PMID- 32572937
OWN - NLM
STAT- MEDLINE
DCOM- 20210421
LR  - 20210421
IS  - 2284-0729 (Electronic)
IS  - 1128-3602 (Linking)
VI  - 24
IP  - 11
DP  - 2020 Jun
TI  - Simvastatin relieves myocardial ischemia/reperfusion injury in rats through 
      hedgehog signaling pathway.
PG  - 6400-6408
LID - 21538 [pii]
LID - 10.26355/eurrev_202006_21538 [doi]
AB  - OBJECTIVE: The aim of this study was to explore the effect of simvastatin (Sim) 
      on myocardial ischemia/reperfusion (I/R) injury in rats and to elucidate the 
      possible underlying mechanism. Our findings might help to provide a certain 
      reference for the clinical prevention and treatment of myocardial I/R injury. 
      MATERIALS AND METHODS: A total of 60 male Sprague-Dawley (SD) rats were 
      randomized into three groups using a random number table, including: Sham group 
      (n=20), I/R group (n=20) and I/R + Sim group (n=20). The I/R injury model was 
      successfully established in rats via ligation of the left anterior descending 
      coronary artery (LAD), followed by reperfusion. Before operation, the rats in I/R 
      + Sim group were administered with Sim at 10 mg/kg/d through oral gavage for 7 d. 
      Cardiac ejection fraction (EF) (%) and fractional shortening (FS) (%) of rats in 
      each group were detected using echocardiography. 2,3,5-triphenyltetrazolium 
      chloride (TTC) staining was performed to measure the myocardial infarction (MI) 
      area in each group. Collagen deposition in myocardial tissues of rats in each 
      group was detected by Masson's trichrome staining. The apoptosis level of 
      myocardial cells and fibroblasts in myocardial tissues of rats in each group were 
      evaluated via terminal deoxynucleotidyl transferase-mediated dUTP nick end 
      labeling (TUNEL) staining. The level of reactive oxygen species (ROS) in 
      myocardial tissues of rats in each group was determined using fluorescent probes. 
      Reverse Transcription-Polymerase Chain Reaction (RT-PCR) was conducted to measure 
      the expression levels of pro-inflammatory cytokines interleukin (IL)-1beta and 
      monocyte chemoattractant protein-1 (MCP-1) in myocardial tissues of rats in each 
      group. Furthermore, the effects of Sim on the hedgehog signaling 
      pathway-associated proteins were detected using Western blotting. RESULTS: Sim 
      significantly alleviated I/R-induced cardiac dysfunction in rats and increased EF 
      (%) and FS (%) (p<0.05). Meanwhile, it also evidently mitigated the MI caused by 
      I/R and reduced the infarction area (p<0.05). According to the Masson's trichrome 
      staining results, I/R + Sim group exhibited remarkably declined myocardial 
      interstitial collagen deposition compared with I/R group (p<0.05). ROS-sensitive 
      fluorescent staining showed that Sim notably reversed the increase of ROS 
      expression and the decrease of myocardial oxidative stress induced by I/R 
      (p<0.05). Finally, Western blotting results revealed that Sim dramatically 
      restrained the protein expressions of sonic hedgehog (SHH), patched 1 (PTC1) and 
      glioma-associated oncogene homolog 1 (GLI1) (p<0.05). CONCLUSIONS: Sim can 
      significantly relieve myocardial I/R injury in rats. The possible underlying 
      mechanism may be related to its inhibition on the hedgehog signaling pathway.
FAU - Feng, L
AU  - Feng L
AD  - Department of Geriatrics, Zhejiang Provincial People's Hospital, People's 
      Hospital of Hangzhou Medical College, Hangzhou, China. whf850405@126.com.
FAU - Lai, Q-M
AU  - Lai QM
FAU - Zhou, G-M
AU  - Zhou GM
FAU - Yang, L
AU  - Yang L
FAU - Shi, T-Y
AU  - Shi TY
FAU - Jiang, L
AU  - Jiang L
FAU - Wang, H-F
AU  - Wang HF
LA  - eng
PT  - Journal Article
PL  - Italy
TA  - Eur Rev Med Pharmacol Sci
JT  - European review for medical and pharmacological sciences
JID - 9717360
RN  - 0 (Hedgehog Proteins)
RN  - 0 (Reactive Oxygen Species)
RN  - AGG2FN16EV (Simvastatin)
SB  - IM
MH  - Animals
MH  - Dose-Response Relationship, Drug
MH  - Hedgehog Proteins/*antagonists & inhibitors/genetics/metabolism
MH  - Injections, Intraperitoneal
MH  - Male
MH  - Myocardial Reperfusion Injury/*drug therapy/metabolism/pathology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reactive Oxygen Species/analysis/metabolism
MH  - Signal Transduction/drug effects
MH  - Simvastatin/administration & dosage/*pharmacology
EDAT- 2020/06/24 06:00
MHDA- 2021/04/22 06:00
CRDT- 2020/06/24 06:00
PHST- 2020/06/24 06:00 [entrez]
PHST- 2020/06/24 06:00 [pubmed]
PHST- 2021/04/22 06:00 [medline]
AID - 21538 [pii]
AID - 10.26355/eurrev_202006_21538 [doi]
PST - ppublish
SO  - Eur Rev Med Pharmacol Sci. 2020 Jun;24(11):6400-6408. doi: 
      10.26355/eurrev_202006_21538.