动物实验,姜黄素纳米乳,心肌缺血再灌注 z-bo 2020-09-14 357

　　Objective To construct a curcumin (CUR) nanoemulsion drug delivery system and study its protective effect and mechanism of myocardial ischemia-reperfusion in rats.

　　Methods Curcumin nanoemulsions (CUR-NMs) were prepared and characterized by transmission electron microscopy; the rat myocardial ischemia reperfusion model was established by ligation of the left anterior descending coronary artery, and the rats were randomly divided into sham operation group and model Group, CUR treatment group and CUR-NMs treatment group, CUR treatment group and CUR-NMs treatment group were intraperitoneally injected with CUR (20 mg/kg) and CUR-NMs (20 mg/kg) 4 hours before ischemia. The model group was pretreated with an equal volume of solvent; the hemodynamic changes of rats in each group were detected; TUNEL staining was used to detect the apoptosis of rat myocardial cells; the kit was used to detect the levels of CK, LDH, MDA and SOD; the western blot test was used to detect myocardial calpain1. Changes in the protein expression of calpastatin, Bcl-2, and cleaved-caspase 3.

　　Result The prepared CUR-NMs are uniform in size, round in shape, and have a particle size of (121±23) nm. The LVDP, +dp / dtmax and -dp / dtmax indexes of rats in the model group were significantly decreased (P<0.01) after 30 minutes of ischemia and then loosened and perfused for 2 hours. The serum LDH, CK, and MDA were significantly increased, and SOD was significantly increased. Decrease (P<0.01); Compared with the model group, the LVDP, +dp/dtmax and -dp/dtmax of rats in the CUR treatment group and CUR-NMs treatment group all increased to varying degrees (P<0.05 or P<0.01), LDH, CK, MDA decreased significantly, SOD significantly increased (P<0.05 or P<0.01); compared with CUR treatment group, CUR-NMs treatment group LVDP, +dp/ dtmax and-dp / dtmax increased significantly (P<0.01), LDH, CK, MDA decreased, and SOD increased (P<0.05 or P<0.01). Compared with the sham operation group, the apoptosis of cardiomyocytes in the model group was significantly increased (P<0.01), the expression of calpain1 and cleaved-caspase 3 protein was significantly up-regulated, and the expression of Bcl-2 and calpastatin protein was significantly down-regulated (P<0.01) Compared with the model group, cardiomyocyte apoptosis was significantly reduced in the CUR treatment group and CUR-NMs treatment group (P<0.01), the expression of calpain1 and cleaved-caspase 3 protein was significantly down-regulated, and the protein expression of Bcl-2 and calpastatin was significantly up-regulated (P<0.05 or P<0.01); Compared with CUR treatment group, CUR-NMs treatment group cardiomyocyte apoptosis was significantly reduced (P<0.01) calpain1 and cleaved-caspase 3 protein expression was down-regulated, Bcl -2 and calpastatin protein expression was up-regulated (P<0.05 or P<0.01).

　　Conclusion CUR-NMs can improve myocardial ischemia-reperfusion injury in rats, and the effect is better than CUR; this effect may be related to the enhancement of cell uptake and inhibition of calpain1 protein expression and activity.