Leonurine protects cardiac function following acute myocardial infarction through anti‑apoptosis by the PI3K/AKT/GSK3β signaling pathway - PubMed (original) (raw)

Leonurine protects cardiac function following acute myocardial infarction through anti‑apoptosis by the PI3K/AKT/GSK3β signaling pathway

Lin Xu et al. Mol Med Rep. 2018 Aug.

Erratum in

Abstract

Leonurine is a compound derived from Herba leonuri, which has been reported to protect cardiac tissue against ischemic injury via antioxidant and anti‑apoptosis effects. The present study investigated whether these effects may be applied to acute myocardial infarction (MI) and examined the underlying mechanisms of leonurine treatment. A rat model of MI was induced by coronary artery ligation. Leonurine was administered at 15 mg/kg/day by oral gavage following the onset of MI. Rats in the sham group and the saline group were administered with an equal volume of saline. Echocardiography, Masson's trichrome staining, and terminal‑deoxynucleotidyl transferase‑mediated dUTP nick end labeling assays were performed 28 days post MI. The expression of B‑cell lymphoma‑2 and Bax were assessed by western blot analysis and reverse transcription‑quantitative polymerase chain reaction. Phosphoinositide 3‑kinase (PI3K), protein kinase B and glycogen synthase kinase‑3β (GSK3β) protein expression were investigated by western blot analysis. Leonurine significantly alleviated collagen deposition and MI size, inhibited cell apoptosis and improved myocardial function. 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. The results demonstrated that leonurine exerts potent cardio‑protective effects in a rat model of MI by inducing anti‑apoptotic effects by activating the PI3K/AKT/GSK3β signaling pathway.

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Figures

Figure 1.

Figure 1.

Echocardiographic evaluation of left ventricular function, including (A) LVEDD, (B) LVESD and (C) LVEF 28 days after myocardial infarction. The data are expressed as the mean ± standard deviation. *P<0.05 vs. sham, #P<0.05 vs. NS. n=12 in each group. LVESD, left ventricular end-systolic diameter; LVEDD, left ventricular end-diastolic diameter; LVEF, left ventricular ejection fractional; NS, saline group.

Figure 2.

Figure 2.

Infarct size 28 days after myocardial infarction. (A) Representative pictures of left ventricles from each group after Masson's Trichrome staining (magnification, ×10). (B) Infarct size as percentages at 28 days. Infarct size is calculated from the ratio of surface area of infarct wall and the entire surface area of the left ventricle. The data are expressed as the mean ± standard deviation. *P<0.05 vs. sham, #P<0.05 vs. NS. n=6 in each group. NS, saline group.

Figure 3.

Figure 3.

Collagen content 28 days after myocardial infarction. (A) Representative pictures of left ventricles from each group after Masson's Trichrome staining (magnification, ×200). (B) Collagen content as percentages at 28 days. Collagen content is calculated from the ratio of the collagen area to the area of the entire high-power field. The data are expressed as the mean ± standard deviation. *P<0.05 vs. sham, #P<0.05 vs. NS. n=6 in each group. NS, saline group.

Figure 4.

Figure 4.

Cardiomyocyte apoptosis 28 days after myocardial infarction. (A) Immunohistochemistry of TUNEL staining in the border zone (Magnifiaction, ×200). (B) The apoptotic index was quantified at 28 days. The data are expressed as the mean ± standard deviation. *P<0.05 vs. sham, #P<0.05 vs. NS; n=6 in each group. NS, saline group.

Figure 5.

Figure 5.

The level of Bcl-2 and Bax mRNA 28 days after MI. (A) The level of Bcl-2 and (B) Bax mRNA 28 days after MI. The data are expressed as the mean ± standard deviation. *P<0.05 vs. sham, #P<0.05 vs. NS; n=6 in each group. NS, saline group; Bcl-2, B-cell lymphoma 2; MI, myocardial infarction.

Figure 6.

