川芎嗪对马兜铃酸肾病大鼠肾间质微血管病变的干预研究

目的探讨川芎嗪对马兜铃酸肾病大鼠肾损害及肾间质微血管病变管周毛细血管（PTC）密度及血管内皮生长因子（VEGF）的变化。方法雄性Wistar大鼠98只分为4组，即模型组、川芎嗪组、苯那普利组各26只，按马兜铃酸（AA）20mg·kg^-1·d^-1灌胃关木通浸膏；对照组20只灌胃饮用水。2h后分组给药：对照组及模型组灌胃饮用水，川芎嗪50mg·kg^-1·d^-1；苯那普利1．8mg·kg^-1·d^-1。分别于4、8、12w末分别处死动物各6只，检测肾功能，肾脏病理，免疫组化观察FTC密度及VEGF表达。结果12w时模型组的血肌酐／体重水平明显升高（P〈0．01），病理表现为弥漫性小管间质损害和灶性纤维化；模型组4w后出现中、重度肾血管病变，FTC密度明显下降；肾小管VEGF表达水平早期代偿性增高，以后逐渐降低并与FTC密度下降一致。川芎嗪组、苯那普利组的肾功能及小管间质病变程度较模型组降低（P〈0．01）；血管病变程度轻，FTC密度明显高于模型组，VEGF表达水平低于模型组。结论马兜铃酸可引起大鼠肾功能减退和肾小管间质损害，使肾间质微血管发生缺血性病变，川芎嗪可改善上述病变程度，并与调节VEGF表达有关。     

关木通浸膏加低盐饮食建立大鼠慢性马兜铃酸肾病模型

目的:探讨用关木通浸膏加低盐饮食建立大鼠慢性马兜铃酸肾病动物模型的方法.方法:制备关木通浸膏剂,并测定其中马兜铃酸(AA)含量.实验分为正常对照组、低剂量组(AA 5 mg·kg-1·d-1)、中剂量组(AA10 mg·kg-1·d-1)、高剂量组(AA 20 mg·kg-1·d-1).给药前一次性腹腔注射速尿4 mg/kg,然后分别灌胃不同浓度的关木通浸膏,给药组给予低盐饮食(钠含量＜0.05%);对照组灌胃同体积自来水.连续给药1周,停药1周,隔周给药.各组每周测量体重,每2周代谢笼法留取24 h尿液;每组分别于第10 d、30 d处死大鼠各2只,第56 d处死其余大鼠,腹主动脉采血,测定相关肾功能指标;取肾组织进行形态学检查.结果:AA用药组尿量均明显增多,体重明显降低,尿蛋白、尿酶排泄量、肌酐等均升高.肾脏病理出现明显的小管间质损伤和典型的早期间质纤维化表现.结论:表明成功建立了大鼠慢性AAN模型,且本方法造价低廉,造模时间短,成功率高.     

不同剂量寻骨风致大鼠慢性肾间质纤维化初探

目的:观察马兜铃科中药寻骨风水煎剂引起大鼠慢性肾间质纤维化与剂量的关系并探讨其发病机制。方法:将雌性Wister大鼠随机分5组:(1)正常对照组(NC组,n=8):给予蒸馏水2 ml/d灌胃;(2)马兜铃酸对照组(AA组,n=16):给予马兜铃酸制剂5 mg.kg-1.d-1腹腔注射;(3)寻骨风高剂量组(XGFH组,n=16):给予寻骨风水煎液27 g.kg-1.d-1灌胃;(4)寻骨风中剂量组(XGFM组,n=16):给予寻骨风水煎液13.5 g.kg-1.d-1灌胃;(5)寻骨风低剂量组(XGFL组,n=16):给予寻骨风水煎液2.7 g.kg-1.d-1灌胃。各组在45 d、90 d时分别处死8只大鼠,处死前测体重、采血、留尿,做肾功能,尿潜血、MA/Cr、TF/Cr及尿NAG/Cr检查,处死后测肾重,留取肾组织行HE、PAS染色,做LN、FN、TGF-β1、MMP-2、TIMP-2免疫组化检查。结果:90 d后AA组、XGFH组、XGFM组大鼠体重和肾重较NC组均有下降(P<0.01或P<0.05),AA组、XGFH组、XGFM组MA/Cr、TF/Cr、NAG/Cr、Scr和BUN明显高于NC组(P<0.05或P<0.01)。光镜检查XGFH组用药45 d后,出现肾小管上皮细胞肿胀,管腔缩小,小管间质增生;AA组、XGFM组肾小管上皮细胞发生空泡变性;XGFH组用药90 d后,肾小管上皮细胞坏死,肾小管萎缩,肾间质出现灶性纤维化。AA组、XGFM组肾脏近曲小管上皮细胞明显肿胀,管腔变小,小管间质增生,部分发生纤维化;XGFL组肾组织未见明显损害。免疫组化显示AA组、XGFH组、XGFM组肾小管和间质上MMP-2的表达下调,而TGF-β1、TIMP-2、LN、FN的阳性表达较NC组明显上调(P<0.05)。结论:XGFH组、XGFM组和AA组均导致了实验大鼠肾小管间质的损害,而且病变的程度与用药剂量相关,XGFH组肾小管间质损害程度最严重,90 d内造成了大鼠肾间质纤维化,同时我们证实了慢性马兜铃酸肾病大鼠肾间质纤维化的发生同致纤维化因子TGF-β1和抑制细胞外基质降解因子TIMP-2的过度表达导致FN、LN胶原纤维在肾间质的过度增殖有关。     

