Protective effects of caffeic acid phenethyl ester (CAPE) on carbon tetrachloride-induced hepatotoxicity in rats

In the present study, protective effects of caffeic acid phenethyl ester (CAPE) have been evaluated on carbon tetrachloride (CCl4)-induced hepatotoxicity in rat. Twenty-four male Wistar rats were divided in three groups. Group I was used as control. Rats in group II were injected every other day with CCl4 for 1 month, whereas rats in group III were injected every other day with CCl4 and CAPE for 1 month. At the end of the experiment, all animals were killed by decapitation and blood samples were obtained. Serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total and conjugated bilirubin levels and hepatic malondialdehyde (MDA) contents were determined. For histopathological evaluation, livers of all rats were removed and processed for light microscopy. All biochemical parameters in serum and the hepatic MDA content were significantly higher in animals treated with CCl4 than in the controls. Rats treated with CCl4 and CAPE showed a significant reduction in biochemical parameters in serum and hepatic MDA content. Livers of rats treated with CCl4 showed classic histology of cirrhosis, whereas the histopathological changes were reduced after administration of CCl4 and CAPE. A normal lobular appearance was observed in livers in this group except for fatty degeneration. The results of our study indicate that CAPE treatment prevents CCl4-induced liver damage in rats.     

Lithium-induced lung toxicity in rats: the effect of caffeic acid phenethyl ester (CAPE)

AIMS: We aimed to evaluate the effects of caffeic acid phenethyl ester (CAPE) on lithium (Li)-induced lung toxicity. METHODS: Twenty-two adult male Wistar albino rats weighing between 280 and 300 g were used. The rats were randomly divided into three groups: control, Li and Li+CAPE groups. Li and CAPE were co-administered intraperitoneally twice daily for 4 weeks. Control rats were given 0.9% NaCl during the same period. All the rats were allowed to feed ad libitum until midnight after they had received the proposed treatment. RESULTS: In the Li group, peribronchial and intraparenchymal lymphocyte and macrophage infiltration were observed. Atypical type II pneumocytes, alveolar destruction and emphysematous changes were also detected. Lymphocyte and macrophage infiltration was significantly decreased in the Li+CAPE group compared with the Li group. Alveolar destruction, emphysematous changes and intraparenchymal mononuclear cell infiltration were also recovered to a level close to the control group. Malondialdehyde (MDA) levels were increased in the Li group compared with the control group. CAPE administration decreased the MDA levels in the Li+CAPE group. CONCLUSIONS: CAPE was found to associate with histopathological changes recovery in the lungs and oxidative stress due to Li treatment.     

The neuroprotective effects of caffeic acid phenethyl ester (CAPE) in the hippocampal formation of cigarette smoke exposed rabbits

BACKGROUND: In this study, the neuroprotective effects of caffeic acid phenethyl ester (CAPE) in the hippocampus of cigarette smoke exposed rabbits were investigated. MATERIALS AND METHODS: Eighteen rabbits were used as experimental subjects and divided into three equal groups. The control group (Group A) was exposed to clean air. Rabbits in the cigarette smoke (CS) group (Group B) were exposed to cigarette smoke 1 hour daily in a room within a glass chamber for 4 weeks. Animals in the CS+CAPE group (Group C) were exposed to cigarette smoke as in Group B and administered CAPE (10 micromol/kg/day) intraperitoneally for 4 weeks just before the exposure to cigarette smoke. Rabbits in all three groups were sacrificed with intraperitoneal administration of 100 mg/kg sodium pentothal and their brains were removed immediately. In the hippocampal formation samples of left hemispheres, the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were measured and the number of apoptotic neurons was counted by 'terminal transferase dUTP nick end labelling' (TUNEL) assay in the right hippocampal formation. RESULTS: We found that MDA levels increased significantly in the Group B rabbits compared with the control group (Group A; p = 0.001). In contrast, SOD activities decreased significantly in Group B rabbits compared with the control group (p = 0.001). In the CAPE treated rabbits (Group C), MDA levels decreased and SOD activities increased significantly as compared with Group B rabbits (p = 0.002, p = 0.002, respectively). The number of apoptotic neurons (TUNEL+) in the CA1, CA2, CA3 and dentate gyrus areas of rabbits' hippocampal formation were significantly increased in Group B rabbits compared with the control group. On the other hand, the number of apoptotic neurons in the hippocampus areas was decreased significantly in Group C rabbits compared with Group B rabbits. CONCLUSION: These findings suggest that cigarette smoking induces apoptosis in the hippocampal formation of rabbits and CAPE has a protective role against this induction.     

