Journal of Jilin University(Medicine Edition) ›› 2022, Vol. 48 ›› Issue (2): 399-406.doi: 10.13481/j.1671-587X.20220217

• Research in basic medicine • Previous Articles     Next Articles

Protective effect of antimicrobial peptide LL-37 on myocardial injury in rats with diabetic cardiomyopathy and its mechanism

Chunyan WU1,Jianying WANG2,Haiyan ZENG3(),Shaowen TAN1   

  1. 1.Department of Cardiovascular Medicine,Third Affiliated Hospital,South China University,Hengyang 421900,China
    2.Department of Neurology,Third Affiliated Hospital,South China University,Hengyang 421900,China
    3.Department of Cardiovascular Medicine,Second Affiliated Hospital,South China University,Hengyang 421001,China
  • Received:2021-07-14 Online:2022-03-28 Published:2022-05-10
  • Contact: Haiyan ZENG E-mail:xtgz8837@163.com

Abstract: Objective

To investigate the effect of antibacterial peptide LL-37 on the myocardial injury in the diabetic cardiomyopathy (DCM) rats, and to elucidate its possible mechanism.

Methods

A total of 48 SD rats were randomly divided into normal control group, model group, low dose of LL-37 group (0.5 mg·kg-1) and high dose of LL-37 group(2.0 mg·kg-1),with 12 rats in each group. Except for normal control group, the rats in other groups were fed with high-fat diet combined with intraperitoneal injection of streptozotocin (STZ) to establish the DCM models. After the models were successfully established, the LL-37 drug intervention was performed in low and high doses of LL-37 groups, once a day for 6 weeks. The body weights and fasting blood glucose (FBG) levels of the rats in various groups were monitored; the serum total cholesterol (TC) and triglyceride (TG) levels of the rats in various groups were detected. Cardiac ultrasonography was used to detect the cardiac function of the rats.The pathomorphology of myocardium tissue of the rats in various groups were observed by HE staining. TUNEL staining was used to detect the apoptotic rates of myocardial cells of the rats in various groups. The levels of inflammatory cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in myocardium tissue of the rats in various groups were detected by ELISA. The expression levels of Toll-like receptor 4 (TLR4), nuclear factor kappa B p65 (NF-κB p65) and NF-κB inhibitor α(IκBα) proteins in myocardium tissue of the rats in various groups were detected by Western blotting method.

Results

Compared with normal control group, the myocardial injury of the rats in model group was serious,the left ventricular ejection fraction (LVEF),the left ventricular fractional shortening(LVFS) and the body weight were significantly decreased (P<0.05),the left ventricular end diastolic diameter (LVEDd),the left ventricular end systolic diameter (LVEDs),the levels of FBG, TC, TG and the apoptotic rate of myocardial cells were significantly increased (P<0.05),the levels of IL-1β, IL-6 and TNF-α and the expression levels of TLR4 and NF-κB p65 proteins in myocardium tissue of the rats were significantly increased (P<0.05), while the expression level of IκBα protein was significantly decreased (P<0.05). Compared with model group and low dose of LL-37 group, the myocardial injury of the rats in high dose of LL-37 group was significantly improved,the LVEF, LVFS and the body weight were significantly increased (P<0.05), while the LVEDd, LVEDs, the levels of FBG, TC, TG and the apoptotic rates of myocardial cells were significantly decreased (P<0.05), the levels of IL-1β, IL-6 and TNF-α and the expression levels of TLR4 and NF-κB p65 proteins in myocardium tissue were significantly decreased (P<0.05), while the expression level of IκBα protein was significantly increased (P<0.05). Compared with model group, there were no significant changes in all above indexes in low dose of LL-37 group (P>0.05).

Conclusion

Antimicrobial peptide LL-37 can improve the cardiac function of DCM rats, inhibit the inflammation of myocardium tissue and apoptosis, protect the myocardial injury, and inhibit the activation of TLR4/NF-κB signaling pathway.

Key words: Diabetic cardiomyopathy, Myocardial injury, Antibacterial peptide LL-37, Toll-like receptor 4, Nuclear factor-kappa B

CLC Number: 

  • R285.5