To observe the effects of Kangxian Yixin Decoction (抗纤益心方, KYD) on cardiomyocyte apoptosis and endoplasmic reticulum stress-related factors glucose regulated protein 78 (GRP78), activating transcription factor 6 (ATF6) and C/EBP homologous protein (CHOP) in mice with dilated cardiomyopathy (DCM), and to explore the mechanism of KYD regulating GRP78/ATF6 signaling pathway to improve the apoptosis of DCM cardiomyocytes.

According to the random number table method, 40 cTnT^R141W transgenic DCM mice were divided into model group, KYD high and low dose (5.4 g/kg, 2.7 g/kg) groups and captopril (0.01 g/kg) group, with 10 mice in each group. Another C57BL/6J mice were set up as the normal group. Left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic diameter (LVEDD), ejection fraction (EF) and reduction rate (FS) were detected by ultrasonography in small animals. Myocardial pathological morphology was observed by HE staining, endoplasmic reticulum ultrastructure was observed by electron microscopy, and myocardial apoptosis was detected by TUNEL method. The expression levels of GRP78 and ATF6 in myocardial tissue of mice were detected by immunohistochemistry (IHC) method. The mRNA and protein expressions of GRP78, ATF6, CHOP, Bax and Bcl-2 were detected by Real-time PCR and Western blot, respectively.

Compared with those in the normal group, the levels of LVESD and LVEDD were increased in the model group, the levels of FS and EF were decreased (P<0.05), myocardial pathological injury and apoptosis number increased (P<0.01), endoplasmic reticulum structure was damaged and enlarged. The expressions of GRP78 and ATF6 were increased by IHC (P<0.05). The mRNA expressions of GRP78, ATF6 and CHOP were increased (P<0.05). The expressions of GRP78, ATF6, CHOP and Bax were increased, while the expression of anti-apoptotic factor Bcl-2 was decreased (P<0.05). Compared with those in the model group, the levels of LVESD and LVEDD were decreased, the levels of FS and EF were increased (P<0.05), myocardial injury was alleviated, the apoptosis was decreased, the endoplasmic reticulum was damaged and enlarged, and IHC results showed that the expressions of GRP78 and ATF6 were decreased (P<0.05、P<0.01) in the KYD groups. The mRNA expressions of GRP78, ATF6 and CHOP were decreased (P<0.05, P<0.01). The expressions of GRP78, ATF6, CHOP and Bax were decreased (P<0.05, P<0.01), while the expressions of anti-apoptotic factor Bcl-2 were increased (P<0.05, P<0.01).

KYD can inhibit DCM cardiomyocyte apoptosis and improve the cardiac function in mice, and its mechanism may be related to inhibiting endoplasmic reticulum stress and down-regulating ATF6/GRP78 signaling pathway.