促红细胞生成素减轻大鼠心肌缺血再灌注损伤

目的探讨促红细胞生成素在心肌缺血再灌注损伤中对细胞外基质代谢的调节作用及其机制。方法构建Langendroff大鼠离体心脏缺血再灌注模型,结合Western blot观测在促红细胞生成素及相应信号传导通路阻滞剂干预下,左室舒张末压(LVEDP)、梗死面积、MMPs及胶原Ⅰ/Ⅲ表达的变化。结果促红细胞生成素可改善LVEDP[(19.8±0.2)mmHgvs(35.9±0.2)mmHg,IR组vsEPO+IR组,P<0.05],减少梗死面积(35.26%±7.1%vs62.70%±7.2%,EPO+IR组vsIR组,P<0.05)。在缺血再灌注损伤的过程中MMP2及MMP9表达均显著升高,而TIMP-4则显著减低。外源性EPO可逆转MMPs的激活。此外EPO则可促进胶原Ⅲ、Ⅰ的表达,并且这一保护作用可被MEK-Erk信号通路阻滞剂所阻断。结论EPO通过MEK-Erk信号传导通路促进胶原Ⅰ/Ⅲ的合成,抑制MMPs的激活,抑制细胞外基质降解,在一定程度上减轻大鼠心肌缺血再灌注损伤。     

PEP-1-CAT融合蛋白预处理减轻在体大鼠心肌缺血再灌注损伤

氧自由基学说是心肌缺血再灌注损伤的关键性机制.过氧化氢酶(eatalase,CAT)是机体三大抗氧化酶之一,但它是生物大分子,不能有效穿透细胞,从而限制了它在缺血再灌注损伤防治中的应用.利用基因工程手段纯化出了PEP-1-CAT融合蛋白,且成功将此蛋白转导入细胞内,明显减轻了过氧化氢诱导细胞的氧化损伤[1].本实验利用在体大鼠,探讨PEP-1-CAT融合蛋白预处理对在体大鼠心肌缺血再灌注损伤的保护作用.     

Class 3 inhibition of hERG K+ channel by caffeic acid phenethyl ester (CAPE) and curcumin

Human ether-á-go-go-related gene (hERG) K⁺ channel current (I _hERG ) is inhibited by various compounds and genetic mutations, potentially resulting in cardiac arrhythmia. Here, we investigated effects of caffeic acid phenethyl ester (CAPE) and curcumin, two natural anti-inflammatory polyphenols, on I _hERG in HEK-293 cells overexpressed with hERG. CAPE dose-dependently decreased repolarization tail current of hERG (I _hERG,tail; IC₅₀, 10.6?±?0.5 μM). CAPE also shifted half-activation voltage (V _1/2) to the left (from ?17.5 to ?26.5 mV) and accelerated activation and inactivation kinetics. The CAPE inhibition of I _hERG,tail was not attenuated in the pore-blocker site mutants of hERG (Y652A and F656A). A point mutation of Cys723 (C723S) mimicked the effects of CAPE and caused a left shift of V _1/2 and acceleration of I _hERG,tail deactivation. However, I _hERG,tail inhibition by CAPE was still observed in C723S. Taken together, CAPE inhibits hERG channel by class 3 mechanism, i.e., modification of gating, not by blocking the pore. Curcumin induced changes of I _hERG similar to those of CAPE, while additional interaction with pore-blocking sites was suggested from attenuated I _hERG,tail inhibition in Y652A and F656A. Interestingly, I _hERG induced by human action potential voltage clamp was increased by CAPE while decreased by curcumin. Mathematical simulation of action potential derived from the experimental results of CAPE and curcumin supports that CAPE, but not curcumin, would induce shortening of AP duration by facilitation of I _hERG . The above results revealed intriguing roles of Cys723 in hERG kinetics and suggested that conventional drug screening by using step pulse protocol for I _hERG,tail would overlook the hERG kinetic modulations that could compensate the decrease of I _hERG,tail.     

