肾纤维化手术动物模型构建及相关机制研究进展

慢性肾疾病发展到一定阶段可引起肾纤维化。肾纤维化可由多种因素诱导产生,包括肾受到严重创伤和感染,肾血液循环阻塞或者免疫反应等。各种因素引起肾组织受损后,大量胶原纤维在间质沉积,瘢痕形成,导致肾结构和功能发生改变,从而引起肾纤维化。迄今关于肾纤维化的发生机制尚不完全明确,而理想的肾纤维化模型对于肾纤维化的机制研究具有重要意义。目前很多关于肾纤维化的研究是通过手术的方式建立肾纤维化的动物模型。因此本文主要总结了近年来关于肾纤维化手术模型的构建方法及肾纤维化的发病机制。     

Hepatitis B virus directly promotes collagen I expression of LX-2 cells without infection in vitro

Aim: To investigate direct effects of hepatitis B virus (HBV) on collagen type I in vitro. Methods: Collagen type I were measured after LX‐2 cell cultured with purified or serum HBV for 12, 24 and 48 h. Furthermore, evidence of HBV infection to LX‐2 were detected, and different inhibitors were used to identify pathways regulating collagen I expression. Results: The 3 × 10⁵ IU/mL purified/serum HBV increased collagen type I mRNA expression by 2.2‐/3.2‐ and 1.3‐/1.5‐fold at 24 and 48 h, respectively. Collagen type I protein in the supernatant of purified/serum HBV group also increased compared to the control group (408.0 ± 8.0/384.4 ± 6.8 vs 262.7 ± 15.7 ng/mL, P < 0.05). However, the 3 × 10⁷ IU/mL purified/serum HBV increased collagen type I expression similar to that of 3 × 10⁵ IU/mL, while 3 × 10³ IU/mL group showed no effect. Human HBV immunoglobulin alleviated HBV‐induced collagen I expression, but no evidence of HBV infection was found. Neutralization of transforming growth factor beta, tumor necrosis factor alpha, platelet‐derived growth factor, extracellular signal‐regulated kinase and TGF‐β receptor had no obvious inhibitory effects; only inhibition of p38 mitogen‐activated protein kinase decreased collagen type I mRNA expression by 0.5‐/0.4‐ and 0.4‐/0.3‐fold at 24 and 48 h, respectively. It reduced collagen type I protein in the purified/serum HBV group for 48 h (252.1 ± 14.1/251.7 ± 18.8 vs 403.9 ± 4.9/385.0 ± 4.2 ng/mL, P < 0.05). Conclusion: HBV directly promotes collagen type I expression of LX‐2 cells without infection in vitro.     

慢支、肺气肿并肺动脉高压的特征及其机制探讨

目的:探讨慢性阻塞性肺疾病(COPD)肺动脉高压的不同阶段的特征及其相关机制.方法:将40只Wistar大鼠随机分成5组,每组8只.A组:低氧性肺动脉高压组,10%低氧,8 h/d,2周;B组:慢支、肺气肿并肺动脉高压组,分别于第1天、第14天经气管注入脂多糖(LPS)200 μg,烟熏2 h/d,6周,最后2周同时叠加18%低氧,8 h/d;C组:慢支、肺气肿组,分别于第1天、第14天经气管注入LPS 200 μg,烟熏2 h/d,共6周;D组:18%低氧,8 h/d,2周;E组:正常对照组,正常饲养6周.各组作血气分析,肺血流动力学测定和肺泡灌洗液(BALF)白细胞总数及分类计数.观测气道及肺组织和肺血管的病理组织学改变.结果:①与E组比较A、B组PaO2呈不同程度降低(P＜0.05),A、B组右心室收缩压(RVSP)、平均肺动脉压(mPAP)、右心室与左心室 室间隔重量比(RV/LV S)升高(P＜0.05).A、B组肌化型动脉(MA)增多,管壁增厚(P ＜0.05);②C、D组血气分析无变化(P＞0.05),与E组比较,C组RVSP、mPAP、RV/LV S升高(P＜0.05),C组MA增多(P＜0.05),但管壁无增厚(P＞0.05);D组肺血流动力学、肺血管重塑指标无改变(P＞0.05);③支气管肺泡灌洗液(BLAF)中,A、D组白细胞总数及分类计数与E组相当(P＞0.05),病理主要以上皮细胞变性坏死、黏液杯状细胞增生为主,炎细胞浸润不明显(P＞0.05).B、C组白细胞总数及分类计数增多(P＜0.05),中性粒细胞比例增多(P＜0.05),气道病理符合慢支、肺气肿改变,管壁呈现以淋巴细胞为主的多种炎细胞浸润.结论:COPD肺动脉高压在无低氧时期已经形成,炎症因素起重要作用,早期肺血管重塑以MA比例增高为主要表现,低氧加剧了病情的发展,并出现MA肌层的增厚,管腔变小.     

