运动与心肌间质重塑研究进展

心脏重塑主要表现为心肌细胞肥大、细胞外间质重塑。细胞因子、基质金属蛋白酶家族对心肌间质重塑发挥较大的作用,参与了运动性心脏重塑的生理病理发展过程。近年来许多研究致力于阐明运动性心肌间质和血管重塑之间的关系。     

Traditional Chinese medicines and their active ingredients sensitize cancer cells to TRAIL-induced apoptosis

The rapidly developing resistance of cancers to chemotherapy agents and the severe cytotoxicity of such agents to normal cells are major stumbling blocks in current cancer treatments.Most current chemotherapy agents have significant cytotoxicity,which leads to devastating adverse effects and results in a substandard quality of life,including increased daily morbidity and premature mortality.The death receptor of tumor necrosis factor-related apoptosis-inducing ligand(TRAIL)can sidestep p53-dependent pathways to induce tumor cell apoptosis without damaging most normal cells.However,various cancer cells can develop resistance to TRAIL-induced apoptosis via different pathways.Therefore,it is critical to find an efficient TRAIL sensitizer to reverse the resistance of tumor cells to TRAIL,and to reinforce TRAIL’s ability to induce tumor cell apoptosis.In recent years,traditional Chinese medicines and their active ingredients have shown great potential to trigger apoptotic cell death in TRAIL-resistant cancer cell lines.This review aims to collate information about Chinese medicines that can effectively reverse the resistance of tumor cells to TRAIL and enhance TRAIL’s ability to induce apoptosis.We explore the therapeutic potential of TRAIL and provide new ideas for the development of TRAIL therapy and the generation of new anticancer drugs for human cancer treatment.This study involved an extensive review of studies obtained from literature searches of electronic databases such as Google Scholar and PubMed."TRAIL sensitize"and"Chinese medicine"were the search keywords.We then isolated newly published studies on the mechanisms of TRAIL-induced apoptosis.The name of each plant was validated using certified databases such as The Plant List.This study indicates that TRAIL can be combined with different Chinese medicine components through intrinsic or extrinsic pathways to promote cancer cell apoptosis.It also demonstrates that the active ingredients of traditional Chinese medicines enhance the sensitivity of cancer cells to TRAIL-mediated apoptosis.This provides useful information regarding traditional Chinese medicine treatment,the development of TRAIL-based therapies,and the treatment of cancer.     

Cardioprotective response to chronic administration of vitamin E in isoproterenol induced myocardial necrosis: Hemodynamic,biochemical and ultrastructural studies

The present study evaluated the cardioprotective potential of vitamin-E by studying its effect on hemodynamic parameters, lipid peroxidation, myocyte injury marker and ultrastructural changes in model of isoproterenol-induced myocardial necrosis in rats. Wistar albino male rats (150–200 g) were randomly divided into saline, ISP control, and vit E groups. Vitamin E group was administered vitamin E at a dose of 100mg/kg/day while saline and ISP control groups received saline orally for one month. On 29^th and 30^th day, ISP (85 mg/kg, sc) was administered at an interval of 24 h to vit E and ISP control rats. On 31^st day, rats of all groups were anesthetized and hemodynamic parameters were recorded. At the end of experimentation, animals were sacrificed; hearts were excised and processed for biochemical and ultrastructural studies. ISP administration produced marked cardiac necrosis as evidenced by significant decrease in my ocardial creatine kinase-MB as well as increase in malonaldialdehyde levels. ISP-induced myocardial necrosis resulted in myocardial dysfunction as evidenced by significant depression in heart rate and mean arterial pressure in the ISP control group as compared to saline control. Salient ultrastructural changes including extensive loss of myofibrils, muscle necrosis, loss of mitochondria, and formation of several intracytoplasmic vacuoles and lipid droplets further confirmed the ISP-induced myocardial damage. However, subsequent to ISP challenge, vit E treatment significantly preserved the myocardium by restoring myocardial CK-MB activity, inhibiting the ISP-induced lipid peroxidation and ultrastructural changes. Additionally, pre-and co-treatment of vit E prevented the deleterious ultrastructural changes caused by ISP. These beneficial effects of chronic vit E treatment also translated into significant restoration of the altered hemodynamic parameters. The present study clearly demonstrated the cardioprotective potential of vit E at dose of 100 mg/kg in ISP-induced model of myocardial necrosis in rats. The significant restoration of altered hemodynamic parameters, myocardial CK-MB activity, prevention of ISP-induced rise in lipid peroxidation and ultrastructural changes may confirm its cardioprotective effect.     

地塞米松可以减少由重症急性胰腺炎引起的肾脏微血管内皮糖萼的损伤（英文）

目的:明确地塞米松可以减少重症急性胰腺炎(SAP)引起的肿瘤坏死因子(TNF-α)的释放,减轻TNF-α导致的肾脏血管内皮糖萼的降解,从而改善肾脏微循环和缓解肾损伤。创新点:本研究通过小鼠活体研究的方法,建立小鼠重症急性胰腺炎模型,并用地塞米松进行干预对照,采用透射电镜、激光多谱勒和酶联免疫的方法,检测了各组小鼠肾脏血管内皮糖萼的完整性、肾血流灌注和TNF-α表达情况,阐明了地塞米松对内皮糖萼的保护作用。方法:通过"胰管结扎+腹腔内雨蛙素注射"的方法建立SAP模型,分别留取各组小鼠的血液和组织标本,采用透射电镜观察内皮糖萼的损伤情况,用酶联免疫检测血清TNF-α和糖萼成份多配体聚糖的浓度,并用激光多谱勒检测活体小鼠肾脏的灌注,分析地塞米松对内皮糖萼的保护和改善肾脏灌注的作用。结论:SAP可以引起TNF-α的大量释放,并导致内皮糖萼的降解和肾脏灌注下降,而地塞米松可以减少TNF-α的释放,减轻糖萼的降解,改善肾脏血流灌注。     

