塞来昔布对心肌梗死后心肌细胞凋亡的影响

 目的：研究选择性环氧化酶-2抑制剂塞来昔布(celecoxib,Cele)对心肌梗死后心肌细胞抗氧化损伤能力、Bcl-2、Bax蛋白表达及细胞凋亡的影响。方法：选择新西兰兔24只，随机分为3组（每组8只）：假手术组（sham组）、心肌梗死组（MI组）、塞来昔布组(Cele组，10 mg·kg^-1·d^-1,灌胃)。6周后取梗死灶边缘缺血心肌制作组织匀浆进行NO浓度(以NO^-₂/ NO^-₃间接表示)、结构型一氧化氮合酶(cNOS)和诱导型一氧化氮合酶(iNOS)活性及总抗氧化能力（T-AOC）测定，并做病理观察，免疫组化观察各组Bcl-2、Bax蛋白表达，TUNEL法比较其细胞凋亡程度。结果：MI组心肌间质水肿，较多心肌纤维化与炎性细胞浸润,心肌胞浆空泡样变，心肌肌原纤维间隙增宽，排列紊乱，可见局灶性肌丝溶解，肌浆网明显扩张。而Cele组病理改变较轻。Cele组心肌组织匀浆中NO^-₂/ NO^-₃浓度、iNOS活性低于MI组，cNOS活性及T-AOC高于MI组(P<0.05)； Cele组Bcl-2表达阳性率高于MI组而bax表达率低于MI组（P<0.01）；细胞凋亡程度低于MI组（P<0.01）。结论：塞来昔布可增强心肌梗死后心肌细胞抗氧化损伤能力并降低细胞凋亡率。

Effects of celecoxib on cardiac myocyte apoptosis after myocardial infarction

AIM: To investigate the effects of celecoxib, a selective cyclooxygenase-2 inhibitor, on antioxidative capability and apoptosis of cardiac myocytes after myocardial infarction. METHODS: 24 New Zealand rabbits were divided into three groups randomly (8 in each group): sham-operated group (sham group), myocardial infarction group (MI group), celecoxib group (Cele group, 10 mg kg^-1·d^-1, qd, with the drugs gastric gavage for six weeks). The NO concentration, total antioxidative capability (T-AOC), the activity of constitutive nitric oxide synthase (cNOS) and inducible NOS (iNOS) in cardiac tissue homogenate, adjacent to the infracted area, were detected. The pathological changes were observed by light microscope and electron microscopy. The expressions of Bcl-2 and Bax protein in myocytes were observed using immunohistochemistry, and the degree of apoptosis were examined by TUNEL. RESULTS: Cardiac tissue in MI group presented interstitial edema, fibroplastic proliferation, inflammatory cellular infiltration, and vacuolar degeneration in cardiac myocytes. The results of electron microscopy showed that myocytes presented more changes caused by ischemic injury: widened interspace of myofibril, disordered myofibrillae, focal lysis of myofilament, ectasia of sarcoplasmic reticulum. In Cele group, the pathological changes were light, the NO^-₂/ NO^-₃ concentration, the activity of iNOS were lower (P<0.05), while the activity of cNOS and T-AOC were higher (P<0.05) than those in MI group. The expression rate of Bcl-2 protein in Cele group was higher than that in MI group, while the Bax was lower (P<0.01). The number of apoptotic myocytes was lower than that in MI group (P<0.01). CONCLUSION: Celecoxib decreases the number of apoptotic cardiomyocytes and increases the antioxidative capability after myocardial infarction.