胰腺炎相关性腹水诱导的大鼠胰腺病理学改变

目的观察胰腺炎相关性腹水(pancreatitis associated ascetic fluid,PAAF)腹腔注射后引起的胰腺病理学改变。方法SD大鼠26只,随机分为急性出血坏死性胰腺炎组(acute hemorrhagic necrotic pancreatitis,AHNP)(AHNP组,n=10),生理盐水(normal saline,NS)组(NS组,n=8)以及PAAF组(n=8)。制备急性出血坏死性胰腺炎腹水后,腹腔注射到健康大鼠体内,7h后活杀,取胰腺进行光镜以及电镜观察。结果PAAF组胰腺病理改变表现为腺泡细胞完整,腺叶间隔略增宽。结论PAAF腹腔注射后引起的胰腺病理改变轻微。     

重症急性胰腺炎腹水对正常肾细胞影响

目的通过观察重症急性胰腺炎(SAP)腹水对正常肾细胞影响,探讨SAP时急性肾功能损伤的机制。方法SD大鼠54只分成SAP组(n=30)和假手术组(n=24),SAP组以5%牛磺酸胆酸钠溶液胆管逆行注射诱导模型,术后6h、12h、24h采集血清、腹水。ELISA法检测血清、腹水TNFα水平,RT PCR检测肾细胞TNFαmRNA表达。将24h采集的血清和腹水处理体外培养NRK细胞,MTT法检测细胞活性,流式细胞术测定NRK细胞凋亡率。结果SAP组6h、12h、24h血清和腹水TNFα水平渐进性升高,各时间段差异显著(P<0.05)且较假手术后明显升高(P<0.01)。SAP组大鼠血清和腹水处理后NRK细胞活性均低于假手术组。SAP组大鼠腹水和血清处理24h后,NRK细胞培养液中TNFα水平较假手术组明显升高(P<0.01);NRK细胞TNFαmRNA表达上调,显著高于假手术组;凋亡率分别为29.67%±4.12%和59.95%±2.11%,假手术组大鼠血清和腹水处理24h凋亡率分别为3.72±2.90%和4.11±3.30%,差异显著(P<0.01)。结论SAP时肾损伤可能与肾细胞过度凋亡有关,而肾细胞过度凋亡与血清和腹水TNFα升高及肾细胞过多分泌TNFα有关,SAP腹水对肾的直接损伤可能比血清明显。     

腹腔注射胰腺炎相关性腹水与穿孔性腹膜炎腹水诱导大鼠急性肺损伤的对比研究

目的 通过腹腔注射胰腺炎相关性腹水(pancreatitis associated ascetic fluids,PAAF)和上消化道穿孔性腹膜炎腹水(perforative peritonitis ascitic fluids,PPAF)诱导急性肺损伤(acute lung injury,ALI),探讨腹腔注射PAAF诱导大鼠ALI的非特异性.方法 120只SD大鼠建立急性坏死性胰腺炎模型和消化道穿孔模型,收集PAAF和PPAF;48只大鼠随机分为生理盐水对照组(n=16),PAAF组(n=16)和PPAF组(n=16).各组大鼠随机分为7h、12h亚组.检测肺组织病理损害评分、肺组织湿/干比、肺组织髓过氧化物酶和肺细胞凋亡检测.结果 PAAF组和PPAF组各时间点肺组织髓过氧化物酶、肺组织病理损害评分、湿/干比和细胞凋亡率均高于对照组(P＜0.01),而PAAF组和PPAF组各指标间差异无统计学意义.结论 腹腔注射PAAF和PPAF均可诱导大鼠ALI,腹腔注射PAAF诱导大鼠ALI具有非特异性.     