慢性马兜铃酸肾病大鼠肾组织微血管损伤机制及温阳活血方的干预作用

目的:研究慢性马兜铃酸肾病大鼠肾组织微血管损伤机制及温阳活血方对其干预作用,探讨温阳活血方对慢性马兜铃酸肾病的保护作用机制.方法:将48只雄性SD大鼠随机分为5组.(1)正常对照组(n=8):予生理盐水灌胃;(2)模型组(n=10):按关木通水煎液10 ml·kg-1·d-1(相当于关木通40 g·kg-1·d-1,马兜铃酸A 2.6 mg·kg-1·d-1)给大鼠灌胃;(3)中药组(n=10):在模型组基础上,再予温阳活血方30 g·kg-1·d-1灌胃;(4)西药组(n=10):在模型组基础上,再予科素亚33.3 mg·kg-1·d-1灌胃;(5)中西药结合组(n=10):在模型组基础上,再予温阳活血方30 g·kg-1·d-1 科素亚33.3 mg·kg-1·d-1灌胃.20周末,光镜观察肾脏病理,采用CD 34免疫组化染色来反映肾组织微血管的损伤情况,实时PCR检测肾组织中Ang-1、Ang-2、Tie-2和VEGF mRNA的表达.结果:(1)与正常对照组比较,模型组大鼠肾组织CD34表达明显降低(P＜0.01);而治疗组大鼠肾组织CD34表达较模型组明显升高(P＜0.05),其中尤以中药组明显(P＜0.01);(2)与正常对照组比较,模型组大鼠肾组织Ang-1、Tie-2、VEGF mRNA表达明显降低(P＜0.05,P＜0.01),Ang-2表达明显升高(P＜0.01);而治疗组大鼠肾组织Ang-1、Tie-2、VEGF mRNA表达较模型组明显升高(P＜0.05,P＜0.01),中西药结合组Ang-2表达明显减少(P＜0.01).结论:慢性马兜铃酸肾病大鼠肾组织存在微血管的损伤,其损伤机制可能与Ang-1、Tie-2和VEGF mRNA的下调,Ang-2 mRNA上调有关,温阳活血方能明显改善微血管的损伤,对慢性马兜铃酸肾病大鼠肾脏具有保护作用.     

苯那普利和缬沙坦联合应用对肾病大鼠肾脏细胞周期调控的影响

目的：探讨苯那普利和缬沙坦联合应用对肾硬化大鼠肾脏细胞周期调控的影响。方法：55只SD大鼠分为5组,即对照组、模型组、苯那普利组、缬沙坦组及联合组。对模型组和三治疗组大鼠行单侧肾脏切除,1周后给予阿霉素（5mg/kg）尾静脉注射,建立肾小球硬化模型。自注射阿霉素后,苯那普利组和缬沙坦组分别给予苯那普利6mg.kg-1.d-1、缬沙坦20mg.kg-1.d-1灌胃,联合组给予苯那普利3mg.kg-1.d-1联合缬沙坦10mg.kg-1.d-1灌胃。12周后全部处死,检测肾脏周期素D1和P27的表达,计算阳性细胞所占的百分数。结果：周期素D1在苯那普利、缬沙坦、联合组较模型组明显减少（P均〈0.01）,而联合组与苯那普利、缬沙坦组之间无差异。P27在苯那普利、缬沙坦、联合组较模型组明显增高（P均〈0.01）,而联合组又高于苯那普利、缬沙坦两组（P均〈0.05）。P27与周期素D1均呈负相关。结论：苯那普利和缬沙坦均通过减少肾脏周期素D1和增加P27的表达延缓肾小球硬化,联合应用苯那普利和缬沙坦对P27的调控比单独应用作用更大。     

