RESUMO
Background: The clinical treatment of coronary microvascular dysfunction (CMD) is mainly based on conventional medicine, but the mechanism of the medicine is single and the efficacy is different. Shenmai injection (SMI) has a variety of ingredients, but the effect of SMI on CMD has not been studied. This study investigated the effect of SMI on CMD and its possible mechanism. Methods: The protective effect of SMI on CMD was evaluated in Sprague-Dawley (SD) rats and human umbilical vein endothelial cells (HUVECs). In vivo, forty-five male SD rats were randomly divided into control group (sham group), CMD group (model group), and SMI group (treatment group). Two weeks after SMI intervention, laurate was injected into the left ventricle of rats to construct a CMD model. Blood samples were collected to detect myocardial enzymes, oxidative stress, and inflammatory factors, and the hearts of rats were extracted for histopathological staining and western blot detection. In vitro, a hydrogen peroxide-induced endothelial injury model was established in HUVECs. After pretreatment with SMI, cell viability, oxidative stress, vasodilative factors, and apoptosis were detected. Results: In vivo, pretreatment with SMI could effectively reduce the concentrations of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), endothelin-1 (ET-1), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and malondialdehyde (MDA) in the serum of rats. Meanwhile, the expression of bcl-2-associated X (Bax) and caspase-3 protein in the myocardium of rats was decreased in the SMI group. The levels of nitric oxide (NO) and superoxide dismutase (SOD) and the expression of B-cell lymphoma-2 (Bcl-2) were higher in the SMI group than in the CMD group. Pathological staining results showed that SMI could effectively reduce inflammatory infiltration and the formation of collagen fibers and microthrombus in the rat myocardium. In vitro, intervention with SMI could improve endothelial function in a dose-dependent manner as evidenced by increasing the activity of endothelial cells and the expression of NO, SOD, endothelial nitric oxide synthase (eNOS), and Bcl-2, while decreasing cell apoptosis and the levels of ET-1, MDA, Bax, and caspase-3. Conclusions: Pretreatment with SMI could improve CMD by alleviating oxidative stress, inflammatory response, and apoptosis and then improving vascular endothelial function and microvascular structure.
RESUMO
OBJECTIVE: To explore the effect of Musk Tongxin Dropping Pill (MTDP) on myocardial remodeling and microcirculation dysfunction in diabetic cardiomyopathy (DCM). METHODS: Forty male SD rats were randomly divided into control group (control group, n = 10), DCM model group (DCM group, n = 10), DCM model + pioglitazone group (DCM + PLZ group, n = 10), and DCM model + MTDP group (DCM + MTDP group, n = 10). An intraperitoneal single injection of 65 mg/kg streptozotocin (STZ) was used to establish rat model of DCM and the rats in control group were treated with the same dose of sodium citrate buffer solution. DCM + PLZ group was treated with 3 mg/kg/d PLZ by ig after modeling, DCM + MTDP group was treated with 22 mg/kg/d MTDP by ig, and DCM group was treated with 2 ml/kg/d sodium carboxymethyl cellulose (CMC-Na) by ig. The general condition of rats was continuously observed. After intervening for 3 weeks, the random blood glucose of rats was detected by tail vein, and the echocardiography examination was performed. Blood specimens were collected from the abdominal aorta, serum nitric oxide (NO) and endothelin-1 (ET-1) were detected to estimate endothelial function, and tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), IL-1ß, malondialdehyde (MDA), and superoxide dismutase (SOD) were detected to observe the changes of inflammation and oxidative stress indexes. The heart mass index (HMI) was calculated through the ratio of heart mass (HM) to the corresponding body mass (BM). Myocardial pathological tissue staining was performed. RESULTS: Compared with control group, blood glucose in other three groups was higher. Left ventricular end systolic diameter (LVSD) and left ventricular end diastolic diameter (LVDD) in DCM group showed a significant increase, while left ventricular ejection fraction (LVEF) and heart rate (HR) in this group displayed an obvious decrease (P < 0.01). BM and HM in DCM group exhibited a reduction, and HM/BM × 103 revealed an apparent increase (P < 0.01). The levels of serum NO and SOD were distinctly downregulated (P < 0.01), and the levels of ET-1, MDA, TNF-α, IL-1ß, and IL-6 were remarkably upregulated (P < 0.01). Compared with DCM group, a significant decrease was observed in LVSD and LVDD in DCM + MTDP group, while LVEF and HR obviously increased (P < 0.05). BM and HM indicated an apparent increase, but HM/BM ×103 reduced distinctly (P < 0.01). The levels of serum NO and SOD were markedly upregulated (P < 0.05), and the levels of ET-1, MDA, TNF-α, IL-1ß, and IL-6 were significantly downregulated (P < 0.05). HE staining showed that myocardial cells arranged neatly in the control group but not in the DCM group. The intercellular space between myocardial cells in DCM group increased, accompanied by damage of myocardial fibers and infiltration of inflammatory cells. Masson staining displayed an increase in interstitial collagen fibers in DCM group. Carstairs staining showed that microembolization occurred in the myocardium in DCM group, while in DCM + MTDP and DCM + PLZ groups the corresponding myocardial pathological changes were significantly improved. CONCLUSIONS: MTDP might show a positive effect on myocardial remodeling and microcirculation dysfunction in DCM rats.