L-精氨酸在人肝癌裸鼠肝脏移植瘤生长中的作用

目的 探讨L-精氨酸(L-arg)在人肝癌裸鼠肝脏移植瘤生长中的作用.方法 建立人肝癌裸鼠肝脏移植瘤模型,使用L-arg进行干预治疗,采用免疫组化方法 和图像分析技术检测增殖细胞核抗原(PCNA)的表达,原位末端标记(TUNEL)法检测肿瘤细胞的凋亡情况.结果 (1)小剂量L-arg(0.5 g·kg~(-1)·d~(-1))组、大剂量L-arg(1g·kg~(-1)·d~(-1))组和对照组移植瘤重量分别为(985±76)mg、(328±35)mg、(586±56)mg;大剂量L-arg组移植瘤重量较对照组显著减少(P＜0.05);小剂量L-arg组移植瘤重量较对照组显著增加(P＜0.05).(2)大剂量L-arg组移植瘤PCNA的表达较对照组显著下调(P＜0.05),小剂量L-arg组和对照组比较无明显差异(P＞0.05).(3)大剂量L-arg组NO水平较对照组和小剂量组显著升高(P＜0.05),小剂量L-arg较对照组显著升高(P＜0.05).(4)大剂量L-arg组移植瘤凋亡指数(AI)明显高于对照组(P＜0.05);小剂量L-arg对移植瘤AI无明显影响(P＞0.05).结论 L-精氨酸对肝癌具有双重作用.小剂量L-精氨酸可促进肝癌生长;大剂量L-精氨酸抑制肝癌的生长.     

L-精氨酸对局灶性脑缺血大鼠神经元凋亡的影响

目的 评价L-精氨酸(L-arg)对局灶性脑缺血大鼠神经元凋亡的影响.方法 健康雄性SD大鼠56只,体重250～300 g,随机分为7组(n=8):假手术组(SH组)、脑缺血2 h组(Is1组)、脑缺血2 h L-arg治疗组(L-arg1组)、脑缺血6 h组(IS2组)、脑缺血6 h L-arg治疗组(L-arg2组)、脑缺血12h组(IS3组)及脑缺血12 h L-arg治疗组(L-arg3组).采用线栓法制备大鼠大脑中动脉阻塞模型.各L-arg治疗组分别于脑缺血后腹腔注射L-精氨酸500 mg/kg,2次/d,治疗3 d;IS组给予等容量生理盐水.治疗3 d后取脑,测定缺血区域神经元凋亡率、Caspase-3蛋白、Bcl-2蛋白和Bax蛋白的表达水平.结果 与SH组比较,IS1组、IS2组和IS3组神经元凋亡率升高,Caspase-3蛋白和Bax蛋白表达上调,Bcl-2/Bax蛋白比值降低(P＜0.01);与IS1组和IS2组比较,L-arg1组和L-arg2组神经元凋亡率降低,Caspase-3蛋白和Bax蛋白表达下调,Bcl-2蛋白表达上调,Bcl-2/Bax蛋白比值升高(P＜0.01).IS3组与L-arg3组上述指标差异无统计学意义(P＞0.05).结论 L-arg可减少脑缺血早期大鼠神经元凋亡,具有一定的治疗作用,其机制可能与下调Caspase-3蛋白表达、调节Bcl-2/Bax蛋白平衡有关.     

丹参注射液对重症急性胰腺炎大鼠胰腺NF-κB活化的影响

目的观察重症急性胰腺炎（SAP）大鼠胰腺核因子-κB（NF-κB）活性的变化及丹参注射液对其的影响,从而探讨丹参注射液治疗急性胰腺炎的机理。方法将大鼠随机分为正常对照组、SAP组和丹参治疗组3组,采用腹腔和皮下同时注射L-精氨酸的方法制成大鼠急性胰腺炎模型,分别测量血浆、腹水淀粉酶,并采用免疫组化方法测定胰腺组织中NF-κB的表达。结果与正常对照组比较,SAP组血浆、腹水淀粉酶水平明显增高,胰腺组织NF-κB表达强度升高（P〈0.05）;丹参治疗组上述指标与SAP组相比均有明显下降（P〈0.05）,且胰腺的病理损伤减轻,存活时间更长。结论丹参注射液可能通过降低胰腺组织中NF-κB的表达而对急性胰腺炎的治疗发挥作用。     

胰腺炎相关性腹水诱导大鼠肺损伤模型的建立

目的 研究大鼠经腹腔内注射胰腺炎相关性腹水(pancreatitis associated ascetic fluid,PAAF)诱导的急性肺损伤模型,旨在探讨该模型的意义.方法 制备大鼠急性出血坏死性胰腺炎并收集PAAF.大鼠腹腔内注射PAAF诱导肺损伤,分别于注射后7 h、12 h活杀,观察肺组织结构以及胰腺病理学改变,并测定大鼠呼吸频率、动脉血气、外周血白细胞计数以及血清淀粉酶浓度.结果 腹腔注射PAAF后,大鼠呼吸频率加快,PaO2水平显著下降,外周血白细胞计数升高;肺组织出现明显的损伤,表现为肺间质水肿以及大量的炎性细胞浸润;而胰腺病理学上改变轻微.结论 建立了PAAF诱导的大鼠肺损伤模型.PAAF腹腔注射后引起的胰腺病变程度轻微,表明该模型能够一定程度上"屏蔽"胰腺病变对肺脏的影响,从而为研究肺损伤机制提供了比较单纯的研究背景.     

