特发性肺间质纤维化与肺肌成纤维细胞

特发性肺纤维化(idiopathic pulmonary fibrosis，IPF)是一种病因不明、发病机制不清、缺乏治疗手段的致命性弥漫性肺间质疾病，其病理特征是肺泡上皮损伤、成纤维细胞灶(fihrohlast foci)的形成以及细胞外基质的过度沉积，最终导致了肺组织结构的异常重塑。近年来的研究发现成纤维细胞灶主要由表达α-平滑肌肌动蛋白(α—smooth muscle actin，α-SMA)的肌成纤维细胞构成，是造成细胞外基质异常沉积的主要细胞。大量成纤维细胞灶的出现可提示纤维化处于进行性活动期，可作为IPF进入不可逆纤维化过程的一个组织病理上的指标。     

矽肺病人的心理问题及护理对策

矽肺是在职业活动中长期吸入大量游离二氧化硅粉尘所引起的以肺组织弥漫性纤维化为主的全身性疾病。矽肺患者主要表现为胸闷、气短或胸痛、咳嗽、体力减弱，常并发肺结核、肺部感染。该病是尘肺中最常见，进展最快，危害最严重的一种类型。由于此病无法逆转且病程长，反复感染，逐年加重，使患者产生各种心理问题，生活质量下降。针对这一问题，我们采用了相应的护理对策，为患者提供了一个良好的心理环境，提高了患者的适应能力和生存质量。我们对36例住院矽肺患者进行了观察和护理，现将体会总结如下。     

促进儿童坚持用药

在了解及处理坚持用药的情况较差时，医生往往遇到很多困难。困扰医生的一个主要问题是，如何护理患有急性或危及生命的疾病而不能长期坚持治疗的儿童。对医生来说，更难的是如何了解父母何时不能为子女提供适当的护理。近30％～70％的患慢性疾病者，因为治疗时间长、服用的药物种类多及症状时有缓解而不能坚持用药。临床经验表明，患有慢性疾病，如囊性纤维化、癫痫、哮喘、糖尿病患者坚持用药的情况较差。     

AST-120对CKD进程的影响

从1991年开始，口服的碳吸附剂AST-120在日本被用于治疗慢性肾脏病（CKD）患者，但是在其他国家却不常用。在CKD的动物模型中，AST-120可清除尿毒症毒素，减轻氧化应激；在组织学水平观察到它可明显延缓肾小球硬化、肾间质纤维化、近端肾小管肥大的进展。在部分肾切除的大鼠模型中，AST-120显示出对其肾脏的保护作用超过了低蛋白饮食和降压药物。在CKD的患者中，AST-120也显示可延缓肾小球滤过率（GFR）及血肌酐浓度倒数下降的作用。     

血管内皮生长因子及其受体在单侧输尿管梗阻大鼠术侧肾脏的表达

血管内皮生长因子（VEGF）的主要作用是刺激血管内皮细胞的增殖与分化、抑制内皮细胞凋亡，主要通过两个受体Flk-1和Flt-1发挥作用。本研究旨在明确VEGF及其受体在单侧输尿管梗阻（UUO）大鼠术侧肾脏不同时间的表达变化情况，为进一步探讨其在UUO大鼠小管间质纤维化中的作用机制提供实验依据。     

百令胶囊对大鼠肾小管间质纤维化的防治作用

目的：观察百令胶囊对肾小管间质纤维化的防治作用及其作用机制。方法：雄性SD大鼠90只,随机分为对照组（30只）、模型组（30只）、预防组（30只）。以2%腺嘌呤淀粉混悬液150mg.kg^-1.d^-1灌胃,连续17周,制作大鼠肾小管间质纤维化模型;预防组加以1.5g.kg^-1.d^-1百令胶囊溶于生理盐水灌胃以预防肾小管间质纤维化;对照组以等体积的2%淀粉溶液和生理盐水灌胃。分别于实验第7周、12周、17周时随机处死10只大鼠,进行血肌酐（Scr）、尿素氮（BUN）,24h尿蛋白定量和尿NAG酶检测,光镜下观察肾组织的病理变化,计算肾小管间质纤维化指数;免疫组织化学法检测肾脏HGF、TGF-β1的表达情况。结果：（1）功能学变化：与对照组比较,各时相点模型组、预防组大鼠尿蛋白、尿NAG酶、Scr及BUN均升高（P〈0.01）,但预防组低于模型组（P〈0.01）;模型组、预防组自身对照各指标均较前一时相点升高（P〈0.01）。（2）病理学变化：7周时模型组、预防组即有肾小管间质损害;模型组、预防组自身对照肾小管间质损害均较前一时相点加重（P〈0.01）,但7周、12周时预防组肾小管间质损害均较模型组为轻（P〈0.01）,17周时两组间无统计学差异（P〉0.05）。（3）免疫组化：模型组、预防组大鼠肾脏HGF表达7周、12周时高于对照组大鼠（P〈0.01）,17周时低于对照组（P〈0.01）,且各时相点预防组均高于模型组（P〈0.01）;模型组、预防组自身对照均较前一时相点降低（P〈0.01）,17周时表达量最低。各时相点模型组、预防组大鼠肾脏TGF-β1的表达均高于对照组（P〈0.01）,且预防组均低于模型组（P〈0.01）,模型组、预防组自身对照均较前一时相点升高（P〈0.01）,17周时表达量最高。（4）HGF表达量与TGF-β1表达量呈负相关（r=-0.999,P〈0.01）。结论：百令胶囊对早期肾小管间质纤维化有一定的防治?     

