Study on the Combination of Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos to Regulate Unfolded Protein Response and Improve Cardiac Function in Mice with Diabetic Cardiomyopathy

  OBJECTIVE  To explore the effects of oral administration of Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos (DH) on mice with diabetic cardiomyopathy and the underlying mechanisms.

  METHODS  Forty-six C57BL/6J mice were divided into the control (CTL) group, diabetic cardiomyopathy (DCM) group, short-term DH administration (DCM-DHO) group, long-term DH administration (DCM-DHOL) group and empagliflozin positive drug (EMPA) group. A mouse model of diabetic cardiomyopathy was established using a high-fat diet (10 weeks) combined with STZ injection (120 mg·kg^-1, single injection). The body weight, energy intake, and water consumption of mice were monitored and the glucose metabolism of mice was evaluated by oral glucose tolerance test (OGTT) and insulin tolerance test (ITT). Cardiac systolic function (FS) and diastolic function (MV E/A) of mice were measured by echocardiography. Molecular biological methods were used to analyze the gene and protein expression of key transcription factors such as IRE1, PERK, ATF6α, ATF4, Xbp1s, GRP94 and GRP78 in unfolded protein response signal pathway.

  RESULTS  Compared with diabetic cardiomyopathy mice, the water consumption and blood glucose level of DCM-DHOL mice were decreased by 21.56% (P < 0.000 1) and 28.82% (P < 0.000 1), respectively; the insulin level was increased by 43.63% (P < 0.05) and the areas under the curves of OGTT and ITT were decreased by 16.56% (P < 0.05) and 6.82%, respectively; the FS and MV E/A were increased by 32.86% (P < 0.001) and 24.3% (P < 0.01), respectively; the gene expression levels of left ventricular IRE1, Xbp1, GRP78 and GRP94 (P < 0.05) and the protein expression level of GRP78 (P < 0.05) were also significantly increased. In DCM-DHO mice, the water consumption decreased by 10.46% (P < 0.05), cardiac diastolic function MV E/A increased by 17.87% (P < 0.01), and the mRNA levels of IRE1, Xbp1s, GRP78 and GRP94 and protein expression of GRP78 (P < 0.05) were significantly improved as compared with diabetic cardiomyopathy mice.

  CONCLUSION  Oral administration of DH has a significant improvement effect on diabetic cardiomyopathy mice.