脂肪间充质干细胞对重症急性胰腺炎大鼠炎性损伤的调节作用

目的:探讨脂肪间充质干细胞(hADSC)对重症急性胰腺炎大鼠炎性损伤的调节作用以及相关机制。方法:将54只健康清洁级SD大鼠随机分为3组:正常对照组、SAP组、hADSC组,采用L-精氨酸溶液(20g/L)腹腔注射法建立重症急性胰腺炎(SAP)模型。SAP组、hADSC组分别通过尾静脉途径注入等量的PBS或hADSC,采用血清淀粉酶检测试剂盒(碘-淀粉比色法)检测血清淀粉酶水平;ELISA试剂盒检测血清TNF-α、IL-6水平;HE染色观察大鼠胰腺病理形态改变;实时定量PCR及免疫印迹法检测细胞核转录因子(NF-κB P65)表达情况。结果:SAP组大鼠血清淀粉酶、TNF-α、IL-6水平较正常对照组明显升高(P0.01),HE染色可见胰腺细胞水肿、坏死,炎性细胞大量浸润;NF-κB P65蛋白及m RNA表达显著上调(P0.01);hADSC组血清学指标较SAP组显著降低(P0.05),HE染色可见胰腺组织炎性损伤情况明显改善,Westernbolt及RT-qPCR结果显示NF-κB P65表达较SAP组显著下调(P0.05)。结论:hADSC能够抑制重症急性胰腺炎大鼠炎性反应水平,减轻胰腺炎性损伤,此过程可能与下调NF-κB P65表达有关。     

5-氟脲嘧啶预防重症急性胰腺炎早期肾损伤的免疫机制研究

目的探讨5-氟脲嘧啶(5-Fu)和奥曲肽(Oct)防治重症急性胰腺炎(SAP)肾损伤的免疫机制。方法逆行胰胆管注射牛黄胆酸建立大鼠SAP模型,随机分成生理盐水组(n=17),成模后静滴生理盐水;5-Fu组(n=20),5-Fu2mg/h持续静滴12h;奥曲肽组(n=18),Oct首剂2μg/100g,继以0.2μg/(100g·h)持续静滴12h,另设假手术组(n=10)。ELISA法检测4组大鼠成模后6h和12h血清TNF-α等系列细胞因子表达变化,TUNEL法检测大鼠肾组织凋亡率,RT-PCR法测定肾组织TNF-αmRNA表达。体外培养大鼠正常肾NRK细胞,用上述4组SAP大鼠血清分别置换培养液中小牛血清,流式细胞术检测处理后细胞凋亡率。结果5-Fu组和奥曲肽组血清TNF-α、IL-1和TXB2较生理盐水组均明显降低(P均<0.05),奥曲肽组PGE2水平明显升高(P<0.05)。5-Fu组和奥曲肽组肾组织凋亡率分别为(5.8±3.1)%和(4.6±3.1)%,显著低于生理盐水组(12.3±5.6)%(P<0.05),且两组TNF-αmRNA表达明显下降。生理盐水组、奥曲肽组、5-Fu组和假手术组大鼠血清处理后NRK细胞凋亡指数分别为(38.67±11.4)%、(20.4±18.4)%、(10.5±11.0)%和(1.7±2.2)%。生理盐水组与奥曲肽和5-Fu组差异有统计学意义(P<0.05)。结论5-Fu可通过降低血清炎性介质和细胞因子,减少肾细胞凋亡防治SAP急性肾损伤。     

