格列齐特对2型糖尿病大鼠心肌缺血预适应保护作用的影响

目的 探讨格列齐特对2型糖尿病大鼠离体心脏缺血预适应保护作用的影响。方法 将造模成功的2型糖尿病大鼠随机分为糖尿病缺血预处理组、糖尿病再灌注损伤组、糖尿病缺血预处理+格列齐特组、糖尿病再灌注损伤+格列齐特组。将对照组大鼠随机分为缺血预处理组、再灌注损伤组。分别于平衡灌注后、缺血再灌注开始及再灌注60 min末3个时间点分别收集冠脉流出液,测定乳酸脱氢酶（LDH）、肌酸激酶（CK）、肌酸激酶同工酶（CK-MB）的释放量;在再灌注末,取左心室游离壁心肌组织,进行荧光定量PCR检测心肌ATP敏感性钾离子（KATP）通道组成亚基Kir6.2和SUR2A mRNA的表达;免疫组织化学技术检测其蛋白的表达水平。结果 对于糖尿病非药物治疗大鼠,糖尿病缺血预处理组与糖尿病再灌注损伤组比较,冠脉流出液中LDH、CK、CK-MB无明显差异;Kir6.2和SUR2A mRNA及蛋白表达也均无明显差异。而与糖尿病缺血预处理组、糖尿病再灌注损伤+格列齐特组比较,糖尿病缺血预处理+格列齐特组均降低了糖尿病大鼠心肌缺血预处理后缺血再灌注损伤冠脉流出液中LDH、CK、CK-MB释放量（P<0.05）;也使Kir6.2 mRNA及蛋白表达明显增加（P<0.05）;但SUR2A mRNA表达差异无统计学意义。与糖尿病再灌注损伤+格列齐特组比较,糖尿病缺血预处理+格列齐特组SUR2A蛋白表达水平也增加明显（P<0.05）。结论 格列齐特对心肌缺血预处理的保护作用无不利影响,反而能改善2型糖尿病大鼠心肌缺血预适应的保护作用。     

The myocardial infarct size-limiting and antiarrhythmic effects of acyl-CoA:cholesterol acyltransferase inhibitor VULM 1457 protect the hearts of diabetic-hypercholesterolaemic rats against ischaemia/reperfusion injury both in vitro and in vivo

The study was designed to characterise the influence of a novel acyl-CoA:cholesterol acyltransferase inhibitor, VULM 1457, on the severity of myocardial ischaemia-reperfusion injury in a model of diabetes mellitus and hypercholesterolaemia induced by co-administration of streptozotocin and a high fat-cholesterol diet. We used Langendorff-perfused rat hearts to measure the size of myocardial infarction after 30 min of regional ischaemia, followed by a 2-h reperfusion period, and open-chest rats were exposed to 6 min of ischaemia and 10 min of reperfusion to analyse ventricular arrhythmias. In addition to the high fat-cholesterol diet, VULM 1457 was administered to the diabetic-hypercholesterolaemic rats for 5 days. Decreased plasma and liver cholesterol levels and a significantly reduced occurrence of ventricular fibrillation (29% vs. 100%, P<0.01), determined via the mean number and duration of episodes (0.6+/-0.4 and 2.1+/-1.4 s vs. 2.8+/-0.8 and 53.5+/-14.4 s in diabetic-hypercholesterolaemic rats, both P<0.01), were observed in these animals. Lethal ventricular fibrillation was suppressed, and arrhythmia severity was also significantly decreased in these animals as compared to the non-treated animals (2.9+/-0.6 vs. 4.9+/-0.2; P<0.05). A smaller infarct size, normalised to the size of area at risk, was observed in the treated diabetic-hypercholesterolaemic group as compared to the non-treated group (16.3+/-1.9% vs. 37.3+/-3.1%; P<0.01). Aside from remarkable hypolipidaemic activity, VULM 1457 improved the overall myocardial ischaemia-reperfusion injury outcomes in the diabetic-hypercholesterolaemic rats by suppressing arrhythmogenesis as well as by reducing myocardial necrosis.     