Cancer prevention mediated by caffeic acid phenethyl ester involves cyp2b1/2 modulation in hepatocarcinogenesis

Studies of cancer chemoprevention with caffeic acid phenethyl ester (CAPE) in the resistant hepatocyte model of hepatocarcinogenesis have shown the participation of CYP drug metabolizing enzymes. To prevent neoplastic and preneoplasic lesions, we must specifically identify which CYP activities are modified in the mechanism of action of CAPE. Male Fischer-344 rats were pretreated with CAPE twelve hours before administration of diethylnitrosamine (DEN) and were sacrificed twelve hours after CAPE and twelve hours, twenty-four hours, twenty-four days, and twelve months after DEN. Other rats were treated with the CYP inhibitors α-naphthoflavone or SKF525A and sacrificed twenty-four hours and twenty-four days after DEN. Microsomes were obtained from livers to quantify protein using Western blot. Diethylnitrosamine metabolism was measured based on nitrite formation and liver histology using GGT histochemistry. Caffeic acid phenethyl ester diminished the protein levels of CYP1A2 and CYP2B1/2. The inhibition of CYP2B1/2 prevented the appearance of preneoplastic lesions. Microsomal assays demonstrated that CAPE interfered with DEN activation diminishing nitrites similar to SKF525A and probably mediated by CYP2B1/2 inhibition. A single dose of CAPE before DEN treatment reduced the appearance of tumors by 43%. These results confirmed that CAPE is a promising agent to confer chemoprotection in liver cancer and should be considered for human therapies.     

Glycine attenuates myocardial ischemia-reperfusion injury by inhibiting myocardial apoptosis in rats

Glycine is a well-documented cytoprotective agent.However,whether it has a protective effect against myocar-dial ischemia-reperfusion injury in vivo is still unknown.By using an open-chest anesthetized rat model,we found that glycine reduced the infarct size by 21% in ischemia-reperfusion injury rats compared with that in the vehicle-treated MI/R rats.The left ventricular ejection fraction and fractional shortening were increased by 19.11% and 30.98%,respectively,in glycine-treated rats.The plasma creatine kinase levels in ischemia-reperfusion injury rats decreased following glycine treatment.Importantly,administration of glycine significantly inhibited apoptosis in post-ischemia-reperfusion myocardium,which was accompanied by suppression of phosphorylated p38 mitogen-activated protein kinase and c-Jun NH2-terminal kinase,as well as the Fas ligand.These results suggest that gly-cine attenuates myocardial ischemia-reperfusion injury in vivo by inhibiting cardiomyocytes apoptosis.     

