细胞自噬在肝纤维化中的作用

细胞自噬是细胞内的一种代谢过程,通过细胞内的膜结构包裹部分胞质和细胞内需降解的细胞器、蛋白质等形成自噬小体,然后与溶酶体融合降解其所包裹内容物,其降解产物氨基酸、游离脂肪酸等可供细胞物质能量循环,细胞自噬在肝脏疾病的发生发展中有重要的作用,最近研究表明,细胞自噬可以通过降解脂滴为肝星状细胞的活化提供能量从而促进肝纤维化的发生。     

自噬在肝脏缺血再灌注损伤中的作用及研究进展

肝脏缺血再灌注损伤是肝脏外科常见的一种并发症,是导致术后肝功能障碍的重要原因.肝脏缺血再灌注损伤的发生机制十分复杂,涉及多种因素.自噬是真核细胞内的一种溶酶体依赖的降解途径,具有维持细胞内环境稳定的作用.自噬在肝脏缺血再灌注损伤的发生发展过程中发挥重要的作用,是目前的研究热点之一,但是其具体作用及机制仍有较大争议.本文就自噬在肝脏缺血再灌注损伤中的作用及其机制作一详尽综述.     

自噬在肝脏疾病中的研究进展

自噬(autophagy)是一种进化保守的溶酶体依赖的自身降解途径,是细胞在遇到应激反应等刺激时,将细胞质内多余的蛋白质或损伤的细胞器等物质包绕至自噬体中并与溶酶体结合将其降解的过程.自噬几乎存在于所有真核细胞,不仅参与维持细胞内环境稳定及生长、分化的重要过程,而且是细胞面临饥饿、生长因子匮乏等应激环境的应对策略.自噬在多种生理过程中发挥重要作用,自噬缺陷则与许多疾病的发生密切相关,如肿瘤、神经退行性疾病.自噬在肝脏疾病中的研究日益增多,自噬水平的变化对肝脏生理功能和疾病发生的影响及如何通过调控自噬治疗肝脏疾病成为研究的热点.现对自噬在肝脏中的生理功能及其在几种常见肝脏疾病发生和治疗中的作用做一综述.     

肝脏非实质细胞在肝脏缺血再灌注损伤中的作用

肝脏非实质细胞在肝脏中发挥着非常重要的作用。回顾近几年关于非实质肝细胞,如Kupffer细胞、肝窦内皮细胞、肝星状细胞、树突状细胞等在肝脏缺血再灌注损伤(HIRI)中的作用。分析表明肝脏非实质细胞在HIRI过程中扮演着非常重要的角色,能通过各种途径最终加重或者减轻HIRI。     

自噬在HBV及相关肝脏疾病中的双重作用

自噬是一种溶酶体降解过程,其在疾病的发生发展中具有双重作用,即自噬促进细胞存活,又可诱导细胞死亡。简述了自噬在HBV、慢性乙型肝炎、肝纤维化及肝细胞癌中的双重作用,以及自噬在相关肝脏疾病中的作用机制。提出了细胞自噬可能是未来HBV相关肝病治疗的研究方向,为肝纤维化和肝细胞癌的治疗提供了新思路。     

肝内微环境诱导的自噬在非酒精性脂肪性肝病中的作用

非酒精性脂肪性肝病(NAFLD)是以肝细胞内脂质过度沉积为主要特征的一系列肝脏异常病变，也是全球范围内最常见的慢性肝病。自噬是细胞降解自身成分、参与维持器官功能及机体稳态的一种基本细胞过程，与NAFLD的进展存在密切联系。机体遭受的高脂、缺氧和压力等在肝脏内形成了细胞外微环境的异常改变，这些异常微环境可能通过诱导的肝脏细胞自噬促进NAFLD的发生发展。本文基于肝脏内的多种微环境特征，对肝细胞、Kupffer细胞、肝星状细胞等肝脏细胞的自噬在NAFLD进展中的作用和机制进行综述。     

非选择性自噬在脓毒症心肌病中的研究进展

正自噬是细胞内非常重要的分解代谢过程,其负责细胞内一些大分子、衰老以及损伤细胞器的降解及降解产物的再利用。自噬在维持细胞内环境稳态和应对细胞内外应激等方面发挥重要作用[1]。完整的自噬流包括自噬结构的形成、通过自噬体或者自噬内涵体与溶酶体的融合,将自噬底物运送至溶酶体,发生底物的降解,并将大分子物质释放回细胞质的整个流程。其分为起始、形成和降解3个阶段。自噬的起始主要是Ⅲ型磷脂酰肌醇3-激酶复合体(VPS34-VPS15-Be-     