Efficacy of ischaemic preconditioning in the eNOS overexpressed working mouse heart model

We recently demonstrated that exogenous nitric oxide (NO) acts as a trigger for preconditioning in the isolated rat heart model. There is however little data concerning the effects of elevated cardiac endothelial nitric oxide synthase (eNOS) expression on myocardial tolerance to ischaemia. Similarly, the effects of gender and eNOS overexpression on ischaemic preconditioning is unknown. We hypothesized that: 1) eNOS overexpression increases myocardial tolerance to ischaemia, and, 2) eNOS overexpressed hearts cannot be preconditioned, since the hearts are already maximally protected. Male and female wild-type and transgenic mice that overexpress eNOS exclusively in cardiac myocytes were perfused in the working heart mode with a modified Krebs-Henseleit buffer at a pre-load of 12.5 mm Hg and afterload of 50 mm Hg. Cardiac output, coronary flow, peak aortic systolic pressure and total work were determined before hearts were preconditioned by 4x5 min cycles of ischaemia/reperfusion, and then subjected to 20 min total global ischaemia, followed by reperfusion. Reperfusion function and myocardial infarct size were used as endpoints. Pre-ischaemic mechanical function (rate pressure product and cardiac output) was similar for wild-type and transgenic mice of both sexes. The eNOS overexpressed hearts had smaller infarcts than the hearts from their wild-type littermates (26.9+/-1.4% vs. 37.0+/-2.1% for controls, P<0.05). Preconditioning the eNOS overexpressed hearts resulted in infarct sizes comparable with control non-preconditioned hearts (27.5+/-2.0% vs. 26.9+/-1.4% for controls). Myocardial cGMP levels were elevated during sustained ischaemia in the transgenic hearts when compared with wild-type hearts (22.43+/-1.63 pmol/g ww vs 16.54+/-1.48 pmol/g ww, P<0.05). Preconditioning also elevated myocardial cGMP levels during sustained ischaemia in the wild-type hearts (26.77+/-2.81 pmol/g ww, P<0.05). We conclude that: 1) basal mechanical function is similar for both wild-type and transgenic mice of both sexes, 2) reperfusion function and infarct size was also similar for both sexes under both control conditions and after preconditioning, 3) the transgenic mice are more tolerant of ischaemia as reflected by their smaller myocardial infarcts, and, 4) the eNOS overexpressed mouse heart cannot be preconditioned regardless of whether mechanical function or infarct size is used as an end-point. These hearts may be maximally protected against ischaemia/reperfusion injury by their elevated endogenous NO levels.     

Effects of zoledronate in the repair of chronically infarcted rat myocardium

Zoledronate (Zol), one of the class of bisphophonate drugs, is commonly used to treat postmenopausal osteoporosis. Treatment of liposomal bisphosphonates has been shown to worsen myocardial infarct repair in an experimental model. The purpose of this study was to investigate the effect of Zol in the repair of chronically infarcted myocardium without liposomal encapsulation to mimic the clinical setting. Zol (20 μg/kg, a dose known to treat experimental osteoporosis in rats, n = 15) was administered subcutaneously to female Sprague-Dawley rats 1 day before coronary artery ligation. Rats receiving phosphate-buffered saline (n = 12) were used as controls. Left ventricular function, infarct size, and remodeling were studied at 4 weeks postinfarction. Zol pretreatment did not affect left ventricular ejection fraction in hearts with myocardial infarction (49.5 ± 1.4% in Zol; 50.6 ± 2.1% in phosphate-buffered saline). Infarct size was similar in Zol versus untreated hearts (34.2% ± 2.9% in Zol; 33.4% ± 2.9% in phosphate-buffered saline). Left ventricular cavity volume and circumference, infarct thickness, and expansion index were comparable between the groups. To investigate a potential effect of Zol on tissue macrophage infiltration after myocardial infarction, heart specimens were harvested 48 hours postinfarction and sections were immunostained with CD68 antibody, a macrophage-specific marker. Results of macrophage immunostaining revealed that the level of tissue macrophage infiltration was similar between groups. In conclusion, administration of Zol before myocardial infarction had no adverse effects on cardiac contractile function, infarct size, or remodeling. These results suggest that treatment of Zol given before the onset of myocardial infarction does not cause worsening of infarct repair.     