奥曲肽对胰腺炎相关性腹水诱导的大鼠肝细胞凋亡的保护作用

目的探讨奥曲肽对胰腺炎相关性腹水(PAAF)诱导的大鼠肝细胞凋亡的保护作用及其相关机制。方法以PAAF诱导的大鼠肝损伤模型(B组)为研究对象,监测4、7h血清肝功能酶学指标(ALT、AST)、总胆红素(TBiL)、淀粉酶(AmYL)及转化生长因子(TGF)β1浓度。同时对胰腺、肝组织进行组织学观察;TUNEL法流式细胞术定量检测肝细胞凋亡情况,以及应用奥曲肽后(C组)对上述指标的变化。对比评估B组与急性坏死性胰腺炎模型(ANP组)胰腺损伤程度。结果B组各血清学指标均比空白对照组(A组)显著升高(P<0.01);C组上述各指标显著下降(P<0.01);ANP组与B组相比,7h时间点AmYL浓度明显升高(P<0.01)。PAAF诱导7h后(20.13±3.84)%的肝细胞发生凋亡,其中(49.04±1.44)%细胞生长停滞在G2/M期。电镜(TEM)下可见典型的晚期凋亡肝细胞;ANP组胰腺损伤程度明显重于B组。结论(1)TGFβ1在肝细胞增殖(G2/M)期诱导其凋亡损伤;(2)奥曲肽通过抑制TGFβ1在肝脏的表达而对PAAF诱导的大鼠肝细胞凋亡具有良好的保护作用;(3)PAAF诱导的大鼠肝损伤模型中的胰腺病变明显轻于ANP时的胰腺病变。     

Breakdown of intestinal mucosa via accelerated apoptosis increases intestinal permeability in experimental severe acute pancreatitis

BACKGROUND: Bacterial translocation plays an important role for infectious complications in severe acute pancreatitis (SAP). Breakdown of intestinal mucosal integrity may increase intestinal permeability and may be implicated in bacterial translocation. It is suggested that increase in intestinal permeability is correlated with the changes of tight junction and/or apoptosis in intestinal epithelial cells. The aim of this study was to investigate the changes of intestinal mucosa and its permeability in SAP. METHODS: SAP was induced by injection of 3% sodium deoxycholate into the biliopancreatic ducts in rats. Permeability of intestinal wall was assayed ex vivo by measuring the leaked amount of FITC-dextran from the ileum pouch. Alteration of tight junction proteins such as zonula occludens (ZO)-1 and Occludin was evaluated by Western blotting and immunofluorescence staining. Apoptotic change of intestinal mucosa was detected by TUNEL staining and DNA fragmentation ELISA. In vitro, apoptosis-inducing effect of pancreatitis-associated ascitic fluid (PAAF) was examined using T84 cells. Integrity of monolayer cells was assessed by transepithelial electric resistance (TEER). RESULTS: Permeability of ileum was significantly increased 6 h after induction of SAP. Blood endotoxin level was significantly elevated and bacterial translocation occurred 18 h after induction of SAP. Six hours after induction of SAP, expressions of ZO-1 and Occludin were not altered, but apoptosis of ileum mucosa was significantly accelerated. Addition of PAAF to T84 cells did not affect expressions of ZO-1 or Occludin, but significantly increased the apoptosis and significantly decreased TEER. CONCLUSIONS: These results suggest that breakdown of intestinal mucosa via accelerated apoptosis may increase in intestinal permeability in SAP and that PAAF contains factor(s) that accelerates the apoptosis of intestinal epithelial cells.     

胰腺炎相关性腹水诱导大鼠肝损伤的实验研究

目的 探讨胰腺炎相关性腹水(pancreatitis associated ascitic fluid,PAAF)诱导的大鼠肝损伤模型的胰腺和肝细胞的病理结构改变及其应用价值.方法 将PAAF按8 ml/只注射入SD大鼠腹腔内,注射后于第4,7小时分批处死动物.测定大鼠血清肝功能酶学指标丙氨酸氨基转移酶(alanine aminotrotransferase,ALT)、天门冬氨酸氨基转移酶(aspartateaminotrotransferase,AST)、总胆红素(total bilirubin,TBiL)及血清淀粉酶(amylase,AmYL)浓度.透射电子显微镜观察胰腺、肝组织亚细胞结构变化情况.结果 模型动物出现肝功能损害,其血清ALT,AST及TBiL显著升高;AmYL浓度则无明显改变.电镜下胰腺腺泡细胞仅见部分内质网扩张,线粒体轻度肿胀,而酶元颗粒胞膜保持完整;肝细胞出现凋亡表现,胞浆内有特异性的核碎片.结论 PAAF诱导的模型动物中的胰腺病变明显不同于急性坏死性胰腺炎(acute necrotizing pancreatitis,ANP)大鼠的胰腺病变,它可通过诱导细胞凋亡而导致大鼠肝损伤.     

