苦苣菜水提物对机体炎性反应相关通路的调节作用及其机制研究

目的:分析苦苣菜水提物对机体炎性反应相关通路的调节作用,并进一步对作用机制进行研究。方法:雄性健康SD小鼠100只,随机分成10组,每组10只,5组进行耳肿实验,5组进行足肿实验。耳肿实验与足肿实验中,分别设置模型组、地塞米松(2 mg/kg)阳性药物组、苦苣菜水提物0.26 g/10 g剂量组、苦苣菜水提物0.13 g/10 g剂量组、苦苣菜水提物0.065 g/10 g剂量组。检测不同组间血清及炎性组织液中COX-2、p38 MAPK、TNF-α及IL-6水平。结果:不同剂量组间小鼠耳廓肿胀度存在差异,各组肿胀抑制率分别为73.12%、43.62%、28.83%、9.61%。与模型组比较,苦苣菜水提物不同剂量组小鼠耳廓肿胀均受到不同程度的抑制,且随着给药剂量的增大,抑制效果逐渐增强。不同剂量组间小鼠足跖肿胀度存在差异;各组肿胀抑制率分别为54.80%、35.09%、29.73%、17.46%。与模型组比较,苦苣菜水提物不同剂量组小鼠足跖肿胀均受到不同程度的抑制,且随着给药剂量的增大,抑制效果逐渐增强。苦苣菜水提物对小鼠炎性组织液中炎性反应相关因子的影响:阳性对照组、苦苣菜水提物中剂量与高剂量组的COX-2、p38 MAPK、TNF-α、IL-6水平与模型组比较,差异有统计学意义(P0.05)。苦苣菜水提物对小鼠血清中炎性反应相关因子的影响:阳性对照组、苦苣菜水提物中剂量的COX-2、p38 MAPK水平与模型组比较,差异有统计学意义(P0.05);阳性对照组、苦苣菜水提物中剂量与高剂量组的TNF-α、IL-6水平与模型组比较,差异有统计学意义(P0.05)。结论:苦苣菜水提物的抗炎机制涉及到炎性反应发生过程中的多个环节和炎性反应因子,有望研发成为有效的抗炎新药,为防治炎性反应性疾病提供新的药用和食疗资源。     

小鼠同基因型移植物抗宿主病模型建立及其免疫机制初步探讨

目的：建立小鼠同基因型移植物抗宿主病模型，初步探讨小鼠同基因型移植物抗宿主病的免疫发生机制。方法：小鼠接受致死剂量的X线照射后，通过尾静脉注射同基因骨髓细胞进行骨髓移植和免疫重建，并于当天腹腔注射CsA进行诱导，连续21d。对照组小鼠腹腔注射相同体积和相同时间的橄榄油。停用CsA和橄榄油后观察小鼠是否出现同基因型移植物抗宿主病（SGVHD），若连续3次体重下降即可认为SGVHD阳性。取各组小鼠的肝脏、结肠、耳朵、皮肤和胸腺进行组织学检查；同时取小鼠的肝脏和结肠进行CD137mRNA和细胞因子IL-12、IFN-γ和TNF-αmRNA的检测。结果：CsA可诱导同基因型骨髓移植小鼠产生GVHD样症状，诱导组小鼠有67％出现SGVHD，而移植对照组未出现SGVHD。SGVHD阳性小鼠结肠和肝脏中CD137mRNA水平和IL-12、IFN-γ和TNF-αmRNA水平较移植对照组小鼠和诱导组中未出现SGVHD小鼠的水平升高，组织病理检查发现结肠和肝脏有大量炎细胞浸润。SGVHD阳性小鼠的胸腺大小与SGVHD呈负相关。结论：CsA可诱导X射线照射的同基因型骨髓移植小鼠产生SGVHD症状，CD137、细胞因子IL-12、IFN-7和TNF-α以及胸腺再生状态参与了SGVHD的病理机制。     

血管迷走性晕厥的机理及治疗进展

血管迷走性晕厥机制复杂。Bezold-Jarisch反射是最常见的激发机制。交感神经活性变化、5-羟色胺、肾素-血管紧张素系统和内皮功能异常等在发病中起重要作用。目前血管迷走性晕厥的治疗包括一般治疗、倾斜训练、药物治疗和起搏器治疗。     

胃肠动力检测方法及原理研究进展

功能性胃肠病是临床常见病,诊断常较困难.胃肠动力即消化道的自主运动力,包括肠的收缩运动、张力、顺应性、转运、室壁运动、室壁张力,它们协同作用完成:①推进功能,②混和功能,③储存功能,④防逆流功能.     