Effects of the angiotensin II subtype 1 receptor antagonist losartan on functional recovery of isolated rat hearts undergoing global myocardial ischemia-reperfusion

STUDY OBJECTIVE: To investigate the effects of the angiotensin II subtype 1 receptor (AT1R) antagonist losartan on functional recovery of isolated rat hearts undergoing global myocardial ischemia-reperfusion compared with myocardial protective effects of ischemic preconditioning. DESIGN: Ex vivo experiment using isolated perfused rat heart. SETTING: Academic laboratory. INTERVENTION: Hearts from Sprague-Dawley rats were perfused with oxygenated Krebs-Henseleit buffer and randomized to one of four groups: time control, vehicle, ischemic preconditioning, or losartan. MEASUREMENTS AND MAIN RESULTS: After randomization, hearts underwent 30 minutes of global ischemia followed by 30 minutes of reperfusion. Changes in end-diastolic pressure (EDP), left ventricular developed pressure (LVDP), and infarct size were examined between treatment groups by two-way analysis of variance with repeated measures. Cardiac angiotensin II receptor (ATR) density and infarct size were measured in control hearts and in a subgroup of hearts exposed to ischemia-reperfusion injury. Total ATR density and percentage of myocardial AT1R were increased in hearts exposed to ischemia-reperfusion. Myocardial ischemia-reperfusion injury resulted in a 56% reduction in LVDP from baseline in hearts randomized to vehicle. However, it declined by only 22% and 28% in hearts randomized to ischemic preconditioning and losartan, respectively. Compared with vehicle, both ischemic preconditioning and losartan decreased EDP (ischemic preconditioning 39 +/- 3 mm Hg, losartan 54 +/- 5 mm Hg, vs vehicle 78 +/- 8 mm Hg), and reduced infarct size (ischemic preconditioning 9%, losartan 12%, vs vehicle 36%). CONCLUSION: Treatment of isolated rat hearts with losartan before ischemia-reperfusion injury resulted in significant cardioprotection similar to that observed with ischemic preconditioning.     

Effects of thalidomide on isoprenaline-induced acute myocardial injury: a haemodynamic, histopathological and ultrastructural study

In the present study, we investigated the cardioprotective effects of thalidomide in a rat model of acute myocardial injury, induced by subcutaneous injection of isoprenaline hemisulphate (85 mg/kg per day for 2 days). Thalidomide (75/150/300 mg/kg) or vehicle (dimethylsulphoxide) or saline (0.9% NaCl) was administered orally for 14 days and isoprenaline injection on the 12th and 13th days. Cardiovascular responses (arterial and left ventricular haemodynamic parameters and heart rate) were obtained in anaesthetized rats on the 14th day. Histopathological and electronmicroscopical analysis of myocardial injury was done. The results showed that thalidomide 300 mg/kg per day orally caused significant improvement in isoprenaline-induced reduction of cardiac function with increases in maximum rate of pressure development (+LVdP/dt, P < 0.001) and maximum rate of pressure decline (-LVdP/dt, P < 0.001) and decreases in left ventricular end-diastolic pressure (P < 0.01), systolic arterial pressure (P < 0.001), diastolic arterial pressure (P < 0.001), mean arterial pressure (P < 0.001) and heart rate (P < 0.001). The myocardial injury caused by isoprenaline was significantly reduced by thalidomide treatment as judged by the reduction of myocardial necrosis, ultrastructural changes such as mitochondria and myofibril damage, 300 mg/kg being the most effective dose. In conclusion, oral administration of thalidomide is able to ameliorate isoprenaline-induced myocardial injury and impaired myocardial function in spite of decreases in systolic arterial pressure, diastolic arterial pressure and mean arterial pressure, which may be due to its depressant effect on the sino-atrial node and sedative action.     