氟伐他汀对不稳定型心绞痛患者血清白介素-18和肿瘤坏死因子α干预的研究

目的研究氟伐他汀对不稳定型心绞痛患者血清白介素-18（IL-18）和肿瘤坏死因子α（TNFα）的影响。方法选择2006年9月至2007年7月79例不稳定型心绞痛患者,入院后随机分为2组：氟伐他汀干预组42例：常规药物治疗基础上加用氟伐他汀40mg／d;对照组37例：常规药物治疗。分别于药物治疗前、药物治疗后2周采集静脉血,测定血清IL-18和TNFα的浓度。结果药物治疗后,对照组（P〈0．05）及氟伐他汀干预组（P〈0．01）血清IL-18和TNF＆浓度均明显降低;氟伐他汀干预组血清IL-18（P〈0．01）和TNFα（P〈0．01）浓度明显低于同期对照组。结论氟伐他汀可明显降低不稳定型心绞痛患者血清IL-18和TNFα浓度。     

运动性疲劳与细胞凋亡

细胞凋亡是由基因调控的细胞死亡过程,它对于多细胞生物的生存和发展以及维持其自身的稳定有极其重要的作用。通过查阅资料,对各种实验模型中运动或类似运动而引起的细胞凋亡进行总结,试图从中发现运动性疲劳与细胞凋亡的关系,以便为运动性疲劳的判断和恢复、运动损伤的尽快修复提供一定的指导。     

Role of Cytokines in the Pathogenesis of Non-Alcoholic Fatty Liver Disease

A number of factors are linked with non-alcoholic fatty liver diseases (NAFLD), a condition that ranges from clinically benign fatty liver to its more severe form, non alcoholic steatohepatitis (NASH). In this study, we evaluated the role of cytokines secreted from adipose tissue in the pathogenesis and progression of NAFLD. We also compared anthropometric profile, lipid profile and insulin resistance data in 105 NAFLD patients with 77 normal subjects. These subjects showed a normal serum albumin level, prothrombin time and renal function but elevated aminotransferases. Predisposing factors were diabetes mellitus (35%), overweight (56%) and hyperlipidemia (44%). Insulin resistance (IR), determined by homeostasis model assessment (HOMA) was confirmed in 70% patients with NAFLD and 42% patients fulfilled the minimum criteria for insulin resistance syndrome (IRS). NAFLD patients showed elevated levels of pro-inflammatory cytokines tumor necrosis factor (TNF)-α, and interleukin (IL)-6, while anti-inflammatory cytokines IL-4 level decreased and IL-10 level remain unchanged; however, TGF-β1 level elevated significantly compared to normal subjects. While insulin level and HOMA-IR both were significantly positively correlated with BMI, waist-to-hip ratio, total cholesterol, VLDL-cholesterol, triglyceride and TGF-β1; glucose, IL-6 and TNF-α levels were significantly positively correlated with HOMA-IR only. In conclusion, pro-inflammatory cytokines play an important link between metabolic and liver disorders in the fat accumulation, and thereby cause IR, inflammation and liver fibrosis.     

Extracellular Methemoglobin Mediated Early ROS Spike Triggers Osmotic Fragility and RBC Destruction: An Insight into the Enhanced Hemolysis During Malaria

Malaria infection is known to cause severe hemolysis due to production of abnormal RBCs and enhanced RBC destruction through apoptosis. Infected RBC lysis exposes uninfected RBC to the large amount of pro-oxidant molecules such as methemoglobin. Methemoglobin (MetHb) exposure dose dependently makes RBCs susceptible to osmotic stress and causes hemolysis. MetHb mediated oxidative stress in RBC correlated well with osmotic fragility and hemolysis. Interestingly, a reactive oxygen species (ROS) spike at 15 min was responsible for the observed effects on RBC cells. Two natural antioxidants N-acetyl cysteine and mannitol protected the RBC from MetHb-mediated defects, which clearly indicated involvement of oxidative stress in the process. MetHb due to its pseudo-peroxidase activity produces ROS in the external microenvironment. Therefore, classical peroxidase inhibitors were tested to probe peroxidase activity mediated ROS production with defects in RBCs. Clotrimazole (CLT), which irreversibly inactivates the MetHb (CLT-MetHb) and abolishes peroxidase activity, did not produce significant ROS outside RBC and was inefficient to cause osmotic fragility and hemolysis. Hence, initiating a chain reaction, MetHb released from ruptured RBC produces significant ROS in the external microenvironment to make RBC membrane leaky and enhanced hemolysis. Together data presented in the current work explored the role of MetHb in accelerated humorless during malaria which could be responsible for severe outcomes of pathological disorders.     

日本对虾爆发性流行病病原体的调查

采用石蜡切片和电镜技术检测了发病塘的养成期日本对虾（Ｐｅｎａｅｕｓｊａｐｏｎｉｃｕｓ）２０尾,发现２尾感染了斑节对虾杆状病毒,１１尾感染了日本对虾中肠腺坏死杆状病毒（ＢＭＮＶ）．结果表明,日本对虾的发病主要由ＢＭＮＶ感染所致     

细胞凋亡、坏死、自噬的检测方法与技术

目前普遍认为细胞的死亡途径有细胞凋亡、细胞坏死及自噬3种,其中细胞凋亡一直是医学界为治疗癌症而不懈努力研究的方向,而自噬是近几年研究的热点.现对这3种死亡方式及其各自的检测方法作一简要概述.