| Background and aimThe pathological phenomenon that hemoperfusion to the ischemic myocardium aggravating the tissue injury is myocardial ischemia reperfusion injury (IRI). IRI is frequently the severe complication during coronary artery bypass, percutaneous coronary intervention and thrombolytic therapy for myocardial infarction at present. The mechanisms of IRI involved Ca2+ overload, oxygen radicals, dysmetabolism, inflammation and etc. According to the present research data, it is indicated that the myocardial ischemia reperfusion could activate the nuclear factor-kappa B(NF-κB) and the activating factor may be the oxidative stress, Ca2+ overload, free radical, nitrogen monoxidum (NO), endotoxin and etc., resulted by IRI. NF-κB is obviously activated at the early stage of IRI. The activity of NF-κB increasing at the early stage of ischemia may relate to the regulation of early genes expression at the instant of IRI. It is indicated that the early activating of NF-κB resulted from ischemia is the acute molecular mechanism of regulating the gene expression of inflammation cell factor in heart. Recent studies show that Qidantongmai Tablet (QDTMT) plays an important part in inhibiting the Ca2+ inflow, degrading the amount of Ca2+ in the myocardial cells and mitochondria, lightening the calcium overload, increasing the activity of superoxide dismutase (SOD),glutathione peroxidase (GSH-Px) in myocardial mitochondria, and decreasing the content of malondialdehyde (MDA) in mitochondria. And thus QDTMT could effectively inhibit the destruction of oxygen free radical (OFR), reduce the size of myocardial infarction induced by ischemia and ischemia reperfusion, elevate the power of anti-oxidation and improve the function of the heart. To further investigate the mechanism that QDTMT protect the myocardial IRI, myocardial IRI model in rats was established with the coronary artery ligation, and the effects of QDTMT on ECG and the expression of NF-κB in rats with myocardial IRI were studied.Methods1. 48 healthy male SD rats were randomly divided into 6 groups, 8 rats per group: sham operation group, control group, QDTMT high dosage group (3.24 g/kg), QDTMT medium dosage group (1.08 g/kg), QDTMT low dosage group (0.36 g/kg), and Diltiazem Hydrochloride group (5 mg/kg). All rats were respectively administered with the same volume saline or drug liquid by gastrogavage once per day for 7 days, and myocardial IRI model was established through the coronary artery ligation method after the last gastrogavage was given for 40 minutes on the 7th day. The coronary arteries of rats in control group and drug groups were performed ligation 30 minutes and reperfusion 2 hours. The coronary arteries in sham operation group were threaded but not ligated. 2. When the experiment was over, tissues in the reperfused region was sampled immediately, some fixed for immunohistochemical staining, some preserved at -70℃for western blotting.3. Record the ECG during the operation. The protein levels of NF-κB were determined by immunohistochemical staining and western blotting.Results1. Compared with those of control group, the heart rate was stepped down and the drift of ST fragment of ECG was significantly lower in QDTMT high dosage group and Diltiazem Hydrochloride group.2. The expression of NF-κB was determined by immunohistochemical staining. Compared with those of sham operation group, the expression of NF-κB in the control group and QDTMT different dosage groups increased (P<0.01);Compared with those of control group, the expression of NF-κB in QDTMT different dosage groups and Diltiazem Hydrochloride group decreased (P<0.01); Compared with those of Diltiazem Hydrochloride group, the expression of NF-κB in QDTMT medium and low dosage groups increased.3. The protein levels of NF-κB were determined by western blotting. Compared with those of sham operation group, the protein levels of NF-κB increased in the rest groups(P<0.01). Compared with those of control group, the protein levels of NF-κB decreased in QDTMT different dosage groups and Diltiazem Hydrochloride group(P<0.01). Compared with those of QDTMT high dosage group, the protein levels of NF-κB increased in QDTMT medium and low dosage groups(P<0.01), while having no change in Diltiazem Hydrochloride group(P>0.05). Conclusions1. According to the observation result of the rate and the drift of ST fragment of ECG, it is demonstrated that Qidantongmai tablet provides remarkable protective effects in rat model of ischemia reperfusion.2. QDTMT has cardioprotective effect against IRI in rats possibly by inhibiting the expression of NF-κB. It may be one of the mechanisms that QDTMT lessens the myocardial IRI.3. QDTMT high dosage group almost has the same effect to inhibit the expression of NF-κB as Diltiazem Hydrochloride group.
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