Captopril modifies the response of infarcted rat hearts to isoprenaline stimulation.

In this study the effect of the angiotensin converting enzyme (ACE) inhibitor captopril on beta-receptor responsiveness was investigated in failing rat hearts after experimental myocardial infarction. Infarcted rats were treated for 8 weeks with either captopril added to the drinking water (100 mg/kg/day; n = 5) or drinking water alone (n = 7). Treatment was started 2-3 days before myocardial infarction. A third group of untreated rats without myocardial infarction served as control (n = 6). At the end of the treatment period the hearts were perfused as described by Langendorff, and a cumulative dose-response curve of isoprenaline was obtained in each heart. In comparison with noninfarcted hearts, the response of heart rate and peak pressure rate (dP/dt) to isoprenaline stimulation was significantly depressed in hearts of infarcted rats. Chronic treatment with captopril significantly attenuated the reduced responsiveness to isoprenaline stimulation. This improved responsiveness in captopril-treated rat hearts might be due to prevention of "down-regulation" of myocardial beta-adrenoceptors. Other factors should also be considered, such as prevention of structural alterations in the noninfarcted myocardium, e.g., myocardial hypertrophy and fibrosis. Differences in infarct size did not play an important role, since infarct size was comparable in both groups of infarcted rats. This partial preservation of beta-adrenergic responsiveness was accompanied by a significant reduction in right ventricular weight and lung weight, suggesting that captopril also improved the signs of heart failure. Therefore, the results of this study indicate that early ACE inhibition in myocardial infarction may be useful in preventing deterioration of cardiac function.     

Mechanisms of cardioprotective effect of Withania somnifera in experimentally induced myocardial infarction

The present study was designed to evaluate the cardioprotective potential of hydro-alcoholic extract of Withania somnifera on the basis of haemodynamic, histopathological and biochemical parameters in the isoprenaline-(isoproterenol) induced myocardial necrosis in rats and to compare with Vitamin E, a known cardioprotective antioxidant. Wistar albino male rats (150-200 g) were divided into six main groups: sham, isoprenaline control, Withania somnifera/Vitamin E control and Withania somnifera/Vitamin E treatment groups. Withania somnifera was administered at doses 25, 50 and 100 mg/kg and Vitamin E at a dose of 100 mg/kg, orally for 4 weeks. On days 29 and 30, the rats in the isoprenaline control and Withania somnifera/Vitamin E treatment groups were given isoprenaline (85 mg/kg), subcutaneously at an interval of 24 hr. On day 31, haemodynamic parameters were recorded and the hearts were subsequently removed and processed for histopathological and biochemical studies. A significant decrease in glutathione (P<0.05), activities of superoxide dismutase, catalase, creatinine phosphokinase and lactate dehydrogenase (P<0.01) as well as increase in lipid peroxidation marker malonyldialdehyde level (P<0.01) was observed in the hearts of isoproterenol control group rats as compared to sham control. However, we have not observed any significant changes in activity of glutathione peroxidase and protein levels. Left ventricular dysfunction was seen as a decrease in heart rate, left ventricular rate of peak positive and negative pressure change and elevated left ventricular end-diastolic pressure in the control group was recorded. On histopathological examination, myocardial damage was further confirmed. Our data show that Withania somnifera (25, 50 and 100 mg/kg) exerts a strong cardioprotective effect in the experimental model of isoprenaline-induced myonecrosis in rats. Augmentation of endogenous antioxidants, maintenance of the myocardial antioxidant status and significant restoration of most of the altered haemodynamic parameters may contribute to its cardioprotective effect. Among the different doses studied, Withania somnifera at 50 mg/kg dose produced maximum cardioprotective effect.     

