动物造模,心肌缺血再灌注 z-bio 2022-03-21 701

　　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 treatment group and CUR-NMs treatment group, CUR treatment group and CUR-NMs treatment 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 to 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.