Figure 6.

Representative immunoblots and quantified results of (A) Bcl-2 and Bax, (B) p-PI3K and PI3K, (C) p-AKT and AKT proteins by western blot analysis 28 days after myocardial infarction. The data are expressed as the mean ± standard deviation. *P<0.05 vs. sham, #P<0.05 vs. NS. n=6 in each group. Representative immunoblots and quantified results of (D) p-GSK3β and GSK3β and (E) Caspase3 and Cleaved-caspase3 proteins by western blot analysis 28 days after myocardial infarction. The data are expressed as the mean ± standard deviation. *P<0.05 vs. sham, #P<0.05 vs. NS. n=6 in each group. PI3K, phosphoinositide 3-kinase; GSK3β, glycogen synthase kinase-3β.

Figure 6.

Figure 6.

Representative immunoblots and quantified results of (A) Bcl-2 and Bax, (B) p-PI3K and PI3K, (C) p-AKT and AKT proteins by western blot analysis 28 days after myocardial infarction. The data are expressed as the mean ± standard deviation. *P<0.05 vs. sham, #P<0.05 vs. NS. n=6 in each group. Representative immunoblots and quantified results of (D) p-GSK3β and GSK3β and (E) Caspase3 and Cleaved-caspase3 proteins by western blot analysis 28 days after myocardial infarction. The data are expressed as the mean ± standard deviation. *P<0.05 vs. sham, #P<0.05 vs. NS. n=6 in each group. PI3K, phosphoinositide 3-kinase; GSK3β, glycogen synthase kinase-3β.

Figure 6.

Figure 6.

Representative immunoblots and quantified results of (A) Bcl-2 and Bax, (B) p-PI3K and PI3K, (C) p-AKT and AKT proteins by western blot analysis 28 days after myocardial infarction. The data are expressed as the mean ± standard deviation. *P<0.05 vs. sham, #P<0.05 vs. NS. n=6 in each group. Representative immunoblots and quantified results of (D) p-GSK3β and GSK3β and (E) Caspase3 and Cleaved-caspase3 proteins by western blot analysis 28 days after myocardial infarction. The data are expressed as the mean ± standard deviation. *P<0.05 vs. sham, #P<0.05 vs. NS. n=6 in each group. PI3K, phosphoinositide 3-kinase; GSK3β, glycogen synthase kinase-3β.

Figure 6.

Figure 6.

Representative immunoblots and quantified results of (A) Bcl-2 and Bax, (B) p-PI3K and PI3K, (C) p-AKT and AKT proteins by western blot analysis 28 days after myocardial infarction. The data are expressed as the mean ± standard deviation. *P<0.05 vs. sham, #P<0.05 vs. NS. n=6 in each group. Representative immunoblots and quantified results of (D) p-GSK3β and GSK3β and (E) Caspase3 and Cleaved-caspase3 proteins by western blot analysis 28 days after myocardial infarction. The data are expressed as the mean ± standard deviation. *P<0.05 vs. sham, #P<0.05 vs. NS. n=6 in each group. PI3K, phosphoinositide 3-kinase; GSK3β, glycogen synthase kinase-3β.

Figure 6.

Figure 6.

Representative immunoblots and quantified results of (A) Bcl-2 and Bax, (B) p-PI3K and PI3K, (C) p-AKT and AKT proteins by western blot analysis 28 days after myocardial infarction. The data are expressed as the mean ± standard deviation. *P<0.05 vs. sham, #P<0.05 vs. NS. n=6 in each group. Representative immunoblots and quantified results of (D) p-GSK3β and GSK3β and (E) Caspase3 and Cleaved-caspase3 proteins by western blot analysis 28 days after myocardial infarction. The data are expressed as the mean ± standard deviation. *P<0.05 vs. sham, #P<0.05 vs. NS. n=6 in each group. PI3K, phosphoinositide 3-kinase; GSK3β, glycogen synthase kinase-3β.

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