One group underwent AMI (n = 22), another AMI and L6-WT sheet transplantation (n = 17), and a third AMI and L6-Bcl2 sheet transplantation (n = 20).Five rats underwent a sham operation.
Using acute myocardial infarction rat models, we found that a combination therapy of CaSR inhibition and embryonic stem cell (ESC) transplantation after acute myocardial infarction (AMI) leads to a dramatic reduction in the infarct size; a significant increase in the maximum rising and falling rate (+dp/dtmax and -dp/dtmax, respectively) of left ventricular pressure; a significant decrease in left ventricular end-diastolic pressure; a significant decrease in the mRNA expression level of CaSR, Bax, Bcl-2, cleaved caspase-3, cleaved caspase-9, p-ERK, p-JNK and p-P38 protein together with apoptosis indexes in the C and E groups; and a significant decrease in cTnT levels as well as LDH and CK activity.
In addition, it suppressed matrix metallopeptidase‑9, transforming growth factor‑β, p38 mitogen‑activated protein kinases (MAPK) and nuclear factor (NF)‑κB protein expression, and promoted B‑cell lymphoma 2 (Bcl‑2) protein expression in AMI mice.
Preventive effect of hesperidin modulates inflammatory responses and antioxidant status following acute myocardial infarction through the expression of PPAR‑γ and Bcl‑2 in model mice.
This was accompanied by significantly increased levels of phosphorylated (p)‑PI3K, p‑AKT, p‑GSK3β and Bcl‑2, as well as significantly decreased levels of caspase3, cleaved‑caspase3 and Bax following MI.
Compared with AMI group and AMI + E group, in the AMI + PLV-PI3KCG group, left ventricular end diastolic diameter (LVEDd) was decreased, left ventricular ejection fraction (LVEF%) was significantly increased, and vascular endothelial growth factor (VEGF) expression was significantly increased in the infarct region (P<0.05); PI3KCG, pAkt/Akt, HIF-1a, and Bcl-2/Bax protein expressions were significantly increased (P<0.05).
Compared with the SO group, Cx43, SOD, and Bcl-2 were decreased, MDA, Bax, caspase-3, TNF-α, IL-6, and HMGB1 were increased in the MI group, and all the alterations were significantly restrained in the LOMD+AMI group.
It was detected via RT-PCR and immunohistochemistry that, compared with those in the Sham group, the expression level of the anti-apoptosis gene B-cell lymphoma 2 (Bcl-2) was substantially decreased, but the expression levels of pro-apoptosis gene Bcl-2 associated X protein (Bax) and the JNK pathway-related JNK and c-Jun were evidently elevated in the AMI group (p<0.05).