肝再生增强因子研究进展

肝再生增强因子(augmenter of liver regeneration,ALR)又名肝刺激物质或肝细胞生成素,广泛表达于全身各组织器官,尤其是在肝细胞中.近年来不断有研究证实,ALR具有强大的促进肝脏再生和受损肝脏细胞增殖的功能,在肝细胞移植、重型肝炎的发病、肝脏的再生和肝癌发生发展中发挥重要作用.     

肝窦内皮细胞研究进展

肝窦内皮细胞(sinusoidal endothelial cell,SEC)是数量最多的肝脏非实质细胞,占非实质细胞总数的44％～60％,其形态结构和功能具有异质性。SEC与肝微循环、血脂代谢、内分泌代谢、内环境稳定、肝再生、肝细胞移植和肝癌发生等密切相关。     

肝血窦内皮细胞在肝再生和肝纤维化发生中的作用

肝血窦内皮细胞是肝脏非实质细胞的主要组成细胞,是覆盖于肝窦的薄层扁平状细胞,表面富含窗孔,是肝窦和窦状间隙之间溶质交换的开放通道。肝血窦内皮细胞的分泌功能尤其是Wnt信号通路在维持Axin2+源性肝细胞的自我更新、促进肝部分切除或肝损伤时肝再生中均发挥重要的保护作用。肝损伤时,肝血窦内皮细胞结构发生改变,表现为窗孔消失和内皮下基底膜的形成,即肝窦毛细血管化。肝窦毛细血管化既是肝纤维化发生的前奏,也会促进肝纤维化的进展。肝窦内皮细胞在不同生理或病理状态下可通过信号通路的转换实现肝再生和肝纤维化调控作用的转换。肝血窦内皮细胞参与肝再生和肝纤维化机制的深入认识有望为慢性肝病的防治提供新的治疗靶点。     

青少年高血压的研究进展

随着人们生活和行为方式的改变,高血压发病明显呈年轻化趋势。在青少年时期识别高血压病高危人群有助于早期进行有效干预和治疗,降低未来高血压的发生率及其严重性。现试从青少年高血压的诊断、发病因素、特点、治疗策略等方面的研究进展作一综述。     

Morbidity in cardiovascular diseases in immigrants in Sweden

INTRODUCTION: Although immigration to Sweden has increased in the last few decades, the incidence rates of cardiovascular disease and coronary heart disease in immigrants are unknown. The aim of the present study is to estimate whether place of birth affects the incidence rates of cardiovascular disease and coronary heart disease. MATERIAL AND METHODS: The study was designed as a follow-up study on morbidity in cardiovascular disease and coronary heart disease between 1 January 1997 and 31 December 1998, including three and a half million persons with age range 35-64 years, of whom 550 000 were born abroad, from the database MigMed consisting of the whole Swedish population. Incidence rates and relative risks were estimated by indirect standardization and a proportional hazard model. RESULTS: The age-adjusted risk of coronary heart disease was higher in most foreign-born groups than in Swedes. For example, in nine of 12 male groups, the relative risks varied between 1.1 and 2.2, and in seven of 12 female groups, the relative risks varied between 1.4 and 2.5. When also adjusting for level of education and employment status, the risks were still high, but on a lower level. CONCLUSIONS: Foreign-born people possess an over-risk of cardiovascular or coronary heart disease(CVD/CHD) compared with Swedish-born persons, also when level of education and employment status are taken into account.     

C·肉毒杀鼠素(冻干剂)应用研究

目的为研究C·肉毒杀鼠索对杀灭达乌尔黄鼠(简称黄鼠)的大面积应用情况和对家畜、家禽的毒害作用,进行了C·肉毒杀鼠素的应用研究.方法大面积投毒采用ES-2药饵撒播机[1],间隔约80m进行条投.羊、鸡采用直接灌胃.结果大面积应用的灭鼠率为83.72%.对羊、鸡最高剂量分别为500万MLD、150万MLD,均未出现中毒现象.结论 C·肉毒杀鼠素是较为理想的草原大面积杀灭黄鼠的理想、首选药物.     