早期大剂量甲强龙冲击治疗对大鼠重症急性胰腺炎的影响

目的 观察早期大剂量甲强龙冲击治疗对大鼠重症急性胰腺炎(SAP)炎症变化以及胰腺组织内T淋巴细胞浸润情况的影响.方法 通过腹腔内注射L-精氨酸(320 mg/100 g)制作大鼠重症胰腺炎模型,96只雄性SD大鼠随机分成正常对照组(NS组,n=32),重症急性胰腺炎组(SAP组,n=32),重症胰腺炎甲基强地松龙治疗组(MES组,n=32),观察SAP模型后6 h、12 h、24 h、72 h胰腺湿干比重、血清淀粉酶以及胰腺CD3~+、CD4~+、CD8~+T淋巴细胞及CD4~+/CD8~+比值变化水平.另外3组各取15只SD大鼠观察72h病死率.结果 SAP组较NS组各时段72 h病死率、血清淀粉酶、胰腺湿干比,而胰腺CD3~+、CD4~+、CD8~+T淋巴细胞百分数及CD4/CD8比值明显降低,MES组较SAP组各时段胰腺湿干比、血清淀粉酶明显降低,CD3~+、CD4~+、CD8~+T淋巴细胞百分数及CD4/CD8比值有所降低,但差异无统计学意义.结论 早期大剂量甲强龙冲击治疗重症急性胰腺炎对降低病死率,改善胰腺炎炎性介质反应具有明显作用,对内毒素水平、胰腺免疫功能影响无统计学意义.     

Hematin is one of the cytotoxic factors in pancreatitis-associated ascitic fluid that causes hepatocellular injury.

BACKGROUND: We recently demonstrated that pancreatitis-associated ascitic fluid (PAAF) contains cytotoxic factor(s), inducing apoptosis in hepatocytes, and that PAAF induces hepatic adenosine triphosphate depletion, hepatocellular acidosis, and accumulation of hepatic intracellular sodium. Because ascitic fluid and serum from patients with hemorrhagic pancreatitis contain a lot of hematin, we aimed to test the hypothesis that hematin can induce hepatocellular injury, and then we compared its cytotoxicity with that of PAAF. METHODS: In vivo effects of intraperitoneal injection of hematin into the liver of healthy rats were evaluated with in situ nick-end labeling, blood biochemical analysis, and nuclear magnetic resonance spectroscopy. In vitro cytotoxic and apoptosis-inducing activities of hematin on rat primary culture hepatocytes were investigated with a cellular proliferation assay kit and DNA fragmentation enzyme-linked immunosorbent assay, respectively. Furthermore, PAAF was fractionated with Sephacryl S-300 gel column chromatography, and cytotoxic activities of its fractions on a human hepatoma cell line (HuH-7) were compared with those of hematin. RESULTS: Intraperitoneal injection of hematin into healthy rats caused apoptosis in the hepatocytes and elevated serum glutamate oxaloacetic transaminase and lactate dehydrogenase levels. Intraperitoneal injection of hematin also caused a significant decrease in the hepatic beta-adenosine triphosphate/inorganic phosphate ratio, severe hepatic intracellular acidosis, and a significant increase of hepatic intracellular sodium (Na(+)) concentration, similar to the effects of PAAF. In vitro, hematin decreased hepatocyte viability and increased the DNA fragmentation of hepatocytes, similar to the effects of 10% PAAF. Albumin reversed the cytotoxic effects of hematin and PAAF on HuH-7 cells nearly completely and partially, respectively. Fractionation of PAAF and hematin by gel column chromatography revealed that the first peak of cytotoxic activity of PAAF corresponded to that of hematin and that the cytotoxic activity was reversed by albumin nearly completely. CONCLUSIONS: These results suggest that hematin is one of the cytotoxic factors in PAAF that causes hepatocellular injury and that cellular injuries caused by hematin may be involved in the development of multiple organ failure associated with severe acute pancreatitis.     