Bmal1对糖尿病大鼠心肌缺血再灌注损伤的影响及其相关机制

目的 探讨Bmal1对糖尿病大鼠心肌缺血再灌注损伤的影响及其相关机制。方法 选择健康雄性清洁级SD大鼠65只,采用数字表法随机纳入非糖尿病假手术组（N-S组）10只、非糖尿病缺血再灌注组（N-I/R组）10只、非糖尿病+SR8278缺血再灌注组（NS-I/R组）10只;剩余35只采用高脂饲料喂养+腹腔注射链脲佐菌素方法制备2型糖尿病模型,取造模成功的大鼠30只,采用数字表法随机分为糖尿病假手术组（DM-S组）、糖尿病缺血再灌注组（DM-I/R组）、糖尿病+SR8278缺血再灌注组（DMS-I/R组）,每组10只。6组大鼠按观察项目不同随机分为A、B亚组,每组5只。各组大鼠制备心肌缺血再灌注模型,其中N-S组和DM-S组仅模拟手术过程,不结扎前降支;NS-I/R组、DMS-I/R组大鼠于心肌缺血再灌注模型制备前7天开始腹腔注射孤儿核受体Rev-erbα拮抗剂SR8278（50 mg/kg）,每天1次×7 d。心肌缺血再灌注模型成功后维持灌注24 h,取各组A亚组大鼠,分离出左心室行病理染色检查和心肌超微结构透射电镜观察,分离左心室后的心脏制备病理切片进行心肌梗死灶体积的测定;各组B亚组大鼠,取心尖区心肌组织行Western blot测定心肌Bmal1、Sirt3、Nlrp3及Bnip3蛋白的表达。结果 （1） N-S组和DM-S组未见心肌梗死灶,N-I/R组、NS-I/R组、DM-I/R组、DMS-I/R组心肌梗死灶体积分别为（0.48±0.08）cm³、（0.34±0.05）cm³、（0.65±0.06）cm³、（0.46±0.06）cm³。与N-I/R组比较,NS-I/R组心肌梗死灶体积较小,DM-I/R组较大,差异均有统计学意义（P值均<0.05）;与NS-I/R组比较,DM-I/R组、DMS-I/R组心肌梗死灶体积均较大,差异均有统计学意义（P值均<0.05）;与DM-I/R组比较,DMS-I/R组心肌梗死灶体积较小,差异有统计学意义（P<0.05）。（2）心肌组织病理检查：N-S组心肌组织结构完整,心肌细胞排列整齐、致密,细胞质染色均匀;DM-S组心肌纤维排列稍紊乱,细胞质有轻度的肿胀,可见轻度炎性细胞浸润;N-I/R组细胞形态不规则,心肌纤维排列紊乱或断裂,细胞质有不同程度的肿胀甚至破裂,胞核排列不齐、碎裂和溶解;DM-I/R组心肌病理损伤程度较N-I/R组更重,心肌纤维断裂,心肌细胞崩解,细胞核溶解,染色加深,可见大量炎细胞浸润。与N-I/R组和DM-I/R组相比,NS-I/R组和DMS-I/R组心肌细胞形态和心肌纤维排列有所恢复,炎性细胞浸润大大减少。（3）电子显微镜下心肌组织超微结构：N-S组线粒体形态及数量正常,未见自噬体;DM-S组较N-S组出现自噬小体;N-I/R组心肌细胞中正常线粒体数量减少,线粒体明显肿胀并含有大量自噬体,一些自噬体显示出封装未降解的线粒体结构和残留的细胞成分。与N-I/R组相比,NS-I/R组线粒体结构较完整,线粒体轻度肿胀,损伤较轻;DM-I/R组线粒体嵴结构异常,线粒体嵴分隔、肿胀和溶解,线粒体面积/周长比增加,线粒体自噬功能受损,自噬体增加。与DM-I/R组比较,DMS-I/R组肌纤维排列较为整齐,线粒体中结构异常的线粒体嵴减少,自噬体数量减少。（4）心肌组织Bmal1、Sirt3、Nlrp3及Bnip3蛋白表达水平。与N-S组比较,N-I/R组、NS-I/R组、DM-S组、DM-I/R组、DMS-I/R组Bmal1、Sirt3蛋白的表达呈下降趋势,Nlrp3、Bnip3蛋白的表达呈上升趋势,差异均有统计学意义（P值均<0.05）。与DM-S组比较,DM-I/R组Bmal1、Sirt3蛋白表达下调,Nlrp3、Bnip3蛋白表达上调;DMS-I/R组Nlrp3蛋白表达下调,Bnip3蛋白表达上调：差异均有统计学意义（P值均<0.05）。与DM-I/R组比较,DMS-I/R组Bmal1、Sirt3、Bnip3蛋白表达上调,Nlrp3蛋白表达下调,差异均有统计学意义（P值均<0.05）。结论 Bmal1在大鼠糖尿病心肌缺血再灌注损伤中对心肌有保护作用,其保护机制可能与激活Sirt3途径诱导线粒体自噬和抑制炎性反应有关。     

α-硫辛酸对大鼠肾缺血再灌注损伤的影响

目的： 探讨硫辛酸（LA）对大鼠肾缺血再灌注损伤(RIRI)的作用及其机制。方法: 采用夹闭双侧肾动、静脉45 min后松夹再灌的方法制作RIRI模型，测定血清肌酐（Scr）、丙二醛(MDA)、一氧化氮(NO)及尿NAG酶(UNAG)浓度，放射免疫和免疫组化法对肾皮质内皮素-1（ET-1）的表达做定位和定量分析，肾组织病理学观察和流式细胞术检测肾损伤程度和肾皮质细胞凋亡率。结果： 缺血再灌注后，大鼠肾功能和肾小管上皮细胞明显受损，Scr、MDA和UNAG含量均明显高于sham组(P<0.01)，血清NO含量与sham组相比无明显差异；肾皮质ET-1含量明显高于sham组(P<0.01)，肾小管ET-1表达明显强于sham组，ET-1免疫反应阳性颗粒主要分布于近曲小管上皮细胞；肾皮质细胞凋亡率明显高于sham组(P<0.01)。尾静脉注射α-硫辛酸可明显降低RIRI大鼠Scr、MDA和UNAG水平，肾小管上皮细胞内ET-1免疫反应阳性颗粒明显少于IR组，肾皮质细胞凋亡率明显低于IR组(P<0.05)。结论： ET-1在大鼠RIRI的发生发展中起着十分重要的作用；LA可通过拮抗ET-1的生物学效应，减轻氧自由基损伤而对RIRI大鼠肾脏产生一定的保护作用。     