蝙蝠葛酚性碱对心肌缺血及缺血再灌注损伤的保护作用

目的研究蝙蝠葛酚性碱(PAMD)对心肌缺血及缺血再灌注损伤的作用。方法用大鼠皮下注射异丙肾上腺素85 mg.kg-1造成心肌缺血模型,于造模前30 min灌胃给予生理盐水、PAMD(7.5,15或30 mg.kg-1)、地尔硫10 mg.kg-1或地奥心血康150 mg.kg-1,测定心肌缺血后乳酸脱氢酶(LDH)、肌酸激酶(CK)、超氧化物歧化酶(SOD)和丙二醛(MDA)含量及病理学改变。离体大鼠心脏缺血30 min再灌注40 min,分别给予PAMD(1,10或100 mg.L-1)或地奥心血康100 mg.kg-1,测定心肌缺血再灌注后左室收缩压(LVSP)、左室舒张末压(LVEDP)和左室压最大变化速率(±dp/dtmax)、冠脉流量,测定心肌SOD活性和MDA含量。结果 PAMD显著降低缺血所致的LDH、CK和MDA升高,提高SOD活性,减轻心肌病理损伤。PAMD促进缺血再灌注末LVSP、LVEDP和±dp/dtmax等恢复,增加冠脉流量和SOD活性并降低MDA含量。结论 PAMD对心肌缺血及缺血再灌注损伤有保护作用,其机制可能与其抗氧化及改善心肌代谢有关。     

Effect of Policosanol on Isoprenaline-induced Myocardial Necrosis in Rats

Abstract— Policosanol is a mixture of higher aliphatic primary alcohols isolated from sugar cane (Saccharum officinarum L.) and octacosanol represents its main component. This study was conducted to examine the effects of policosanol on myocardial necrosis induced by subcutaneous injection of isoprenaline in rats. A significant reduction (P < 0·01) of infarct size, polymorphonuclear cells and mast cells was observed in animals treated with policosanol at 5 or 25 mg kg^?1, while animals receiving only acetysalicylic acid pretreatment showed a significant decrease in the infarct area (P < 0·05). No significant differences in polymorphonuclear and mast cells were obtained when compared with positive control data. It is concluded that policosanol delays the evolution of infarction, showing a protective effect on the myocardial necrosis induced by isoprenaline in this experimental model.     

Effects of endothelin ETA receptor blocker LU 135252 on cardiac remodeling and survival in a hypertensive rat model of chronic heart failure

AIM: To investigate whether the endothelin ETA receptor blocker provides similar benefit on cardiac remodeling and survival in a hypertensive rat model of chronic heart failure (CHF). METHODS: Male stroke-prone spontaneously hypertensive (SHR-SP) rats were subjected to permanent ligation of the left coronary artery and were treated for 6 weeks with the endothelin ETA receptor blocker LU 135252 (30 mg.kg(-1).d(-1)) starting 24 h after ligation or untreatment. Sham-operated rats served as normal controls. The mean arterial blood pressure (MAP), heart rate (HR), left ventricular end-diastolic pressure (LVEDP), left ventricular contractility (LV dp/dt(max)), left ventricular inner diameter (LVD) and circumference (LVC), septal thickness, left ventricular interstitial collagen content (ICC) and heart weight (HW) were measured at the end of the treatment. RESULTS: Compared with the untreated group, LU 135252 tended to increase HW (1.43 +/-0.03 vs 1.38 +/-0.04 g; P> 0.05), increased LVD (7.65+/-0.24 mm vs 6.58+/-0.14 mm; P<0.05), markedly increased LVC (30.11+/-0.83 mm vs 24.82+/-0.85 mm; P< 0.01) and reduced left ventricular ICC (3.79%+/-0.09% vs 6.71%+/-0.11%; P< 0.01), slightly lowered MAP (132+/-6 mmHg vs 142+/-4 mmHg; P>0.05), reduced LVEDP (14 4 mmHg vs 27+/-4 mmHg; P<0.05) and improved LV dp/dtmax (4230+/-450 mmHg/s vs 1950+/-400 mmHg/s; P<0.05); survival was not prolonged significantly (13% vs 11%; P=NS). CONCLUSION: In this hypertensive rat model of CHF, chronic endothelin ETA receptor blockade with LU 135252 improves cardiac hemodynamics, however, it does not affect long-term survival and worsens cardiac remodeling. Thus, endothelin ETA receptor antagonists are unlikely to have an important role in the management of patients with CHF.     