Apoptotic cell death of renal tubules in experimental severe acute pancreatitis

BACKGROUND: Recently renal cell apoptosis has been reported in various disorders that result in renal failure. Thus we hypothesized that renal cell injury resulting from apoptosis is involved in renal failure with severe acute pancreatitis. METHODS: Renal cell apoptosis in kidneys harvested from rats with necrotizing pancreatitis was evaluated by in situ nick-end labeling. Ascitic fluid that had been collected 6 hours after development of pancreatitis was injected into the peritoneal cavities of healthy rats, and renal apoptosis was also evaluated. The apoptosis-inducing activity of the ascitic fluid was estimated in vitro with use of isolated rat renal tubules and the normal rat kidney cell line NRK52E by nuclear staining, cell cycle analysis, and DNA electrophoresis. RESULTS: Apoptosis was detected by in situ nick-end labeling on the renal tubules 6 hours after induction of pancreatitis in vivo. Similar tubular apoptosis was detected in the rats that had intraperitoneal injection of the ascitic fluid. In in vitro analyses the ascitic fluid induced nuclear and DNA fragmentation on the isolated renal tubules and promoted apoptosis on NRK52E cells in a time-dependent manner. CONCLUSIONS: Apoptotic cell death of renal tubules occurs in severe acute pancreatitis within several hours and is possibly involved in the mechanism of renal failure through undefined substance(s) in the ascitic fluid associated with pancreatitis.     

Involvement of peritoneal macrophage in the induction of cytotoxicity due to apoptosis in ascitic fluid associated with severe acute pancreatitis

The aim of this study was to assess the significance of peritoneal macrophage in inducing cytotoxicity in ascitic fluid associated with severe acute pancreatitis. The involvement of peritoneal macrophage was examined experimentally in rats by macrophage depletion with peritoneal lavage prior to the development of pancreatitis. More than 94% of the cellular components collected from peritoneal cavities by the lavage are macrophages. Although the ascitic fluid collected from the rats with necrotizing pancreatitis showed cytocidal effects via apoptosis on Madin-Darby canine kidney cells in a dose- and time-dependent manner, cytotoxicity or apoptosis-inducing activity almost disappeared from the ascitic fluid by the preceding peritoneal lavage. The ascitic fluid did not show significant differences by the lavage in osmolarity and in concentrations of albumin, bilirubin, amylase, and lipase. Although a slight reduction of tumor necrosis factor-alpha was noted with the lavage, tumor necrosis factor-alpha failed to induce apoptotic cell death in the cells, and the neutralization by antibody ameliorated neither cell death nor apoptosis. We conclude that peritoneal macrophages secrete apoptosis-inducing factor(s) into pancreatitis-associated ascitic fluid, other than tumor necrosis factor-alpha.     

The role of nitric oxide in obstructive nephropathy

PURPOSE: Ureteral obstruction leads to tubulointerstitial fibrosis and loss of renal function. Nitric oxide production ameliorates fibrosis due to obstructive uropathy. However, nitric oxide is produced by 3 isoforms of the enzyme, nitric oxide synthase. We evaluated the role of inducible nitric oxide synthase in obstructive uropathy using nitric oxide synthase knockout mice, and determined whether the administration of L-arginine to promote nitric oxide synthesis by alternative nitric oxide synthase isoforms modulates renal fibrosis in these animals. MATERIALS AND METHODS: Complete unilateral ureteral obstruction was created in wild-type C57 and inducible nitric oxide synthase knockout mice. Control animals of each strain underwent sham surgery. Throughout the experiment mice had free access to untreated tap water or water supplemented with 10 gm./l. L-arginine. Animals were sacrificed 1 and 2 weeks, respectively, after creation of unilateral ureteral obstruction. We obtained serum as well as bladder and obstructed renal pelvic urine, and determined the nitrite level in each fluid. Renal cortical thickness was measured in the normal and obstructed kidneys. The degree of tubulointerstitial fibrosis was evaluated by trichrome staining and type I collagen deposition in kidney tissue specimens. RESULTS: Nitrite was significantly decreased in the serum, bladder and renal pelvic urine of inducible nitric oxide synthase knockout mice with unilateral ureteral obstruction compared with that in wild-type C57 mice at 1 and 2 weeks (p<0.05). In knockout mice with unilateral ureteral obstruction 1 week in duration that drank tap or L-arginine supplemented water nitrite in serum and each urine sample was higher than in sham operated knockout controls. The level returned to baseline after 2 weeks of obstruction (p<0.05). After 2 weeks of obstruction there was significantly greater cortical thinning in knockout than in C57 mice (p<0.05). Moreover, knockout mice given L-arginine supplemented water for 2 weeks had even greater cortical thinning than after 1 week or than mice given tap water for 1 to 2 weeks (p<0.05). Decreased renal cortical thickness in knockout mice after 2 weeks of obstruction was associated with less intense trichrome staining and a virtual absence of type I collagen deposition compared with findings in the wild-type C57 strain. CONCLUSIONS: Inducible nitric oxide synthase knockout mice with unilateral ureteral obstruction have significantly lower nitrite in serum and urine than wild-type C57 mice. Knockout mice also have more severe renal cortical thinning than C57 animals after creation of unilateral ureteral obstruction. Providing L-arginine supplemented water to inducible nitric oxide synthase knockout mice exacerbates the loss of cortical thickness. Alterations in cortical thinning that we observed in knockout mice were associated with decreased tubulointerstitial fibrosis and a decreased net renal extracellular matrix accumulation. These data indicate that endothelial or neuronal nitric oxide synthase may be more important than inducible nitric oxide synthase for modulating renal fibrosis in obstructive uropathy.     

