Shengmai San preserves myocardial calcium homeostasis by inhibiting CaMKII activity before pathological changes in diabetic mice

Background: Diabetic cardiomyopathy (DCM) is a common heart problem in people with diabetes. It is a big public health problem that needs to be treated effectively. Shengmai San (SMS) can be used to treat diabetic cardiomyopathy, coronary heart disease and heart damage, but it is unclear whether it can protect the calcium balance of diabetic cardiomyopathy in the early stages. Objective: To investigate the regulatory mechanism of SMS on sarcoplasmic reticulum calcium transport in diabetic mice. Methods: 8-week-old db/db mouse models were randomly divided into a diabetic model group (Model), SMS intervention group (SMS) and CaMKⅡ inhibitor group (KN-93). Age-matched db/m mice were used as control group. After 8 weeks of treatment, cardiac function and morphology were assessed, and calcium transients in cardiomyocytes and sarcoplasmic reticulum calcium transport were detected. Western blot was used to detect the expression of CaMKⅡ and proteins related to myocardial calcium transport. Results: In 16-week-old db/db mice, there was no obvious abnormality in myocardial contractile function, the ventricular wall was not thickened, and the cross-sectional area of cardiomyocytes was not significantly enlarged. Compared with the model group, in the SMS group, the calcium transient amplitude was increased, the calcium content of the sarcoplasmic reticulum was upregulated, the calcium elimination time constant was decreased, calcium elimination was accelerated, and the proportion of calcium released from the sarcoplasmic reticulum during the calcium transient was increased. At the same time, SMS could reduce cytosolic free calcium in diabetic mice, and its possible mechanism was to reduce calcium leakage from the sarcoplasmic reticulum, and its effect was similar to that of the KN93 group. The expressions of CaMKII protein and p-CaMKII protein were significantly upregulated in the model group, while SMS could significantly downregulate the expressions of both. Conclusions: SMS can reduce sarcoplasmic reticulum calcium leak and protect the calcium homeostasis of diabetic myocardium. Its mechanism may be by reducing the expression of CaMKII protein and the phosphorylation level of CaMKII protein.