Janus激酶-信号转导子与转录激活子信号通路在硫化氢后处理离体缺血再灌注大鼠心肌中的作用

目的 探讨Janus激酶-信号转导子与转录激活子(JAK2/STAT3)信号通路在硫化氢后处理(H2S)减轻离体大鼠心脏缺血/再灌注(I/R)损伤的作用.方法 应用Langendorff离体心脏灌流装置、通过停灌30 min/复灌60 min的方法建立SD大鼠I/R模型.按照处理及再灌注成分分为持续灌注对照组,I/R组...     

Cytochrome P450 2J3/epoxyeicosatrienoic acids mediate the cardioprotection induced by ischaemic post-conditioning, but not preconditioning, in the rat

1. Cytochrome P450 (CYP) epoxygenases and their arachidonic acid metabolites play a protective role against ischaemia-reperfusion injury. In the present study, we investigated whether endogenous CYP2J3/epoxyeicosatrienoic acid (EET) mediates the cardioprotective effects of ischaemic preconditioning (IPC) and ischaemic post-conditioning (IPost). 2. Male Wistar rats were subjected to two cycles of IPC, consisting of 5 min ischaemia and 5 min reperfusion, followed by 45 min occlusion and 2 h reperfusion; IPost consisted of three cycles of 30 s reperfusion and 30 s re-occlusion at the onset of reperfusion. The selective CYP epoxygenase inhibitor N-methylsulphonyl-6-(2-propargyloxyphenyl)hexanamide (MS-PPOH; 3 mg/kg) was administered 10 min before ischaemia or during ischaemia 10 min before reperfusion started. Cardiac function was measured continuously with a angiocatheter connected to a fluid-filled pressure transducer and myocardial infarct size was assessed by triphenyl tetrazolium chloride staining at the end of the experiment. 3. Subjecting rats to IPC and IPost similarly improved cardiac function and reduced myocardial infarct size. Interestingly, IPost, but not IPC, significantly increased CYP2J3 mRNA (1.75 ± 0.22 vs 1.0; P < 0.05) and protein (1.62 ± 0.22 vs 1.0; P < 0.05), as well as 11,12-EET synthesis compared to I/R (6.2 ± 0.2 vs 2.9 ± 0.2 ng/mg wet weight, respectively; P < 0.01). Administration of MS-PPOH before ischaemia significantly decreased 11,12-EET synthesis in both IPC and IPost compared with I/R rats (2.1 ± 0.2, 3.2 ± 0.3 and 2.9 ± 0.2 ng/mg wet weight, respectively; P < 0.01), but decreased the cardioprotective effects, as evidenced by cardiac function and myocardial infarct size, of IPost only. 4. These data indicate that endogenous activation of CYP2J3/EET may be an essential trigger leading to the protective effects of IPost, but not IPC, in the rat heart.     

瑞舒伐他汀后处理通过抑制高迁移率族蛋白表达减轻心肌缺血再灌注损伤的研究

目的：研究瑞舒伐他汀（RS）后处理是否可以通过抑制高迁移率族蛋白（HMGB1）的表达减轻心肌缺血再灌注损伤（I／R）。方法使用 SD 大鼠缺血再灌注模型,缺血30 min,再灌4 h。将大鼠随机分为假手术组（n＝10）、缺血再灌注组（n＝15）和 RS 后处理组（n＝15）三组,检测血清中乳酸脱氢酶（LDH）水平和肌酸激酶（CK）活性、心肌组织中超氧化物歧化酶（SOD）活性和丙二醛（MDA）水平及心肌梗死面积和心肌中 HMGB1的表达水平。结果 RS 后处理能明显减少梗死面积（P ＜0．05）及 LDH、CK 活性（P 均＜0．05）;明显抑制 MDA 的升高和 SOD 的活性（P 均＜0．05）;明显抑制 HMGB1的表达（P ＜0．05）。结论 RS 后处理对心肌 I／R 的保护作用与抑制 HMGB1的表达有关。     