左旋精氨酸对急性胰腺炎的作用

探讨左旋精氨酸（Ｌ－Ａｒｇ）在大鼠急性水肿性胰腺炎（ＡＥＰ）中的作用。方法观察倍数剂量Ｌ－Ａｒｇ治疗ＡＥＰ大鼠后,血浆和胰组织一氧化氮（ＮＯ）浓度、血浆淀粉酶、平均动脉压（ＭＡＰ）、胰组织病理的变化。结果ＡＥＰ大鼠血浆、胰组织ＮＯ浓度明显降低,Ｌ－Ａｒｇ５０、１００ｍｇ／ｋｇ升高血浆、胰组织ＮＯ浓度,改善了大鼠ＡＥＰ;Ｌ－Ａｒｇ８００、１６００ｍｇ／ｋｇ体重使ＮＯ浓度过度升高,加重ＡＥＰ成为急性出血坏死性胰腺炎（ＡＨＮＰ）;胰组织病理评分与血浆、胰组织ＮＯ浓度呈正相关。Ｌ－Ａｒｇ对ＭＡＰ的影响较小。血浆淀粉酶除８００ｍｇ／ｋｇ体重组明显降低外,其余各组间无明显差异。结论Ｌ－Ａｒｇ因升高ＮＯ浓度而参与了大鼠ＡＥＰ的病理过程。     

急性坏死性胰腺炎时NO变化及三七总甙的治疗作用

目的:探讨急性坏死性胰腺炎(ANP)大鼠体内一氧化氮(NO)在疾病发展过程中的变化规律,中药三七总甙对ANP的治疗作用及对NO的影响.方法:将120只SD大鼠随机分为假手术组、对照组及实验组,用5%牛磺胆酸钠制成ANP模型,实验组用三七总甙治疗,对照组不用药物治疗,分别于术后2 h、4 h、6 h、8 h、12 h、24 h测定血清及胰腺的NO含量,并比较生存率.结果:实验组和对照组术后2 h NO水平显著增高,8 h后开始降低,24 h仍高于正常水平.但实验组明显低于对照组,实验组的生存率亦明显高于对照组.1周生存率假手术组、ANP组、ANP 中药组分别为100%、0%、70%.结论:ANP时NO有显著变化,三七总甙对其有抑制作用,对ANP有显著的治疗作用.     

急性胰腺炎相关性腹腔积液研究进展

急性胰腺炎起病急、并发症多，是临床常见的急腹症。其中，重型急性胰腺炎常在病程早期出现胰腺炎相关性腹腔积液，也称为胰源性腹腔积液。目前，关于胰源性腹腔积液的研究已取得较大的进展。在各种病因诱导的急性胰腺炎病程早期，由于胰腺局部的炎症及继发扩大化的瀑布式炎症反应，引发胰腺及胰周组织渗出，以及炎症因子释放共同参与形成胰腺炎相关性腹腔积液。由于含有大量有害因子，胰腺炎相关性腹腔积液可经多种通路造成机体多器官功能损害，从而加重病情，这在大量的动物实验中已得到证实。目前已有不少学者强烈推荐通过微创化外科干预来处理胰腺炎相关性腹腔积液，以求改善病人预后。