川芎嗪、泼尼松和贝那普利对马兜铃酸致大鼠急性肾小管坏死的干预作用比较

目的 建立关木通所含马兜铃酸(AA)致大鼠急性肾小管坏死(ATN)实验动物模型，并观察和比较川芎嗪、泼尼松和贝那普利对大鼠肾小管的保护作用。方法 将雄性SD大鼠随机分为6组，每组12只。正常组予蒸馏水3 ml/d灌胃；模型组、泼尼松组、贝那普利组、川芎嗪Ⅰ组和川芎嗪Ⅱ组均先予关木通水煎剂(含生药2 g/ml、AA 0.54 mg/ml、AA-Ⅰ 0.46 mg/ml)5 g&#8226;kg-1&#8226;d-1 灌胃 60 d，再予10 g&#8226;kg-1&#8226;d-1 灌胃30 d。灌关木通2 h后，正常组与模型组予生理盐水灌胃，其余4组分别予泼尼松5 mg&#8226;kg-1&#8226;d-1、贝那普利1.7 mg&#8226;kg-1&#8226;d-1、川芎嗪50 mg&#8226;kg-1&#8226;d-1和川芎嗪150 mg&#8226;kg-1&#8226;d-1 灌胃。于90 d后进行肾组织病理检查。 结果 正常组为正常肾组织。模型组光镜可见近曲肾小管上皮细胞成片状空泡变性，刷状缘紊乱、消失，管腔内可见脱落的上皮细胞，肾小管基膜(TBM)裸露、部分断裂、个别增厚及萎缩；肾间质轻度水肿、多灶性炎细胞浸润；肾小球系膜细胞局灶节段性轻、中度增生和系膜基质轻度增多；部分小叶间动脉管壁增厚。其余4组与模型组比较，病变均明显减轻，表现为近曲肾小管上皮细胞空泡变性明显减少，少部分刷状缘紊乱、消失，个别管腔内可见脱落的上皮细胞，个别TBM断裂及增厚减轻；肾间质炎细胞减少或消失。模型组电镜可见近曲小管上皮细胞空泡变性和脂肪变性，线粒体肿胀，细胞器减少，细胞核碎裂，细胞凋亡；间质中可见炎细胞浸润(吞噬细胞与淋巴细胞)和淋巴细胞浸入到上皮细胞中；小叶间动脉管壁增厚、管腔狭窄。 其余4组与模型组比较，近曲小管上皮细胞轻度空泡变性、个别线粒体肿胀，个别细胞核轻度固缩、大部分正常；间质中可见少量吞噬细胞和淋巴细胞。其中以川芎嗪Ⅱ组和泼尼松组病变减轻尤为显著。 结论 (1)模型组光镜和电镜结果主要表现为ATN，表明成功建立了大鼠ATN实验动物模型；(2)川芎嗪、泼尼松和贝那普利对AA致大鼠ATN均具有保护作用，且以川芎嗪和泼尼松的药效尤为明显。     

甘草酸对大鼠慢性马兜铃酸肾损害的保护作用及其机制研究

目的：探讨甘草酸对马兜铃酸肾病（AAN）大鼠肾损害及纤维化的保护作用及其机制。方法：雄性Wistar大鼠98只随机分为4组：对照组20只灌胃等体积饮用水，模型组、甘草酸组、泼尼松组每组26只，均按马兜铃酸（AA）20mg·kg^-1·d^-1灌胃关木通浸膏；2h后治疗组给予：甘草酸25mg·kg^-l·d^-1，泼尼松3.15mg·kg^-l·d^-1，对照组、模型组灌胃饮用水。分别于第4、8、12周处死动物，取肾组织行HE、PAS、Masson染色，病理学观察分析肾小管损伤和间质纤维化程度，免疫组化分析PCNA、VEGF、TGF-βl蛋白表达。结果：模型组肾小管损伤分值增高，纤维化程度严重，治疗组肾小管损害和纤维化程度均减轻（甘草酸组15，94％、泼尼松组12，49％）。模型组4周时PCNA、TGF-β1、VEGF水平显著升高，随着时间延长PCNA、VEGF表达逐渐下降，TGF-βl则呈持续阳性高表达；治疗组同期PCNA阳性表达水平较模型组高，VEGF、TGF-β1表达水平较模型组下降。结论：甘草酸对关木通致大鼠马兜铃酸肾损害和纤维化有一定保护作用，其机制可能与提高肾小管上皮的损伤修复能力，调节VEGF、TGF-β1的蛋白表达水平有关。     

