0.35)％;the levels of cGMP expression were (0.23 ± 0.02),(0.06 ± 0.01) pg · mg-1;the levels of PKG were (0.21 ± 0.02),(0.10 ± 0.01) pg · mg-1;the myocardial expression of MHC were 1.55 ± 0.16,1.15 ± 0.22;the expression of troponin I were 1.32 ± 0.08,0.88 ±0.08;the expression of Desmin were 1.327 ± 0.512,1.103 ± 0.038;all the above data were significantly different compared between two groups (all P ＜ 0.05).Conclusion The protective effects of PDE 5shRNA on doxorubicin-induced cardiomyopathy,mitigatting doxorubicin-induced impairment of cardiac function in mice,significantly attenuatting doxorubicin-induced atrophic degeneration of cardiomyocyte and myocardial fibrosis through possible activating cGMP/PKG signaling pathway.
