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. 2020 Oct;24(19):11283-11293.
doi: 10.1111/jcmm.15695. Epub 2020 Sep 2.

QiShenYiQi pill improves the reparative myocardial fibrosis by regulating autophagy

Shichao Lv  1   2 , Peng Yuan  1 , Jianping Dong  3 , Chunmiao Lu  4 , Meng Li  1 , Fan Qu  1 , Yaping Zhu  1 , Zhuo Yuan  1 , Junping Zhang  1
Affiliations

QiShenYiQi pill improves the reparative myocardial fibrosis by regulating autophagy

Shichao Lv et al. J Cell Mol Med. 2020 Oct.

Abstract

QiShenYiQi pill (QSYQ), a traditional Chinese medicine, is well known for improving the myocardial remodelling, but the dose-effect relationship of its intervention in the reparative myocardial fibrosis is still unclear. We investigated the effect of QSYQ on the reparative myocardial fibrosis in cardiac myosin-induced rats and explored its mechanism of action by regulating autophagy. The results indicated that QSYQ increased LVEF and LVFS, and decreased the LVEDD, LVESD, HMI, LVMI, myocardial inflammation histology score, and collagen volume fraction in a dose-dependent manner. In addition, QSYQ declined the number of autophagosomes, down-regulated the expression of myocardial Beclin-1 and LC3B, up-regulated the expression of myocardial p62 and increased the ratios of myocardial p-PI3K/PI3K, p-Akt/Akt and p-mTOR/mTOR. We provided evidence for that QSYQ could inhibit excessive myocardial autophagy by regulating the PI3K/Akt-mTOR pathway and can be a potential therapeutic approach in treating the cardiovascular diseases such as myocarditis and dilated cardiomyopathy.

Keywords: PI3K/Akt-mTOR pathway; autophagy; reparative myocardial fibrosis; traditional Chinese medicine.

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Conflict of interest statement

The authors declare no competing interests.

Figures

FIGURE 1
FIGURE 1
The flow diagram of experiment
FIGURE 2
FIGURE 2
Effect of QiShenYiQi pill (QSYQ) on heart structure and function in rat. A, Echocardiography of rat heart. B, Left ventricular end diastolic diameter in rats. C, Left ventricular end systolic diameter in rats. D, Left ventricular ejection fraction in rats. E, Left ventricular fractional shortening in rats. F, Left ventricular End‐diastolic posterior wall thickness in rats. G, Heart rate in rats. Groups: control (n = 8), model (n = 8), 3‐MA (n = 8), QSYQ‐L (n = 8), QSYQ‐M (n = 8), QSYQ‐H (n = 8). Data are expressed as mean ± SD. *P < 0.01, # P < 0.05
FIGURE 3
FIGURE 3
Effect of QiShenYiQi pill (QSYQ) on the general shape of rat heart. A, General morphology of rat heart. B, Heart mass index of rats. C, Left ventricular mass index of rats. Groups: control (n = 8), model (n = 8), 3‐MA (n = 8), QSYQ‐L (n = 8), QSYQ‐M (n = 8), QSYQ‐H (n = 8). Data are expressed as mean ± SD. *P<0.01, # P < 0.05
FIGURE 4
FIGURE 4
Effect of QiShenYiQi pill (QSYQ) on myocardial histology in rats. A, Representative photomicrograph of haematoxylin and eosin (H&E) staining of myocardium. B, Representative photomicrograph of mason trichrome staining of myocardium. C, The inflammation with a histological score for each group. D, The collagen volume fraction for each group. Data are expressed as mean ± SD. *P < 0.01, # P < 0.05
FIGURE 5
FIGURE 5
Effect of QiShenYiQi pill (QSYQ) on myocardial autophagy in rats. Transmission electron microscopy images of autophagosomes in myocardial. Arrows indicate autophagosomes
FIGURE 6
FIGURE 6
Effect of QiShenYiQi Pill (QSYQ) on mRNA expression of Beclin‐1, LC3B and p62 in rats. A, The Beclin‐1 mRNA expression for each group. B, The LC3B mRNA expression for each group. C, The p62 mRNA expression for each group. Data are expressed as mean ± SD. *P < 0.01, # P < 0.05
FIGURE 7
FIGURE 7
Effect of QiShenYiQi Pill (QSYQ) on the protein expression of Beclin‐1, LC3‐II, LC3‐I and p62 in rats. A, Beclin‐1, LC3‐II, LC3‐I and p62 expression in the myocardium of rats in each group was detected by Western blot. B, The relative protein level of Bcelin‐1 in the myocardium. C, The relative protein level of LC3‐II/LC3‐I in the myocardium. D, The relative protein level of p62 in the myocardium. Data are expressed as mean ± SD. *P < 0.01, # P < 0.05
FIGURE 8
FIGURE 8
Effect of QiShenYiQi Pill (QSYQ) on the main molecules of PI3K / Akt‐mTOR pathway. A, The protein in the myocardium of rats in each group was detected by Western blot. B, The relative protein level of PI3K in the myocardium. C, The relative protein level of p‐PI3K/PI3K in the myocardium. D, The relative protein level of AKT in the myocardium. E, The relative protein level of p‐AKT/AKT in the myocardium. F, The relative protein level of mTOR in the myocardium. G, The relative protein level of pmTOR/ mTOR in the myocardium. Data are expressed as mean ± SD. *P<0.01, #P<0.05.
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