虫草素预处理减轻SD大鼠心肌缺血再灌注损伤

目的:研究大鼠心肌缺血再灌注(IR)损伤中,虫草素(cordycepin,Cordy)能否通过调节微小RNA-455(miR-455)的表达和减少内质网应激(endoplasmic reticulum stress,ERS)引起的凋亡发挥心肌保护作用。方法:体重250~300 g的SD大鼠随机分为3组:对照(control)组,大鼠只进行开胸手术;IR组,大鼠心肌缺血30 min,再灌注120 min;虫草素治疗组(IR+Cordy组):大鼠缺血再灌注前给予虫草素(10 mg/kg)股静脉注射,每天1次,共注射1周。全自动化学分析法检测大鼠血清中乳酸脱氢酶(LDH)和肌酸激酶同工酶MB(CK-MB)活性。TUNEL试剂盒检测心肌内皮细胞(endothelial cells,EC)凋亡率,电镜观察EC超微结构的改变。RT-q PCR法检测心肌组织miR-455及ERS介导的细胞凋亡信号通路的标志物葡萄糖调节蛋白78(glucose-regulated protein 78,Grp78)和caspase-12的mRNA表达。结果:与control组比较,IR组EC的凋亡率明显升高(P0.05);与IR组比较,虫草素组EC的凋亡率明显下降(P0.05)。与control组比较,IR组的EC线粒体肿胀,膜不规整,内皱疏松有空泡,基粒消失,核膜不规整,染色质浓集、边集,核仁消失,甚至出现凋亡小体;IR+Cordy组与IR组比较症状大为改善。与control组比较,IR组心肌组织Grp78和caspase-12的mRNA及miR-455含量均升高(P0.05);与IR组比较,IR+Cordy组Grp78和caspase-12的mRNA及miR-455的含量均降低(P0.05)。结论:虫草素可有效减轻心肌IR后大鼠心肌EC凋亡,降低心肌组织miR-455表达,抑制内质网应激。     

Antioxidant activity of CAPE (caffeic acid phenethyl ester) in vitro can protect human sperm deoxyribonucleic acid from oxidative damage

Purpose

Sperm processing (e.g., centrifugation) used in preparation for assisted reproduction can result in excessive generation of reactive oxygen species (ROS) and potential sperm damage. The use of antioxidants during sperm processing has been shown to prevent iatrogenic sperm damage, including DNA damage. In this study, we evaluated the effect of caffeic acid phenethyl ester (CAPE) on oxidative stress mediated sperm dysfunction and DNA damage.

二巯丙磺钠对大鼠脑缺血再灌注损伤的保护作用

目的 :探讨二巯丙磺钠 (Na DMPS)对大鼠脑缺血再灌注损伤的保护作用。方法 :用复制大鼠 4 动脉阻断模型 ,观察脑缺血再灌注损伤的水份和钙含量变化及组织学和超微结构改变 ,以及Na DMPS脑室内给药 (icv)对上述指标的影响。结果 :脑缺血 2 0min ,再灌注 60min ,可造成脑水份 ,钙含量明显增加 ,组织形态学检查亦见缺血再灌注损伤。缺血前 2 0minicvNa DMPS 90 0 μg·kg 1,能显著降低脑水份和钙含量 ,逆转脑缺血再灌注损伤。结论 :Na DMPS对大鼠脑缺血再灌注损伤有保护作用。     

In vivo responses of macrophages and myofibroblasts in the healing following isoproterenol-induced myocardial injury in rats

To clarify the relation between macrophage and myofibroblast involvement in various myocardial diseases, the authors investigated the kinetics of these cells in the healing (scar tissue formation) following isoproterenol-induced myocardial injury in rats. Alphasmooth muscle actin (-SMA) expressing myofibroblasts were seen at the border of the affected area and appeared in the greatest numbers on days 3–7 post-injection, followed by a gradual decrease by day 35. The peak on day 3 was consistent with the timing of the highest proliferative activity of myofibroblasts. The number of ED1-positive macrophages began to increase as early as day 1, reaching a peak on day 3 within the injured myocardium. The expansion of EDI-positive macrophages preceded an increased number of -SMA-positive myofibroblasts suggesting that myofibroblast proliferation and activation may be mediated by factors released by ED1-positive mcrophages in response to myocardial injury. The number of ED2-positive tissue-fixed, resident macrophages gradually increased from day 3 post-injection, and peaked on day 14, but the number of ED2-positive macrophages was consistently fewer than that of ED1-positive macrophages during the 35 day-observation period after the injection. The labelling index of the ED2-positive cells was maximal on day 14, indicative of local proliferation of resident macrophages. In the healing process after myocardial injury, EDI-positive macrophages increase markedly in the early stages; ED2-positive macrophages appear later.     

