ABSTRACT
Objective To explore the protective effect of ginsenoside Rb1 on the myocardial ischemia / reperfusion (I / R) injury in rats in vitro. Methods Totally 60 adult male SD rats were randomly divided into 6 groups:sham group,I / R group,ginsenosde Rb1 pretreatment groups(at the doses of 1 μmol / L,5 μmol / L,10 μmol / L and 20 μmol / L,respectively), 10 in each group. The Langendorff perfusion system was used to establish I / R model. The Lab Chart electrophysiological system was used to monitor real-time heart function by monitoring heart rate (HR), left ventricular development pressure (LVDP) and left ventricular development pressure (± dp / dtmax). TTC staining method was used to measure myocardial infarct size. The Western blotting were used to assay Beclin 1, LC3, p62 and Lamp 2 expression, respectively. The immunohistochemistry were used to assay Beclin 1 expression. Results Ginsenoside Rbl of all the four different concent rations improved the decrease of LVDP and ± dp / dtmax arising from myocardial I / R injury. Meanwhile, ginsenoside Rbl significantly decreased the area of cardial infarction. Ginsenoside Rb1 (10 μmol / L) precondition group protected the heart most significantly (P<0. 05). The expression of Beclin 1 with I / R increased significantly in the cytoplasm of cardiomyocytes. Moreover, Beclin 1 expression decreased after addition pretreatment with ginsenoside Rb1 (10 μmol / L) (P < 0. 05). Compared with sham group, we found that the autophagic flux was impaired in I / R group which the expression of Beclin 1, LC3 and p62 increased significantly, as well as the expression of Lamp 2 decreased significantly. On the other hand, pretreatment with ginsenoside Rb1 (10 μmol / L) could reverse impaired autophagic flux (P < 0. 05). Conclusion Ginsenoside Rbl demonstrates pharmacological preconditioning effect and protects against myocardial I / R injury by improving damaged-autophagy flux, the dose of 10 μmol / L precondition protectes the heart most significantly.
ABSTRACT
Aim To investigate the effects of aralosdie C (SMC)isolated from aralosides on contractile func-tion and calcium transients in ischemia / reperfusion(I/R)-induced rat myocardial injury and the role of CaMK II. Methods The cardiomyocytes were divided into control group,I/ R group,I/ R + SMC group,KN-93+ I/ R + SMC group. The effect of SMC on the con-tractile function and calcium transient of I/ R cells was measured by cell shrinkage and ion concentration sim-ultaneous detection system. Results SMC(8 μmol· L - 1 )improved the contractile function of I/ R cardio-myocytes and the calcium transients,and SMC in-creased the rate of calcium transient and [Ca2 +]i up /down regulation significantly. While CaMK II was blocked by KN-93,the effect of SMC on contractile function and calcium transients was weakened. Con-clusions SMC can significantly improve the systolic function and calcium transients of cardiomyocytes in I/R rats,and the protective effect of SMC on cardiomyo-cytes may be related to CaMK II.
ABSTRACT
Aim To investigate whether the protection of rutaecarpine against myocardial ischemia / reperfusion (I/ R ) injury is mediated by Toll-like receptor 4 (TLR4)/ NF-κB pathway,and whether these effects are related to the release of calcitonin gene-related peptide(CGRP)in plasma. Methods Sprague-Daw-ley rats were subjected to 60 min of ligation of the left anterior descending coronary followed by 3h of reperfu-sion to induce I/ R injury. Rats were pretreated with rutaecarpine 10 min before the ligation,and some rats were pretreated with capsazepine 2 min before rutae-carpine administration. Myocardial infarct size,CGRP concentration in plasma and creatine kinase (CK)ac-tivity in serum were measured. The expression of TLR4 mRNA in myocardial tissue was determined by RT-PCR. The protein expression of TLR4 and NF-κB in myocardial tissue was analyzed by immunohistochemis-try. Results Rutaecarpine (100,300 μg · kg - 1 , iv)significantly reduced the infarct size and the serum CK activity concomitantly with the increase in plasma CGRP concentration (P < 0. 05). Importantly,the ex-pression of TLR4 (both mRNA and protein)and NF-κB (protein)was increased by myocardial I/ R injury, and dramatically inhibited by rutaecarpine pretreatment (P < 0. 05). All these effects of rutaecarpine were a-bolished by capsazepine (1. 5 mg·kg - 1 ,iv),a spe-cific antagonist for vanilloid receptor-1. Conclusion Rutaecarpine protects against myocardial I/ R injury by inhibiting TLR4 / NF-κB pathway,which is related to the increased release of CGRP.
ABSTRACT
Aim To verify the mechanisms underlying the protective effects of the 4-hydroxybenzaldehyde (4-HBd)on cerebral ischemia / reperfusion in vivo and in vitro. Methods The model of focal cerebral ischemi-a / reperfusion in rats was established by the suture-oc-clusion method. After reperfusion,neurological score and cerebral infarction rate were assessed. Meanwhile, after pretreatment with 4-HBd for 24 h,the primary cultured cortical neuron cells were exposed to oxygen glucose deprivation / reoxygenation (OGD/ Rep). The survival rate, MDA, SOD, NO, Bax, Bcl-2 and caspase-3 concentrations were assessed. Results Pre-treatment with 4-HBd significantly decreased neurologi-cal score (P < 0. 05)and cerebral infarction rate (P <0. 01)in the cerebrum after MCAO/ R injury. Further-more,4-HBd significantly increased cell survival rate (P < 0. 05),decreased MDA content (P < 0. 05),in-creased SOD activity (P < 0. 05),decreased NO levels (P < 0. 05),decreased caspase-3 (P < 0. 05),in-creased Bcl-2 (P < 0. 05)but decreased Bax (P <0. 05)levels and therefore increased Bcl-2 / Bax ratio in the cerebrum after OGD/ R injury. Conclusions 4-HBd has significant protective effect on MCAO/ R rats, and the mechanism may be related to decreasing NO levels,Bax,Bcl-2,caspase-3 and reducing neuronal apoptosis.