格列齐特对大鼠局灶性脑缺血再灌注损伤的保护作用及机制研究

目的: 以大脑中动脉栓塞(MCAO)/再灌注模型为研究对象,探讨格列齐特对缺血性脑卒中的保护作用及机制。方法: 雄性Wistar大鼠采用线栓法进行2h左侧MCAO/再灌注,对不同再灌注时间点的梗死核心区样本检测mRNA水平及SUR1蛋白表达水平;不同剂量格列齐特静脉注射到右颈内静脉后灌注12h,采用TUNEL法检测凋亡细胞数量、采用Bederson试验评价神经功能缺损、采用TTC染色法观察脑梗死体积。结果: SUR1mRNA和蛋白水平在MCAO/再灌注组织中显著上调,在缺血后8~12h达到最大水平。格列齐特可减少TUNEL阳性细胞数量,减轻神经功能损伤和脑梗死体积。结论: 研究表明SUR1信号通路可能与MACO/再灌注损伤及梗死相关,静脉注射格列齐特可通过抑制SUR1的表达减轻梗死程度,减少MACO/再灌注造成的梗死面积及脑细胞凋亡程度。     

外源性硫化氢后处理对大鼠心肌缺血/再灌注损伤线粒体通透性转换孔的影响

目的探讨硫化氢(hydrogen sulfide,H2S)供体——硫氢化钠(sodium hydrosulfide,NaHS)后处理对大鼠离体心脏缺血/再灌注损伤时线粒体通透性转换孔(mitochondrial per-meability transition pore,MPTP)的影响。方法 60只♂SD大鼠,随机分为5组(n=12):空白组(Control)、缺血/再灌注组(I/R)、NaHS后处理组(N)、苍术苷组(A)、NaHS后处理+苍术苷组(N+A)。采用Langendorff离体心脏灌注模型。Con组持续灌注120 min,其余各组均平衡灌注30 min,全心缺血30 min,复灌60 min。其中,N组复灌即刻给予含有NaHS的K-H液后处理,A组复灌初给予含有苍术苷(MPTP特异性开放剂)的K-H液灌注10 min,N+A组在NaHS处理后,给予苍术苷处理10 min。记录各组平衡末、复灌10、30、60 min心功能指标。复灌末各组取心脏,TUNEL法观察心肌细胞凋亡情况,氯化三苯基四氮唑(TTC)染色法分析心肌梗死面积。结果与I/R组相比,NaHS后处理组可改善缺血/再灌注损伤心功能的各项指标(P<0.05),减少心肌梗死面积(P<0.05),降低凋亡指数(P<0.05)。苍术苷则可以取消NaHS的作用。结论外源性H2S后处理能减轻大鼠心肌缺血/再灌注损伤,该作用与其抑制MPTP开放有关。     

地塞米松预处理对大鼠心肌HSP72的表达和I/R心肌梗塞面积的影响

目的 探讨地塞米松预处理对SD大鼠心肌热休克蛋白72(HSP72)的表达和缺血-再灌注(I/R)心肌梗塞面积的影响.方法 SD大鼠随机分成地塞米松、安慰剂组,分别给予地塞米松和生理盐水预处理.24小时后构建Langendorff离体心脏I/R动物模型,缺血30分钟后再灌注60分钟,Western blot法和免疫组化法观察心肌HSP72表达变化;TTC染色,影像法测定心肌梗塞面积.结果 地塞米松预处理诱导大鼠心肌HSP72的表达较安慰剂组显著增加(P＜0.05);经地塞米松预处理后可缩小心肌梗塞面积(P＜0.01).结论 地塞米松作为新型HSP72诱导剂,上调HSP72表达,可有效地缩小大鼠I/R心肌的梗塞面积.     

The angiotensin II AT1-receptor antagonist candesartan improves functional recovery and reduces the no-reflow area in reperfused ischemic rat hearts.