胰高血糖素样肽-1对大鼠心肌缺血再灌注/细胞缺氧复氧损伤的保护作用及机制

目的: 观察胰高血糖素样肽-1(GLP-1)对大鼠心肌缺血再灌注/细胞缺氧复氧损伤的作用并探讨其机制。方法: 建立大鼠缺血再灌注模型,分别设假手术组(sham)、缺血再灌注组(IR)和IR + GLP-1(0.030 nmol/L、0.16 nmol/L和0.30 nmol/L)组,缺血30 min后再灌注3 h,Evan’s blue-TTC法检测心肌梗死范围;取左心室游离壁心肌组织,TUNEL法检测心肌细胞凋亡,同时测定心肌组织中氧化-抗氧化物质超氧化物歧化酶(SOD)活性及丙二醛(MDA)含量;培养乳鼠心肌细胞,随机分为正常对照组(control)、单纯缺氧复氧组(HR)、HR + GLP-1(1 μmol/L、5 μmol/L和10 μmol/L)组,电镜下观察心肌细胞形态的变化,流式细胞术检测心肌细胞的凋亡,测定乳酸脱氢酶(LDH)释放、SOD活性、MDA含量、活性氧簇(ROS)水平以及线粒体膜电位(MMP)。结果: 与IR组相比,IR+GLP-1(0.03 nmol/L、0.16 nmol/L和0.30 nmol/L)组剂量依赖性地减小心肌梗死面积,减轻线粒体超微结构改变及细胞凋亡,增加SOD活性,减少MDA含量(P<0.05 或P<0.01);与HR组相比,HR+GLP-1(1 μmol/L、5 μmol/L和10 μmol/L)组剂量依赖性地逆转HR诱导的细胞损伤,增加SOD活性,减少MDA含量,降低ROS水平,减轻HR诱导的MMP降低(P<0.05或P<0.01)。结论: GLP-1可以减轻大鼠心肌缺血再灌注/细胞缺氧复氧损伤;其作用机制可能与增强心肌抗氧化能力及保护线粒体结构和功能有关。     

阿魏酸川芎嗪对缺血再灌注大鼠心肌细胞凋亡及凋亡相关蛋白表达的影响

 目的：观察阿魏酸川芎嗪对缺血再灌注损伤大鼠心肌细胞凋亡的影响,并探讨其可能机制。方法：将60只雄性SD大鼠随机分成5组：（1）假手术组;（2）缺血再灌注组;（3）川芎嗪(4 mg/kg)组;（4）阿魏酸川芎嗪低剂量(4 mg/kg)组;（5）阿魏酸川芎嗪高剂量(8 mg/kg)组。采用结扎左冠状动脉前降支30 min、再灌注120 min的方法复制大鼠心肌缺血再灌注模型;各组大鼠于再灌注前10 min分别颈静脉注射给药,于再灌注结束后,进行血清生化及心肌组织学检测。结果：阿魏酸川芎嗪能显著降低心肌缺血再灌注损伤大鼠血清中肌酸激酶同功酶、乳酸脱氢酶、心肌钙蛋白I和丙二醛的水平,提高总超氧化物歧化酶活性,增加心肌Bcl-2蛋白的表达,减少心肌Bax蛋白的表达, 提高Bcl-2/Bax 的比值和降低心肌细胞凋亡指数,与缺血再灌注组比较,差异有统计学意义（P＜0.01）。阿魏酸川芎嗪各项指标优于川芎嗪（P＜0.05或P＜0.01）。结论：阿魏酸川芎嗪能减轻大鼠心肌缺血再灌注损伤;其抗缺血再灌注诱导的心肌细胞凋亡的机制可能与其上调Bcl-2蛋白和下调Bax蛋白表达有关。     

