A Study on the Endoplasmic Reticulum Stress-induced Cardiac Hypertrophy in Adult APPswe/PS1dE9 Transgenic Mice / 现代生物医学进展

ABSTRACT

Objective:The present study was designed to explore the role of ER stress in cardiac hypertrophy of adult APPswe /PS1dE9 transgenic mice.Methods:10 adult APPswe/PS1dE9 transgenic mice and 10 C57BL/6 wild type (WT) mice were divided into the transgenic experimental and control group,WT experimental and control group,respectively,with 5 mice in each group.Experimental groups received a low dose ofIsoproterenol (ISO) (2 mg/kg) once a day for 4 weeks to induce cardiac hypertrophy,while control groups received the same volume of normal saline.After 4 weeks,the mice were anesthetized,followed by,electrocardiogram (ECG) recording and the measurement of the heart rate and body weight before being sacrificed.The heart was dissected out,and the masses of heart and the left ventricle were measured,the left ventricule mass index (LVW/BW) and the whole heart weight ratio (HW/BW) were calculated.HE staining was used to observe the pathological and morphological changes of cardiomyocytes,and Western Blot and immunohistochemistry were used to detect the expressions of ER stress relevant proteins-GRP78,JNK,P-JNK and CaMKII.Results:Compared with WT experimental mice,the ventricular wall in the APPswe/PS1dE9 transgenic experimental mice was apparently hypertrophic after the induction by low doses of ISO,and the HW/BW and the LVW/BW were also significantly increased in the APPswe/PS1dE9 transgenic experimental mice than those in the transgenic control mice,WT experimental and control mice (P＜0.05).HE staining showed that compared with the transgenic control mice,WT experimental and WT control mice,in the adult APPswe/PS1dE9 transgenic experimental mice,the cardiomyocyte diameter was obviously increased,cell density was decreased,the capillary density was decreased,the intercellular substance was increased,and the intercellular space was increased.Western blot showed that the expression of GRP78,p-JNK and CaMKII in the experimental group of adult APPswe / PS1dE9 transgenic mice were significantly higher than those in the transgenic control mice and WT mice (P＜0.05,P＜0.01).There were no significant difference among the control group oftransgenic mice and the two groups of WT mice.Immunohistochemistry showed that the positive rates of GRP78 and CaMKII in the cytoplasm of cardiomyocytes of the APPswe/PS1 dE9 transgenic experimental mice were significantly higher than those of experimental WT mice (80％&40 ％)(P＜0.05),and the expressions in the two control groups were negative.The positive rates of p-JNK and JNK in the APPswe/PS1dE9 transgenic experimental mice were 90％ and 40％ respectively,and the expressions were negative in other three groups.Conclusions:The adult APPswe/PSldE9 transgenic mice are more prone to cardiac hypertrophy than WT mice after the induction with a low dose of ISO.ER stress is involved in the formation of cardiac hypertrophy in adult APPswe/PS1dE9 transgenic mice.