1.Effects of Nicardipine on Apoptosis in Ischemia Reperfusion Myocardium of Rabbits
Lu HAN ; Jizhuo ZHANG ; Xinghua CHEN
Journal of China Medical University 2016;45(8):746-749
Objective To investigate the effects of nicardipine on apoptosis in ischemia?reperfusion myocardium of rabbits. Methods Forty New Zealand rabbit were randomly divided into 4 groups:control group(group A),ischemia group(group B),ischemia?reperfusion group(group C),ni?cardipine treatment group(group D). Ischemia?reperfusion model was established by left circumflex branch coronary artery ligation for 40 min,fol?lowed by 120 min reperfusion. Apoptotic cardiomyocyte was detected using the analysis for the exposure of phosphatidyl?serine ( Annexin V)meth?od. Results Myocardial cell damage was lower in D group than that in group B and group C from pathology(P<0.01). The myocardial cell apopto?sis in group D is less than that of group B and group C(P<0.01),but higher than that of group A(P<0.05). Myocardial cell necrosis is lower than group B and group C(P<0.01),and no difference was found comparing with group A(P>0.05). Conclusion Nicardipine horizon can reduce the myocardial cell apoptosis in rabbits with myocardial ischemic reperfusion injury.
2.Effects and mechanism of astilbin on myocardial ischemia-reperfusion injury in rats
Xinghua CHEN ; Lu HAN ; Ming GONG ; Jizhuo ZHANG
China Pharmacy 2023;34(10):1193-1198
OBJECTIVE To investigate the effects of astilbin (AST) on myocardial ischemia-reperfusion injury (MIRI) in rats and its potential mechanism. METHODS SD male rats were randomly divided into sham operation group, model group, positive control group (Compound Salvia miltiorrhiza tablets, 240 mg/kg), AST low-dose and high-dose groups (30, 90 mg/kg), and high- dose of AST+hypoxia-inducible factor-1α(HIF-1α) inhibitor group (AST 90 mg/kg+2ME2 15 mg/kg), with 25 rats in each group. Except for sham operation group, MIRI model was induced in other groups, and then given relevant drug or normal saline intragastrically or intraperitoneally, for consecutive 28 d. Serum contents of cardiac troponin I (cTnI) and creatine kinase isoenzyme (CK-MB) were detected; volume ratio of myocardial infarction was measured; the pathological changes of myocardium, the apoptotic rate of myocardial cells and ultrastructure of mitochondria in myocardial tissue were all observed. The contents of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6) and malondialdehyde (MDA), the activity of superoxide dismutase (SOD), the expressions of HIF-1α, adenovirus E1B interacting protein 3 (BNIP3) and myosin-like Bcl-2 interacting protein (Beclin1) were determined in myocardium. The ratio of microtubule-associated protein light chain 3 (LC3) Ⅱ to Ⅰ (LC3 Ⅱ/Ⅰ) in rat myocardium was calculated. RESULTS Compared with model group, no obvious swelling was found in the myocardial tissue of rats in positive control group, AST low-dose and high-dose groups, and the myocardial fibers were arranged regularly; the volume ratio of myocardial infarction, the contents of cTnI, CK-MB, TNF-α, IL-6 and MDA, the apoptotic rate were decreased significantly (P<0.05), while SOD activity, protein expressions of HIF-1α, BNIP3 and Beclin1, LC3Ⅱ/Ⅰ were increased significantly (P<0.05). HIF-1α inhibitor could significantly weaken the improvement effect of AST on the above indicators in MIRI model rats (P<0.05). CONCLUSIONS AST enhances mitochondrial autophagy by activating HIF-1α/BNIP3 signaling pathway, thereby reducing MIRI in rats.
3.Effects of aspirin on myocardial injury in rats with myocardial ischemia/reperfusion by regulating miR-340-5p/HMGB1/TLR4 pathway
Xinghua CHEN ; Jizhuo ZHANG ; Lu HAN
China Pharmacy 2022;33(20):2508-2513
OBJECTIVE To investigate the effects of a spirin (Asp) on myocardia l ischemia/reperfusion (I/R) injury by regulating microRNA -340-5p (miR-340-5p)/high mobility group box 1 (HMGB1)/Toll-like receptor 4 (TLR4) pathway. METHODS Male SD rats were divided into sham operation (Sham)group(thoracotomy without ligation ),I/R group (I/R injury model was constructed ),and Asp pretreatment (I/R+Asp)group(7 d of Asp pretreatment+modeling ),I/R+Asp+in-miR-340-5p group [Asp pretreatment 7 d+transfection with miR -340-5p inhibitor 48 h before modeling+modeling ] and I/R+Asp+HMGB 1 group (7 d of Asp pretreatment+transfection with overexpression of HMGB 1 48 h before modeling+modeling ),with 20 rats in each group. The levels of myocardial injury indexes [lactate dehydrogenase ,creatine kinase isoenzyme -MB,cardiac troponin Ⅰ], inflammation and oxidative stress indexes [myeloperoxidase,superoxide dismutase ,glutathione peroxidase ,malondialdehyde] were detected in each group ,and the pathological changes of myocardial tissue were observed . The myocardial infarction area ,cell apoptosis and the expression of miR -540-5p,HMGB1 and TLR 4 in myocardial tissue were detected . Cardiomyocyte H 9C2 of rats was used as the object to investigate the targeting relationship between miR -340-5p and HMGB 1. RESULTS Asp pretreatment could significantly inhibit the increase of serum myocardial injury indexes in I/R model rats ,reduce inflammation and inhibit oxidative stress ,reduce myocardial infarct size and apoptosis ,and significantly up -regulated the expression of miR -340-5p and down-regulated the expression of HMGB 1 and TLR 4 proteins(P<0.05);inhibition of miR -340-5p or overexpression of HMGB 1 could reverse the above protective effects of Asp (P<0.05). miR-340-5p could target and negatively regulate HMGB 1 expression (P<0.05). CONCLUSIONS Asp can reduce inflammation and oxidative stress by regulating the miR -340-5p/HMGB1/TLR4 pathway,reduce apoptosis i n myocardial tissue ,and play a protective role against myocard ial I/R injury .