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Experimental Study on Reducing High Glucose-Induced Injury in H9c2 Cardiomyocytes by Modulating PI3K/Akt/mTOR Signaling Pathway with Zicui Tongmai Decoction |
WU Gangqiang, YUAN Chunyun, YUAN Sisi, et al |
Affiliated Hospital of Hunan Provincial Institute of Traditional Chinese Medicine / National Famous Old Chinese Medicine Experts Bu Xianchun Inheritance Studio, Hunan Changsha 410006, China |
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Abstract Objective: To investigate the possible signaling pathways (PI3K-Akt-mTOR) involved in autophagy and apoptosis of H9c2 cardiomyocytes induced by high glucose, and to investigate the mechanism of action of Zicui Tongmai Decoction in inhibiting cardiomyocyte apoptosis. Methods: SD rats were randomly divided into blank plasma group and Zicui Tongmai Decoction group, with 10 rats in each group. The corresponding medicated plasma was prepared by gavage for 7 days,the drug concentration of Zicui Tongmai Decoction group was 4.4g/mL and the gavage volume was 10mL·kg-1·d-1,the blank plasma group was gavaged with the same dose of sterilized ultrapure water (the administration volume was 10mL/kg). H9c2 myocardial cells were divided into normal group, blank plasma group and drug containing plasma group, fetal bovine serum, blank plasma and drug containing plasma were added respectively. A concentration gradient of 5%, 10% and 15% was set for each group. The proliferation of H9c2 cardiomyocytes in each group was compared by CCK-8 method, the cell survival rate was calculated, and the drug containing plasma was screened. H9c2 cardiomyocytes induced by high glucose were randomly divided into three groups: model group, Zicui Tongmai Decoction medicated plasma group and engliejing group, and additionally there was normal group. Expression of LC3B in H9c2 cardiomyocytes was detected 24h after administration of IF, and the expression of PI3K Akt mTOR signal pathway protein and apoptosis related protein caspase-3 was detected by Western blot. Results: Drug containing plasma and blank plasma have no significant effect on cell proliferation at the concentration level of 10%, which is used as the intervention concentration of drug containing plasma experiment. The expression of LC3B Ⅱ/LC3BⅠ decreased significantly compared with the normal group(P<0.05),but the protein expression of PI3K, P-Akt, mTOR and Caspase-3 increased compared with the normal group(P<0.05). The expression of LC3B Ⅱ/LC3BⅠin Zicui Tongmai Decoction medicated plasma group and engliejing group increased significantly compared with the model group(P<0.05),but the protein expression of PI3K,P-Akt,mTOR and Caspase-3 in Zicui Tongmai Decoction medicated plasma group and engliejing group decreased compared with the model group(P<0.05). There was no significant difference in expression of LC3BⅡ/LC3BⅠ and protein expression of PI3K,P-Akt,mTOR and Caspase-3 between Zicui Tongmai Decoction medicated plasma group and engliejing group (P>0.05). Conclusion: Zicui Tongmai Decoction can activate autophagy and inhibit apoptosis of cardiomyocytes, which may be related to the inhibition of PI3K/p-Akt / mTOR signaling pathway.
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