低蛋白饮食对环孢素A肾病大鼠肾间质纤维化的作用

Objective To investigate whether low-protein diet has protective effect on the progression of renal interstitial fibrosis in rats with cyclosporine A (CsA)-induced nephropathy. Methods Eighteen male Sprague-Dawley rats were randomly divided into three groups (6 rats in each group). The rats in control group (C group) received common diet; in model group (M group) low-salt diet; in intervention group (Ⅰ group) low-salt and low-protein diet. After diet adaptation period of one week, the rats in C group received subcutaneous injection of olive oil 1 mg/kg daily for 5 weeks, while M group and Ⅰ group subcutaneous injection of CsA (diluted into 25 g/L with olive oil) 1 ml/kg for 5 weeks. All the rats were sacrificed at the end of the 5th week. The food-intake and body weight were measured daily. The creatinine clearance (Ccr) was examined before rats were sacrificed. The semi-quantitative pathological analysis on kidney sections was performed. The mRNA and protein expression of transforming growth factor-β1 (TGF-βI) and type Ⅰ collagen (Col Ⅰ) in kidney tissue was determined with real time PCR and immunohistochemical staining, respectively. Results The food-intake and body weight of rats in M and I groups were significantly lower than those in C group (P<0.05). Compared with C group, the Ccr levels in M and Ⅰ groups were significantly reduced [(0.65±0.15) ml/min, (0.40+0.13) ml/min vs (1.55±0.29) ml/min, P<0.05], the relative fibrosis areas of kidney interstitium in M and I groups were significantly increased (3.60%±0.46%, 3.26%±0.75% vs 0.44%±0.24%, P<0.05), the mRNA and protein expression of TGF-β1 in M and I group was significantly up-regulated (by 2.6 and 3.1 times in mRNA and by 1.5 and 1.6 times in protein, respectively, P<0.05), and the mRNA and protein expression of Col Ⅰ in M and I groups was also significantly up-regulated (by 3.0 and 3.5 times in mRNA and by 2.3 and 2.1 times in protein, respectively, P<0.05). There were no significant differences between M and I groups in every parameters above-mentioned except the rat body weight and Ccr. Both the body weight and Ccr in Ⅰ group were significantly lower than those in M group (P<0.05). Compared with C group, the urine osmotic pressure in M group and in I group were deceased (for M group, P>0.05; for I group, P<0.05). Compared with C group, the serum cholesterol levels in M and I groups were significantly increased (P<0.05), and the serum phosphorus level in I group was significantly decreased (P<0.05). The levels of serum albumin and serum calcium of all three groups had no statistical differences (P>0.05). Conclusion Low-protein diet has no renoprutective effects on the rat model of cyclosporin A nephropathy, on the contrary, may induce body weight loss.     

补肾排毒合剂对单侧输尿管梗阻大鼠肾间质MMP-9与TIMP-1基因表达的影响

目的：研究单侧输尿管梗阻（unilateral ureteral obstruction，UUO）后大鼠肾间质MMP-9、TIMP-1基因的表达变化，探讨补肾排毒合剂对肾间质纤维化的保护作用。方法：采用UUO诱导肾间质纤维化的动物模型，将大鼠随机分为假手术组（Sham组）、模型组（UUO组）和补肾排毒合剂治疗组（REM组），用RT—PCR技术检测肾组织在术后3、10、20、30d MMP-9、TIMP-1的基因表达。结果：UUO组TIMP-1 mRNA的表达明显高于Sham组（P〈0．01），REM组TIMP-1 mRNA表达均明显低于UUO组（P〈0、01）。MMP-9 mRNA在UUO术后明显升高，第10天达到高峰，继之下降。REM组10d后下降幅度较小，在20、30d时间点高于UUO组（P〈0，01）。结论：补肾排毒合剂影响MMP-9／TIMP-1的基因表达，从而促进了ECM的降解过程，延缓肾间质纤维化的进展。     

枳棋子对肝纤维化大鼠脂质过氧化的动态影响

将96只肝纤维化模型大鼠随机分为三组。自然恢复组口服羧甲基纤维素钠（CMC—Na）溶液；对照组口服秋水仙碱-CMC—Na混悬液；治疗组口服枳棋子-CMC—Na混悬液，用药后于不同时间点观察各组肝细胞结构变化及纤维化程度，检测肝脏内丙二醛（MDA）和超氧化物歧化酶（SOD）水平。结果与自然恢复组相比，治疗组细胞结构趋于正常，无炎性细胞浸润及气球样变；胶原纤维增生呈局限性，肝组织恢复良好；MDA含量明显降低，SOD活性明显升高。证实枳棋子能明显加速肝脏修复速度，减轻肝纤维化程度，降低脂质过氧化对肝组织的损伤，加快肝组织恢复。