Probing protein dissociation from gold nanoparticles and the influence of temperature from the protein corona formation mechanism

Gold nanoparticles (AuNPs) provide a novel approach for protein enrichment and analysis due to their protein adsorption properties, forming a so called protein corona. This corona can significantly influence the protein''s structure and characteristics, hindering their identification in situ. Dissociation is an important solution to analyze and identify the composition of protein coronas. However, a comprehensive picture of adsorbed protein dissociation is lacking. In this study, the protein dissociation from the protein corona and influencing factors were investigated on the basis of the formation mechanism and time evolution. Temperature and cysteine are the key factors influencing protein dissociation by altering the protein''s binding ability. The results showed that half Au–S formation time is an important time point for thio-protein dissociation by the method of high speed centrifugation. When incubated for longer than that time, the thio-protein located in the hard corona could only be separated by β-mercaptoethanol replacement under analytical ultracentrifugation. However, Fourier-transform infrared spectroscopy (FTIR) revealed significant changes that occurred in βlg''s secondary structure after ultracentrifugation. The Au–S bond formation time offers the potential to define the protein enrichment time of AuNPs.

A protein corona changes protein''s structure and characteristics, hindering their identification in situ. Dissociation is an important solution to identify their composition.     

One‐Step Approach for the Preparation of Organic‐Inorganic Janus‐Like Particles by Alkalization of Polystyrene‐block‐Poly(2‐vinylpyridine)/FeCl3 Complex Micelles

A novel approach to organic‐inorganic Janus‐like particles based on the alkalization process of polystyrene‐block‐poly(2‐vinylpyridine) (PS‐b‐P2VP) micelles containing FeCl₃ precursors in the P2VP cores in toluene is presented. It is found that by addition of a small amount of NaOH solution to a solution of the spherical PS‐b‐P2VP/FeCl₃ micelles, organic‐inorganic Janus‐like particles with a produced α‐FeOOH domain on one side and PS‐b‐P2VP block copolymers on the other can be prepared. The Janus‐like nanoparticles obtained by this facile approach may have potential application in biomedical areas.     

应用寡核苷酸圈套技术研究胰岛素调控人α1(Ⅰ)型胶原基因转录

目的应用寡核苷酸圈套技术研究胰岛素对人COL1A1基因转录的调控。方法建立稳定转染pCOLH12.5质粒(含CAT基因与人COL1A1基因-2483～ 42bp片段)的WI-38细胞株,加入不同剂量胰岛素,测CAT值;分别瞬时转染不同序列ssPT入克隆细胞株中,加入2.5μmol/ml的胰岛素,测CAT值。结果2.5μmol/ml的胰岛素显著增加了COL1A1基因启动子活性;含sp1位点的ssPT浓度为120 nmol/L时,受胰岛素刺激所增加的CAT值得到显著抑制,不含sp1位点的ssPT无此作用。结论ssPT能够应用于基因转录调控的研究。胰岛素在人COL1A1基因上的反应元件可能位于启动子-129至-105区域内。     

喉科擒拿法概述

目的:发掘整理喉科绝技擒拿法的相关资料,探讨该法在当代临床的应用前景。方法:通过搜集文献资料中有关喉科擒拿法的内容,特别是中医五官科奠基人干祖望教授的"擎拿"技艺,探讨喉科擒拿法的基本操作手法及其分类,以及练功注意事项。结果:喉科擒拿法是中医喉科的一门绝技,不仅在急救时有奇效,在治疗咽喉急性肿痛时也大有用武之地,操作简便,见效快。结论:喉科擒拿法具有浓郁的中医传统特色,是一门濒临失传的中医五官科绝技,值得发掘推广。     

海军飞行员代谢性疾病患病情况及其影响因素调查

 目的 调查海军飞行员高血压、高血糖、血脂异常的患病情况及其影响因素.方法 对随机抽取的海军飞行员查体资料进行分析,获取飞行员年龄、身高、体重、飞行机种、吸烟、饮酒情况及血压、空腹血糖、血脂水平,进行统计学处理.结果 380名飞行员中,血压异常33人,占8.7%;血脂异常103人,占27.2%;空腹血糖异常13人,占3.3%;BMI异常186人,占48.9%.血压、血糖、血脂异常与飞行机种无关,与年龄、体重指数、吸烟、饮酒等因素相关.结论 超重、吸烟、饮酒影响飞行员血压、血脂及血糖水平,应采取有效的预防措施,以降低高血压、糖尿病及血脂异常的发病危险,延长飞行寿命.     

乳香提取物对HL-60细胞株VEGF分泌及其Flt-1受体表达的影响

目的:探索不同浓度乳香提取物作用于HL-60细胞后,白血病细胞株HL-60细胞VEGF mRNA表达及VEGF蛋白分泌及受体Flt-1的变化.方法:MTT法检测乳香提取物对细胞增殖的抑制作用,选择适当的药物浓度及作用时间:RT-PCR法检测乳香提取物处理前后HL-60细胞中VEGF mRNA表达水平;Western B...     

B超引导下经皮穿刺注射四环素与无水乙醇治疗肾囊肿疗效比较

目的:观察比较B超引导下经皮穿刺注射四环素与无水乙醇治疗肾囊肿的疗效。方法:92例单纯性肾囊肿在B超引导下经皮穿刺抽液后,注入硬化剂,45例注射四环素(1组),47例注射无水乙醇(2组)。1个月和3个月复查B超并比较两组疗效及并发症。结果:四环素与无水乙醇在治疗肾囊肿疗效方面无明显差异,而在副反应与并发症方面,四环素组发生率明显低于无水乙醇组。结论:超声引导下经皮穿刺注射硬化剂治疗肾囊肿方法简便,疗效确切;四环素治疗肾囊肿具有和无水乙醇相似的疗效,且更为安全。