PMID- 32495900
OWN - NLM
STAT- MEDLINE
DCOM- 20210325
LR  - 20210325
IS  - 2284-0729 (Electronic)
IS  - 1128-3602 (Linking)
VI  - 24
IP  - 10
DP  - 2020 May
TI  - Carbachol alleviates myocardial injury in septic rats through PI3K/AKT signaling 
      pathway.
PG  - 5650-5658
LID - 21356 [pii]
LID - 10.26355/eurrev_202005_21356 [doi]
AB  - OBJECTIVE: To explore the effect of carbachol on myocardial injury in septic 
      rats, and to further study its influence on the phosphatidylinositol 3-kinase 
      (PI3K)/protein kinase B (AKT) signaling pathway. MATERIALS AND METHODS: A total 
      of 48 healthy male Sprague-Dawley rats were randomly divided into sham group 
      (n=16), model group (n=16), and carbachol group (n=16). The rat model of sepsis 
      was established via cecal ligation and puncture. Carbachol was intraperitoneally 
      injected (10 mug/kg) immediately after operation in carbachol group, and no cecal 
      ligation was performed in sham group. At 48 h after operation, the survival rate 
      of rats in each group was recorded, the activity of plasma creatine kinase-MB 
      (CK-MB) was detected, and the cardiac function in each group was determined. 
      Moreover, the heart was isolated, and the myocardial tissues were taken to detect 
      the apoptosis level using the terminal deoxynucleotidyl transferase-mediated dUTP 
      nick end labeling (TUNEL) apoptosis kit. The content of inflammatory factors in 
      myocardial tissues was determined using enzyme-linked immunosorbent assay (ELISA) 
      kits, and the expression levels of apoptosis-related proteins and the PI3K/AKT 
      signaling pathway-related proteins were detected via Western blotting. RESULTS: 
      Carbachol could significantly raise the survival rate of septic rats (p<0.01), 
      remarkably decrease the activity of CK-MB (p<0.01), markedly reduce the left 
      ventricular internal diameter at end-systole (LVIDs), and markedly increase the 
      left ventricular ejection fraction (LVEF, %) and left ventricular fractional 
      shortening (LVFS, %). Besides, carbachol could evidently lower the apoptosis 
      level of myocardial cells of septic rats (p<0.01), reduce the content of 
      inflammatory factors including tumor necrosis factor-alpha (TNF-alpha), interleukin-1ss 
      (IL-1ss) and IL-6 (p<0.01), notably decrease the expression of Caspase-3 in 
      myocardial tissues (p<0.01), remarkably increase the expression of Bcl-2/Bax 
      (p<0.01), and distinctly inhibit the expressions of phosphorylated (p-)PI3K, 
      p-AKT, Nod-like receptor protein 3 (NLRP3), and Caspase-1 (p<0.01). CONCLUSIONS: 
      Carbachol can reduce the release of inflammatory factors in myocardial cells, the 
      expression of apoptotic proteins and the apoptosis of myocardial cells, and 
      improve the cardiac function and survival rate of septic rats by inhibiting the 
      PI3K/AKT signaling pathway.
FAU - Zhou, L
AU  - Zhou L
AD  - Department of Critical Care Medicine, The First Affiliated Hospital of Shandong 
      First Medical University, Jinan, China. qfszhoulei@163.com.
FAU - Jiang, Z-M
AU  - Jiang ZM
FAU - Qiu, X-M
AU  - Qiu XM
FAU - Zhang, Y-K
AU  - Zhang YK
FAU - Zhang, F-X
AU  - Zhang FX
FAU - Wang, Y-X
AU  - Wang YX
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Italy
TA  - Eur Rev Med Pharmacol Sci
JT  - European review for medical and pharmacological sciences
JID - 9717360
RN  - 0 (Cholinergic Agonists)
RN  - 8Y164V895Y (Carbachol)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Carbachol/administration & dosage/*pharmacology
MH  - Cholinergic Agonists/administration & dosage/*pharmacology
MH  - Injections, Intraperitoneal
MH  - Male
MH  - Myocardial Reperfusion Injury/*drug therapy/metabolism/pathology
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Proto-Oncogene Proteins c-akt/*antagonists & inhibitors/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Sepsis/*drug therapy/metabolism/pathology
MH  - Signal Transduction/drug effects
EDAT- 2020/06/05 06:00
MHDA- 2021/03/26 06:00
CRDT- 2020/06/05 06:00
PHST- 2020/06/05 06:00 [entrez]
PHST- 2020/06/05 06:00 [pubmed]
PHST- 2021/03/26 06:00 [medline]
AID - 21356 [pii]
AID - 10.26355/eurrev_202005_21356 [doi]
PST - ppublish
SO  - Eur Rev Med Pharmacol Sci. 2020 May;24(10):5650-5658. doi: 
      10.26355/eurrev_202005_21356.