It is not yet clear if cardiac angiotensin II is involved in the pathophysiology of myocardial ischemia/ reperfusion injury. The aim of this study was to investigate the effect of the angiotensin II AT1-receptor antagonist candesartan on myocardial functional recovery in isolated rat hearts subjected to ischemia and reperfusion. Three groups of hearts perfused in the Langendorff mode with Krebs-Henseleit buffer under constant pressure received either vehicle (n = 7), candesartan, 1 nM (n = 6), or 100 nM (n = 7) at the start of 30 min of global ischemia. The recovery of the double product was significantly higher in the candesartan, 100 nM, group (75+/-9.2%) than in the vehicle group (40+/-5.1%; p < 0.05). At the end of 30 min of reperfusion, left ventricular end diastolic pressure was lower in rats given candesartan, 100 nM, than in rats given vehicle (10+/-4.3 vs. 38+/-4.8 mm Hg; p < 0.05). After ischemia and reperfusion, there was a large no-reflow area in the vehicle group (28+/-3.1% of the left ventricle), which was reduced by candesartan, 100 nM (12+/-1.3%; p < 0.05). In rats given candesartan, 1 nM, there was a trend toward a higher recovery of the double product (73+/-13.4%), a lower left ventricular end-diastolic pressure (29+/-6.6 mm Hg), and a smaller no-reflow area (19+/-3.5% of the left ventricle) compared with the rats receiving vehicle. These trends did, however, not reach statistical significance. Our results demonstrate that candesartan reduces myocardial ischemia/reperfusion injury, thus indicating that endogenous cardiac angiotensin II is involved in the tissue injury after myocardial ischemia and reperfusion.     

预防性口服氯化镁抗实验性心肌缺血作用的研究

目的观察预防性口服氯化镁对实验性心肌缺血的保护作用。方法用结扎清醒大鼠左冠状动脉（ＬＡＤ）前降支致急性心肌梗塞（ＡＭＩ）模型。结果预防性口服氯化镁能显著缩小心肌梗塞范围，降低血清磷酸肌酸激酶（ＣＰＫ）、天门冬氨酸氨基转移酶（ＡＳＴ）活性，提高血清钾、镁浓度，减轻清醒大鼠缺血早期心律失常。结论预防性口服氯化镁对心肌缺血损伤具有保护作用     

Therapeutic potential of fucoidan in myocardial ischemia

Fucoidan, a sulfated polysaccharide extracted from brown seaweed, is a candidate for the treatment of ischemic diseases. The aim of this study was to measure the therapeutic potential of fucoidan in a rat model of myocardial ischemia-reperfusion injury. Forty rats were submitted to myocardial ischemia-reperfusion injury by transient occlusion of the left coronary artery. Rats were then randomized into 2 groups: fucoidan (5 mg/kg, intramuscularly; n = 20) or control (saline intramuscularly; n = 20) was administered 1 hour before injury and daily thereafter for 1 month. At 1 month, plasma levels of stromal cell-derived factor-1α (SDF-1α) were assessed by enzyme-linked immunosorbent assay kit. Hearts were evaluated by histoimmunochemistry. Fucoidan induced significant antifibrotic effects, reducing the infarct scar size by almost 30% on Sirius red-stained sections (9.45% ± 4.27% vs. 13% ± 5.67% in controls; P = 0.03). Vascular density in the fucoidan group (α-actin, RECA-1, or lectin BS1 stained) was increased by 40% (2.18 ± 0.79 mm vs. 1.49 ± 0.42 mm in controls ×200; P = 0.001). Plasma SDF-1α at 1 month was not significantly different between the 2 groups. However, increased immunostaining density of SDF-1α and vascular endothelial growth factor in fibrotic ischemic tissues was observed in fucoidan-treated animals versus controls. In conclusion, fucoidan enhanced tissue repair in myocardial ischemia-reperfusion by promoting revascularization (in situ vascular endothelial growth factor and SDF-1α overexpression) and limiting fibrosis. Consequently, fucoidan may be useful for myocardial ischemic patients.