[Animal modeling]-Preparation of curcumin nanoemulsion and its protective effect on myocardial ischemia and reperfusion in rats

  OBJECTIVE: To construct a curcumin (CUR) nanoemulsion drug delivery system and study its protective effect on myocardial ischemia-reperfusion in rats and its mechanism. The curcumin nanoemulsion (CUR-NM) was prepared by the method and characterized by transmission electron microscopy. The left anterior descending coronary artery was ligated to establish a rat myocardial ischemia-reperfusion model, and the rats were randomly divided into rats. In the sham operation group, model group, CUR treatment group and CUR-NMs treatment group, CUR (20 mg/kg) and CUR-NMs (20 mg/kg) were injected intraperitoneally for 4 hours before ischemia treatment. Each group was pretreated with the same amount of solvent; rat hemodynamic changes in each group; TUNEL method to detect rat cardiomyocyte apoptosis; CK, LDH, MDA, SOD levels; kit to detect cardiac troponin 1, cardiac calcium The protein level was detected by Western blot. , Bcl-2, cleaved caspase 3 protein expression is changed.

  Result: The prepared CUR-NM is uniform in size, round in shape, and particle size (121±23) nm. In the model group, the LVDP, +dp/dtmax and -dp/dtmax indexes of rats in the model group were significantly reduced 30 minutes after ischemia and 2 hours after release perfusion (P\u003c0.01). Serum LDH, CK and MDA increased significantly, and SOD decreased significantly (P\u003c0.01). Compared with the model group, the LVDP group of the CUR and CUR-NMs treatment group, the +dp/dtmax and -dp/dtmax groups all increased to varying degrees (P\u003c0.05 or P\u003c0.01), LDH, CK , MDA was significantly reduced, and SOD was significantly increased (P\u003c0.05 or P\u003c0.01). Compared with the CUR treatment group, the LVDP, +dp/dtmax and -dp/dtmax of the CUR-NMs treatment group increased significantly (P\u003c0.05). 0.01), LDH, CK, MDA decreased, SOD increased (P\u003c0.05 or P\u003c0.01). The apoptosis of cardiomyocytes in the model group was significantly increased (P\u003c0.01), the expression of Carpine 1 and Caspase 3 cleavage protein was significantly increased, Bcl-2 was significantly increased, and the expression of Carpathatin protein was significantly decreased. Compared with the model, the CUR and CUR-NM treatment groups (P\u003c0.01) have proteins cleaved by Carpine 1 and Caspase 3. The expression was significantly down-regulated, and the expression of Bcl-2 and caspase protein was significantly up-regulated (P\u003c0.05 or P\u003c0.01). Compared with the CUR treatment group, the cardiomyocyte apoptosis of the CUR-NMs treatment group was significantly reduced (P\u003c0.01). Calpain1 and cleaved caspase3 protein were down-regulated, and the expression of Bcl-2 and calpastatin protein was up-regulated (P\u003c0.05 or P\u003c0.01).

  Conclusion: CUR-NM can improve myocardial ischemia-reperfusion injury in rats, and its effect is better than CUR. This effect may be related to increasing cell uptake and inhibiting the expression and activity of calpain 1 protein.