动物造模,心肌缺血再灌注 z-bio 2022-07-08 368

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

　　Methods Curcumin nanoemulsions (CUR-NMs) were prepared and morphologically characterized by transmission electron microscopy; a rat model of myocardial ischemia-reperfusion was established by ligation of the left anterior descending coronary artery, and the rats were randomly divided into sham operation group and model group. group, CUR-treated group and CUR-NMs-treated group, CUR-treated group and CUR-NMs-treated group were pretreated by intraperitoneal injection of CUR (20 mg/kg) and CUR-NMs (20 mg/kg) 4 h before ischemia, respectively. The model group was pretreated with an equal volume of solvent; the hemodynamic changes of the rats in each group were detected; TUNEL staining was used to detect the apoptosis of rat cardiomyocytes; kits were used to detect the levels of CK, LDH, MDA and SOD; Changes in protein expression of calpastatin, Bcl-2 and cleaved-caspase 3.

　　RESULTS The prepared CUR-NMs were uniform in size and round in shape, with a particle size of (121±23) nm. LVDP, +dp / dtmax and -dp / dtmax in the model group were significantly decreased after 30 minutes of ischemia and 2 hours of perfusion (P<0.01), serum LDH, CK and MDA were significantly increased, and SOD was significantly increased. Compared with the model group, the LVDP, +dp / dtmax and -dp / dtmax of the CUR treatment group and the CUR-NMs treatment group were increased in different degrees (P < 0.05 or P < 0. 01), LDH, CK, MDA decreased significantly, SOD increased significantly (P < 0. 05 or P < 0. 01); dtmax and -dp / dtmax increased more (P<0.01), LDH, CK, MDA decreased, SOD increased (P<0.05 or P<0.01). Compared with the sham operation group, the myocardial cell apoptosis was significantly increased in the model group (P<0.01), the protein expressions of calpain1 and cleaved-caspase 3 were significantly up-regulated, and the protein expressions of Bcl-2 and calpastatin were significantly down-regulated (P<0.01). ;Compared with the model group, the apoptosis of cardiomyocytes in the CUR-treated group and the CUR-NMs-treated group was significantly reduced (P<0.01), the protein expressions of calpain1 and cleaved-caspase 3 were significantly down-regulated, and the protein expressions of Bcl-2 and calpastatin were significantly up-regulated (P < 0. 05 or P < 0. 01); Compared with the CUR treatment group, the cardiomyocyte apoptosis in the CUR-NMs treatment group was significantly reduced ( P < 0. 01) calpain1 and cleaved-caspase 3 protein expressions were down-regulated, Bcl -2 and calpastatin protein expressions were 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; the effect may be related to the enhancement of cellular uptake and the inhibition of calpain1 protein expression and activity.