肾性贫血动物模型的制作

目的:应用适量马兜铃酸(aristolochic acid,AA)探索创建肾性贫血小鼠模型。方法:6周龄雄性C57BL/6小鼠分3组,正常对照组;马兜铃酸腹腔注射组:AA/2d组(马兜铃酸3 mg·kg^-1·2 d^-1)和AA/3d组(3 mg·kg^-1·3 d^-1),共给药6周。造模第6、9、12周观察肾功能、贫血指标、肾脏病理评分、肾纤维化及肾组织EPO的蛋白表达情况。结果:给药6周时,血肌酐AA/2d组(29.9±1.5)μmol/L和AA/3d组(31.0±1.9)μmol/L均明显高于对照组(8.7±1.4)μmol/L,P<0.001;Hb水平AA/2d组(88.3±3.1)g/L、AA/3d组(85.7±7.4)g/L都明显低于对照组(148.7±4.9)g/L,P<0.001;HCT值AA/2d组、AA/3d组分别为0.30±0.01、0.29±0.02还是都明显低于对照组(0.51±0.02),P<0.001;肾脏病理呈现明显的肾间质纤维化,肾组织中EPO蛋白表达水平下降,提示肾性贫血模型成功。连续观察9、12周,上述变化持续存在,但AA/2d、AA/3d组间的临床病理指标无统计学意义。结论:3 mg·kg^-1·3 d^-1马兜铃酸连续给药6周可成功建立合格稳定的肾性贫血小鼠模型,该模型临床表现为不可逆的肾衰竭和贫血,肾组织中的促红素表达下降,肾脏病理表现为慢性肾间质纤维化。     

益肾胶囊对糖尿病肾病模型肾小球足细胞的影响

目的：观察益肾胶囊对糖尿病肾病（DN）大鼠肾组织病理改变及足细胞超微结构的影响。方法：将60只Wis-tar大鼠随机分为4组：正常对照组（对照组）、DN模型组（模型组）、苯那普利组、益肾胶囊组。于注射链脲佐菌素（STZ）后3d起,苯那普利组每日每只灌胃苯那普利3.125mg.kg-1.d-1,益肾胶囊组每日每只灌胃益肾胶囊625mg.kg-1.d-1,对照组及模型组每日给予等量的蒸镏水。各组分别干预12周,观察24h尿蛋白定量、血肌酐（Scr）、尿素氮（BUN）的变化,同时行肾脏病理检查。结果：12周末,模型组大鼠24h尿蛋白定量、Scr、BUN均高于对照组（P〈0.05）。苯那普利组及益肾胶囊组24h尿蛋白定量、Scr、BUN均低于模型组（P〈0.05）。光镜下模型组大鼠肾小球系膜基质增多,系膜区增宽;电镜下模型组大鼠肾小球基底膜增厚,足细胞排列紊乱,数目减少,足突增宽、融合。苯那普利组及益肾胶囊组肾小球基底膜病变减轻,细胞外基质减少,足细胞数目增多,足突融合减轻。结论：益肾胶囊能降低尿蛋白排泄,改善肾功能,并对足细胞有一定的保护作用,从而延缓大鼠糖尿病大鼠肾脏损害。     

贝那普利联合曲尼司特对糖尿病肾脏疾病大鼠尿蛋白排泄率的影响

目的 探讨贝那普利联合曲尼司特对糖尿病肾脏疾病（diabetic kidney disease,DKD）大鼠尿蛋白排泄率的影响.方法 选择雄性SD大鼠40只,采用随机数字表法随机分为正常对照组10只,手术组30只,手术组应用单侧肾切除加高糖高脂饮食加小剂量链脲佐菌素（streptozotocin,STZ;40 mg/kg）方法制备糖尿病肾脏疾病大鼠模型,模型建立成功后再采用随机数字表法分为糖尿病肾脏疾病模型组（DKD组）、贝那普利用药组（B组）、贝那普利＋曲尼司特联合用药组（BQ组）,每组10只.B组在模型建立成功后予贝那普利10 mg·kg-1·d-1灌胃,BQ组在模型建立成功后予以曲尼司特（400 mg·kg-1·d-1）＋贝那普利（10 mg·kg-1·d-1）灌胃.于用药治疗开始后第12周末观察各组大鼠尿蛋白排泄率（urinary albumin excretion rate,UAER）、血肌酐（SCr）、尿素氮（BUN）及肾脏病理的变化.结果 与正常对照组相比,DKD组UAER明显增高（P＜0.05）,肾小球硬化程度较重（P＜0.05）;与B组相比,BQ组UAER更显著降低（P＜0.05）,肾小球硬化程度也显著降低（P＜0.05）.结论 贝那普利联合曲尼司特对DKD大鼠有明显的保护作用,其作用机制可能与降低UAER相关,并在一定程度上抑制肾间质纤维化.     