肿瘤热疗的细胞分子作用机制及应用进展

热疗是肿瘤治疗的有效手段之一,但是其作用机制长期不甚明了.近年来,随着热疗重新成为研究的热点之一,热疗的作用机制研究取得了很大进展.研究表明,亚高温热疗杀伤细胞以诱导细胞凋亡为主,而高温热疗则直接导致细胞坏死.热诱导凋亡通过线粒体或(和)死亡受体途径实现,氧化应激、胞内Ca~(2 )增高等诱导凋亡过程中起重要作用.基于热诱导细胞凋亡机制的一些联合治疗方法,如热疗联合基因治疗、氧化应激、Ca~(2 )靶向治疗以及降低细胞外pH值等可显著增强热疗作用.     

瘦素与冠心病

瘦素是肥胖基因编码的一种蛋白质产物,主要由白色脂肪组织分泌,通过与其受体结合发挥抑制食欲、减少能量摄入、增加能量消耗的生物学作用。大量临床研究表明冠心病患者常存在高瘦素血症,表现为瘦素抵抗。本文就瘦素在冠心病发病中的作用机制作一综述。     

Mitochondrial dysfunction and delayed hepatotoxicity: another lesson from troglitazone

Aims/hypothesis  Troglitazone was approved for treatment of type 2 diabetes mellitus, but by 2000 it had been removed from all world markets due to severe drug-induced liver injury. Even today, we still do not know how many patients sustained a long-term liver injury. No system is in place to acquire that knowledge. Regarding toxicity mechanisms, controversy persists as to which ones are class effects of thiazolidinediones (TZDs) and which are unique to troglitazone. This study aims to provide long-term outcome data and new insights on mechanisms of troglitazone-induced liver injury. Methods  This case series reports the liver injuries sustained by eleven type 2 diabetic patients treated with troglitazone between 1997 and 2000. Exhaustive review of medical records was performed for all patients. Long-term outcomes were available for all the non-fatal cases. A comprehensive literature review was also performed. Results  Long-term liver injury progressing to cirrhosis was identified in seven patients. All eleven cases had liver injury patterns consistent with troglitazone toxicity. Analysis of these cases and of the experimental troglitazone toxicity data points to mitochondrial toxicity as a central factor. The general clinical patterns of mitochondrial hepatotoxic events are reviewed, as are the implications for other members of the TZD family. Conclusions/interpretation  This analysis enables the liver injury induced by troglitazone to be better understood. In future cases of delayed drug-induced liver injury that progresses after discontinuation, the possibility of mitochondrial toxicity should be considered. When appropriate, this can then be evaluated experimentally. Such proactive investigation may anticipate clinical risk before a large-scale therapeutic misadventure occurs. Drug-induced liver injury due to mitochondrial hepatotoxins may be less unpredictable than has previously been surmised. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorised users.     

肺癌转移机制的研究进展

肺癌患者总生存率较低的主要原因是肿瘤细胞的转移.目前认为肺癌细胞的转移是一个非常复杂的过程,主要包括肺癌细胞离开原发灶、进入淋巴系统和血液系统、远处生长等方面.本文就肺癌转移的各个参与因素以及相关的新靶向药物的临床研究作一综述.     

The Pathophysiological Mechanisms of GERD in the Obese Patient

Obesity has increased dramatically in the last 30 years, affecting 33% of the adult population in the United States. Increase in body mass index has been shown to be associated with the increase in the prevalence of gastroesophageal reflux disease (GERD) symptoms, esophageal mucosal injury, and GERD complications. The putative mechanisms responsible for the close relationship between GERD and increased body mass index include increased intragastric pressure, increased gastroesophageal pressure gradient, esophageal motor and sensory abnormalities, increase in prevalence of hiatal hernia, increase in serum female hormonal levels, diet, and increase in comorbidities. Whilst the current efforts are to focus on one major underlying mechanism, it is highly likely that multiple factors contribute to the increased prevalence of GERD in the obese patient.