内皮素与一氧化氮在2型糖尿病大鼠心肌缺血再灌注损伤中的变化及意义

目的 探讨血清内皮素(ET)-1、一氧化氮(NO)在2型糖尿病大鼠心肌缺血再灌注损伤过程中的变化及意义.方法 选择体重160 ～ 180 g的健康雄性Wistar大鼠,采用高脂饲养联合腹腔注射链脲佐菌素(STZ)的方法制备2型糖尿病模型,取造模成功后的糖尿病大鼠14只(D组),随机分为两组(n=7):糖尿病心肌缺血再灌注组(DI组)和糖尿病假手术组(DC组).年龄匹配的健康雄性Wistar大鼠14只作为对照(C组),随机分为两组(n=7):心肌缺血再灌注组(CI组)和假手术组(CC组).DI组和CI组采用结扎左冠状动脉前降支30 min再灌注120 min的方法制备心肌缺血再灌注模型.各组分别测定基础状态、再灌注120 min时血清NO、ET-1的含量.结果 与基础状态时比较,CI组、DI组在缺血再灌注120 min时血清NO水平降低、ET-1水平升高(t值分别为4.96、4.69、19.04和3.35,P＜0.05).与CC组比较,CI组NO水平降低、ET-1水平升高,差异具有统计学差异(F=18.07、11.97,P＜0.05);与DC组比较,DI组NO水平降低、ET-1水平升高具有统计学差异(F=4.15、8.04,P＜0.05).DC组基础状态时血清ET-1水平高于CC组,具有统计学差异(=9.47,P＜0.05).结论 血清中NO、ET-1在2型糖尿病大鼠心肌缺血再灌注损伤的病理生理过程中具有一定的意义.     

The effects of selenium against cerebral ischemia-reperfusion injury in rats

It is known that the brain tissue is extremely sensitive to ischemia-reperfusion (IR) injury and therefore, brain ischemia and consecutive reperfusion result in neural damage and apoptosis. The proinflammatory cytokines such as tumor necrosis factor alfa (TNF-α) and interleukin-1 beta (IL-1β) are produced during neurological disorders including cerebral ischemia. On the other hand, nerve growth factor (NGF), which is essential for the differentiation, survival and functions of neuronal cells in the central nervous system, regulate neuronal development through cell survival and cell death signaling. In the present study, we aimed to investigate the effect of selenium (Se) on prefrontal cortex and hippocampal damage in rats subjected to cerebral IR injury. Selenium was injected intraperitoneally at the doses of 0.625 mg/(kg day) after induction of IR injury. Prefrontal cortex and hippocampal damage was examined by cresyl-violet staining. Apostain and caspase-3 immune staining were used to detect apoptosis. TNF-α, IL-1β and NGF levels were also evaluated. Histopathological evaluation showed that treatment with selenium after ischemia significantly attenuated IR-induced neuronal death in prefrontal cortex and hippocampal CA1 regions of rats. Apoptotic cells stained with apostain and caspase-3 were significantly decreased in treatment group when compared with the IR group. Additionally, treatment with selenium decreased the TNF-α and IL-1β levels and increased the NGF levels in prefrontal cortex and hippocampal tissue of animals subjected to IR. The present results suggest that selenium is potentially a beneficial agent in treating IR-induced brain injury in rats.     

川芎嗪对缺血再灌注所致大鼠离体心脏损伤的保护作用

目的:观察川芎嗪对缺血再灌注所致大鼠离体心脏损伤的保护作用。方法:心脏缺血再灌注模型:大鼠离心脏Langen-dorff灌流,全心停灌20分钟后复灌40分钟造成缺血--再灌注损伤。将充水乳胶球囊通过左心房插入左心室,Medlab-u/81生物信号采集处理系统记录分析心功能指标LVP,±dp/dtmax,HR和CF,收集再灌5分钟时,冠脉流出液。用分光光度法测定肌酸激酶(CK)活性。结果:缺血再灌注能降低冠脉流量,LVP,±dp/dtmax值,减慢心率、增加CK释放量,两个浓度的川芎嗪(40与80mg·L-1)对离体大鼠心脏缺血再灌注损伤有保护作用,表现为改善心功能,增加冠脉流量,减少心肌细胞内酶CK的释放,川芎嗪与维拉帕米有相似的心肌保护作用。结论:川芎嗪对心脏缺血再灌注心功能损伤具有保护作用。