高龄老年高血压的临床研究进展

随着社会老龄化进程的加快,80岁以上高龄老人的绝对数量以及占总人口的比例均在增加,如何提高高龄老年高血压的防治水平备受关注。现试从高龄老年高血压的临床特点、治疗策略等方面的临床研究进展作一综述。     

中国老年性耳聋的研究与干预进展

老年性耳聋已成为影响我国老年人生活质量的最主要的慢性病之一。助听器是目前帮助听力损失的老年人克服交流障碍的主要手段。在我国,数字助听器已逐渐取代模拟助听器并且体现出了更好的效果。但是老年听力损失患者中使用助听器的比例仍然很小。人工耳蜗植入也已被应用在老年患者中。我国针对老年人的听力康复服务还有较长的路要走。     

糖尿病大鼠心室肌细胞钾通道的改变

目的研究糖尿病大鼠心室肌细胞钾通道的改变及增加葡萄糖代谢对其的作用。方法取体重150～200g的雄性SpragueDawley大鼠,腹腔注射链脲菌素(STZ)建立糖尿病模型,采用酶解法获得单个心室肌细胞,应用膜片钳全细胞记录技术记录钾电流。结果糖尿病大鼠心室肌细胞瞬间外向性钾流(Ito)密度较对照组显著降低[ 60mV时,分别为(15.90±1.19)pA/pF(n=25)和(28.55±0.97)pA/pF(n=12),P<0.001];分别用100nmol/L胰岛素及1.5mmol/L二氯乙酸在体外预处理心室肌细胞4～5h和3～4h使Ito密度恢复至对照组水平[ 60mV时,分别为(29.40±0.38)pA/pF(n=20)和(27.35±0.97)pA/pF(n=12)]。结论糖尿病大鼠心室肌细胞钾通道功能发生改变,增加葡萄糖代谢可逆转这一改变,提示葡萄糖代谢与Ito功能间存在一定关系。     

Sex Differences in Ethanol-induced Dopamine Release in Nucleus Accumbens and in Ethanol Consumption in Rats

In vivo microdialysis was used to examine changes in nucleus accumbens and striatal dopamine, dihydrophenylacetic acid (DO-PAC), and homovanillic acid (HVA) following acute administration of ethanol (0.0, 0.25, 0.5, 1.0, or 2.0 g/kg) in male and female Long-Evans rats. Following dialysis, rats were trained to bar-press for oral ethanol reinforcement. In nucleus accumbens, females showed significant increases in extracellular dopamine following 0.25 or 0.5 g/ kg ethanol, but did not show significant increases over baseline at the higher doses. Males showed slight increases in dopamine at the lower doses and decreased dopamine at 2.0 g/kg. In striatum, both sexes showed increased dopamine at the lower doses and decreased dopamine at 2.0 g/kg. There were slight increases in nucleus accumbens DOPAC and HVA at some doses in both sexes, but no changes in striatal metabolite levels. In addition to showing increased responsiveness to ethanol-induced mesolimbic dopamine stimulation, females consumed more ethanol than males during behavioral testing. The pattern of both greater ethanol-induced nucleus accumbens dopamine release and greater ethanol consumption in females supports the hypothesis that ethanol reward is mediated, at least in part, by the mesolimbic dopamine system.     

Dead in Bed Syndrome in Young Diabetic Patients in Norway

The incidence of unexplained deaths (‘dead in bed syndrome’) in Norwegian diabetic patients under the age of 40 was investigated during the period 1981–1990. During this 10-year period there were 240 deaths of all causes in the age group 0–39 years. Sixteen of these cases fulfilled the following criteria of the ‘dead in bed syndrome’: (1) patient found dead in an undisturbed bed; (2) patient observed to be in good health condition the day before; (3) no clinical evidence of late complications (except background retinopathy in two cases). Of the 16 cases ascertained, 10 were males and 6 females. The age range was 7–35 years, and the duration of diabetes varied between a few months and 26 years. Autopsy, performed in 13 cases, did not reveal any cause of death. Nine patients had been using insulin regimens with multiple daily doses. Twelve patients were reported as having had frequent episodes of hypoglycaemia, with nocturnal episodes in 10 cases. There was apparently an increasing incidence of unexplained deaths during the study period, with 12 of 16 cases occurring in the years 1988 to 1990.