ABSTRACT
Aim To investigate the protective effect of curcumin nanoparticles ( Cur-NPs) against high-fat-in-duced cardiomyocyte injury. Methods H9c2 cardio-myocytes were stimulated with palmitic acid ( PA) to establish a rat model of lipotoxicity injury. The Cur-NPs were pretreated. MTT assay was used to detect cell proliferation. The reactive oxygen species ( ROS) kit was used to detect intracellular reactive oxygen spe-cies and the cells were detected with the TUNEL kit. Apoptosis was detected by Western blot, and the ex-pression levesl of endoplasmic reticulum stress and ap-optotic signaling pathway related proteins were deter-mined. Results High fat might cause the decrease of cell proliferation rate. The level of ROS obviously in-creased, and the pathological changes of cell morphol-ogy were evident. Apoptosis was obviously aggravated. The expression of GRP78, CHOP and caspase-3 appar-ently increased, and the Bax/Bcl-2 ratio elevated, which could all be reversed by Cur-NPs. Conclusions Cur-NPs significantly reduces the production of ROS induced by hyperlipidemia and reduces the expression of endoplasmic reticulum stress and apoptosis-related proteins in cardiomyocytes, thereby inhibiting the dam-age of H9c2 cardiomyocytes induced by high fat.
ABSTRACT
Aim To investigate the role of TGF-β/Smads signaling pathway in the improvement of myo-cardial fibrosis in diabetes mellitus by curcumin. Methods A model of type 2 diabetes mellitus was in-duced by intraperitoneal injection of small dose of streptozotocin (STZ) 35 mg·kg-1with a high glucose and high fat diet, and then intervened by drinking of 300 mg·kg·d-1curcumin. The expression of myo-cardial collagen in rats was detected by Sirius red stai-ning. The expressions of Collange I and Collagen III in myocardium of rats were detected by immunofluores-cence. Cardiac fibroblasts(CFs) in neonatal rats were stimulated by different concentrations of glucose(5.5, 20,25, 30, 35, 50 mmol·L-1) for 24 h to deter-mine the optimum concentration of high glucose model, and rat CFs were stimulated for 24 h by 30 mmol·L-1 high glucose plus different concentrations of curcumin (10,25,50,100,200 μmol·L-1) to determine the optimal concentration of curcumin. The expressions of type Ⅰ and Ⅲ collagen,TGF-β1,p-Smad2,Smad2, p-Smad3,Smad3 and TβR-Ⅲin CFs were detected by Western blot. Results Compared with the control rats,the collagen deposition in the myocardium of the diabetic rats was more obvious and the expression of Collagen Ⅰ and Collagen Ⅲ significantly increased. After treatment of curcumin,the collagen deposition in the myocardium and the expression of Collagen I and CollagenⅢof diabetic rats remarkably decreased. The CFs under the condition of 30 mmol·L-1high glucose and 24 h had the highest survival rate (P <0.05);10μmol·L-1curcumin could obviously inhibit the proliferation of myocardial fibroblasts induced by high glucose (P<0.05). After induced by 30 mmol·L-1 high glucose for 24 h, the expression of Collagen Ⅰand Collagen Ⅲ, TGF-β1, p-Smad2, Smad2, p-Smad3,Smad3 and TβR-Ⅲ proteins in CFs markedly increased(P <0.05), and the expression levels of these proteins were obviously reduced when treated with 25 μmol·L-1curcumin. Conclusion Curcumin could ameliorate myocardial fibrosis in diabetic rats through TGF-β/Smads signaling pathway, exerting the protective effect on myocardium in diabetic rats.
ABSTRACT
Diabetic cardiomyopathy (DCM) is one of the major cardiovascular complications of diabetes mellitus. Currently, there is a lack of effective treatment for DCM,and its pathophys-iology is quite complex. Mitochondria are the main source of car-diomyocyte energy and play an important role in regulating ener-gy metabolism. Mitochondria are swollen and fragmented in dia-betic patients, leading to impaired mitochondrial function, sug-gesting that mitochondrial damage and dysfunction may play an important role in the pathogenesis of DCM. In this paper, the relationship between mitochondrial damage and the pathogenesis of DCM was reviewed from the aspects of abnormal mitochondrial energy metabolism,mitochondrial oxidative stress enhancement, mitochondrial kinetics,mitochondrial heart lecithin change,and mitochondrial calcium disorder.