Perioperative and long-term morbidity and mortality after above-knee and below-knee amputations in diabetics and nondiabetics

We performed a retrospective review of a vascular surgery quality assurance database to evaluate the perioperative and long-term morbidity and mortality of above-knee amputations (AKA, n = 234) and below-knee amputations (BKA, n = 720) and to examine the effect of diabetes mellitus (DM) (181 of AKA and 606 of BKA patients). All patients in the database who had AKA or BKA from 1990 to May 2001 were included in the study. Perioperative 30-day cardiac morbidity and mortality and 3-yr and 10-yr mortality after AKA or BKA were assessed. The effect of DM on 30-day cardiac outcome was assessed by multivariate logistic regression and the effect on long-term survival was assessed by Cox regression analysis. The perioperative cardiac event rate (cardiac death or nonfatal myocardial infarction) was at least 6.8% after AKA and at most 3.6% after BKA. Median survival was significantly less after AKA (20 mo) than BKA (52 mo) (P < 0.001). DM was not a significant predictor of perioperative 30-day mortality (odds ratio, 0.76 [0.39-1.49]; P = 0.43) or 3-yr survival (Hazard ratio, 1.03 [0.86-1.24]; P = 0.72) but predicted 10-yr mortality (Hazard ratio, 1.34 [1.04-1.73]; P = 0.026). Significant predictors of the 30-day perioperative mortality were the site of amputation (odds ratio, 4.35 [2.56-7.14]; P < 0.001) and history of renal insufficiency (odds ratio, 2.15 [1.13-4.08]; P = 0.019). AKA should be triaged as a high-risk surgery while BKA is an intermediate-risk surgery. Long-term survival after AKA or BKA is poor, regardless of the presence of DM.     

Body composition assessment and methodology in nonathletic and athletic adolescent and adult males and females

The purpose of this review is to outline methodology for assessing body composition utilizing anthropometric and densitometric techniques. The objective of body composition assessment is to measure body fat and lean body mass. The quantity of these components varies due to growth, physical activity, dietary regimens, and aging. Anthropometric techniques incorporate selected skinfolds, circumferences, skeletal widths, or other variables to estimate body composition within k2.0-4.0%. These techniques are adequate for field testing of groups or individuals, but are population specific. Densitometry measures body volume irrespective of physique, sex, or age. This laboratory technique estimates body composition within 1.0-2.0%, is more difficult to administer, but is not population specific. Some limitation exists with any present technique due to biological variability and incomplete research of reference body composition in children, females, and the aged. J Orthop Sports Phys Ther 1984;5(6):336-347.     

Postoperative nausea and vomiting and opioid-induced nausea and vomiting: guidelines for prevention and treatment

Postoperative nausea and vomiting (PONV) causes patient discomfort, lowers patient satisfaction, and increases care requirements. Opioid-induced nausea and vomiting (OINV) may also occur if opioids are used to treat postoperative pain. These guidelines aim to provide recommendations for the prevention and treatment of both problems. A working group was established in accordance with the charter of the Sociedad Espa?ola de Anestesiología y Reanimación. The group undertook the critical appraisal of articles relevant to the management of PONV and OINV in adults and children early and late in the perioperative period. Discussions led to recommendations, summarized as follows: 1) Risk for PONV should be assessed in all patients undergoing surgery; 2 easy-to-use scales are useful for risk assessment: the Apfel scale for adults and the Eberhart scale for children. 2) Measures to reduce baseline risk should be used for adults at moderate or high risk and all children. 3) Pharmacologic prophylaxis with 1 drug is useful for patients at low risk (Apfel or Eberhart 1) who are to receive general anesthesia; patients with higher levels of risk should receive prophylaxis with 2 or more drugs and baseline risk should be reduced (multimodal approach). 4) Dexamethasone, droperidol, and ondansetron (or other setrons) have similar levels of efficacy; drug choice should be made based on individual patient factors. 5) The drug prescribed for treating PONV should preferably be different from the one used for prophylaxis; ondansetron is the most effective drug for treating PONV. 6) Risk for PONV should be assessed before discharge after outpatient surgery or on the ward for hospitalized patients; there is no evidence that late preventive strategies are effective. 7) The drug of choice for preventing OINV is droperidol.