P-selectin、IVAM-1和ICAM-1在大鼠重症急性胰腺炎并发急性心肌损害中的作用机制

目的:研究大鼠重症急性胰腺炎(SAP)并发急性心肌损害(AMD)时心肌组织黏附分子(P-selectin、VCAM-1、ICAM-1)基因表达的变化以及丹红注射液对表达的影响.方法:90只S-D大鼠随机分为对照组(A组,n=30)、SAP模型组(B组,n=30)和治疗组(C组,n=30),采用腹腔注射L-Arg的制作S...     

PEP-1-SOD1对SAP大鼠细胞凋亡的影响

背景:重度急性胰腺炎(SAP)以胰腺弥漫性出血和组织坏死为特征,具有很高的死亡率。PEP-1-SOD1是一种利用基因工程技术合成的融合蛋白,稳定性较高,具有一定的抗炎作用。目的:探讨PEP-1-SOD1对SAP大鼠细胞凋亡的影响。方法:将24只雄性Wistar大鼠分为对照组、SAP组和实验组。以5%牛磺胆酸钠制备SAP大鼠模型,实验组在造模前30 min腹部皮下注射8. 0 mg/kg PEP-1-SOD1,SAP组注射同剂量0. 9%NaC l溶液。行组织病理学评分,以TUNEL法检测胰腺腺泡细胞凋亡情况,分别以荧光定量PCR和蛋白质印迹法检测caspase-3 mRNA和蛋白表达。结果:造模后24 h,SAP组和实验组大鼠血清脂肪酶、淀粉酶水平、caspase-3 mRNA和蛋白表达均显著高于对照组(P 0. 05),而实验组血清脂肪酶、淀粉酶显著低于SAP组(P 0. 05),caspase-3 mRNA和蛋白表达显著升高(P 0. 05)。造模后6 h、24 h,SAP组和实验组胰腺组织病理学评分、凋亡指数显著高于对照组(P 0. 05),而实验组组织病理学评分显著低于SAP组(P 0. 05),凋亡指数显著升高(P 0. 05)。结论:PEP-1-SOD1可通过调控凋亡相关基因caspase-3的表达,减轻SAP大鼠胰腺组织病理损害,增加胰腺腺泡细胞凋亡,促进胰腺功能恢复正常。     

SOCS3在重症急性胰腺炎大鼠胰腺中的表达和作用

目的:探讨细胞因子信号转导抑制子3(SOCS3)在实验生重症急性胰腺炎(SAP)中的表达和作用.方法:32只♂ Sprague-Dawley大鼠随机分为对照组(NC组)和3组SAP 6 h、12 h、18h组,每组8只.以4％牛磺胆酸钠胰胆管逆行注射诱导SAP模型,动态测定各组血清淀粉酶(AMY)水平;光镜下观察胰腺大...     

氧化苦参碱对葡聚糖硫酸钠诱导大鼠结肠炎的抗炎作用机制研究

目的　探讨氧化苦参碱 (OM )对葡聚糖硫酸钠 (DSS)诱导结肠炎的抗炎作用及其作用机制。方法　建立DSS诱导的大鼠结肠炎模型。SD大鼠 2 6只 ,随机分为OM处理组 (A组 ,10只 )、OM未处理组 (B组 ,10只 )和正常对照组 (C组 ,6只 )。A组第 1～ 11天肌内注射OM 6 3mg·kg-1·d-1,第 4～ 11天饮用 2 %DSS溶液 ;B组第 1～ 11天肌注与A组OM等体积的生理盐水 ,第 4～ 11天饮用 2 %DSS溶液 ;C组肌注生理盐水同B组 ,正常饮水。观察大鼠的腹泻、便血症状及结肠组织学改变 ,ELISA测定血清肿瘤坏死因子 α(TNF α)和白细胞介素 6 (IL 6 )水平 ,免疫组化检测结肠黏膜核转录因子 κB(NF κB)活性及细胞间粘附分子 1(ICAM 1)的表达。结果　与OM未处理组相比 ,OM处理组大鼠的症状和结肠黏膜组织学损伤显著改善 (P值均 <0 .0 5 ) ,TNF α ,IL 6 ,NF κB和ICAM 1显著降低 (P值均 <0 .0 5 )。结论　OM可抑制NF κB活化 ,降低TNF α、IL 6和ICAM 1的生成 ,从而减轻结肠炎性损伤和腹泻、便血症状。     

甘氨酸对重症急性胰腺炎肺组织中髓样细胞触发受体-1mRNA及高迁移率族蛋白-1表达的影响及临床意义

目的探讨甘氨酸对重症急性胰腺炎(SAP)肺组织中髓样细胞触发受体(TREM)-1与高迁移率族蛋白(HMGB)-1表达的影响及临床意义。方法将81只SD大鼠随机分成对照组、SAP组和甘氨酸组,每组27只。对照组常规开腹后仅移动肠管,SAP组常规开腹后进行胰管穿刺并注入5%牛磺胆酸钠溶液建立SAP大鼠模型,甘氨酸组在建立SAP大鼠模型前3、6 h分别从尾部静脉注入甘氨酸。在建模成功后的第6、12、24 h从三组大鼠中随机选择9只进行剖腹获取完整肺部组织以测定TREM-1 mRNA和HMGB-1水平。结果 SAP组TREM-1 mRNA的表达水平逐渐上升,且6、12、24 h的TREM-1 mRNA表达水平均显著高于对照组和甘氨酸组(P0.05),12 h和24 h的HMGB-1表达水平均显著高于对照组和甘氨酸组(P0.05);而甘氨酸组6、12、24 h的TREM-1mRNA和HMGB-1的表达水平均与对照组比较无统计学意义(P0.05)。结论甘氨酸对SAP肺组织具有一定的保护作用,可显著降低肺组织中TREM-1 mRNA和HMGB-1的表达。     

重症急性胰腺炎大鼠血清白细胞介素-2、-8及-10的表达及临床意义

目的探讨重症急性胰腺炎(SAP)大鼠血清中白细胞介素(IL)-2、-8、-10的表达及临床意义。方法 45只SD雄性大鼠,按照随机数字表法分为对照组、假手术组、SAP组各15只,SAP组切开大鼠腹部暴露胰腺,按照大鼠体重1 ml/kg剂量胆总管注入50 g/L牛磺胆酸钠制备SAP模型,假手术组手术相同但不注射药物,对照组正常饲养,光镜观察大鼠胰腺组织改变,酶联免疫吸附(ELISA)法在大鼠建模成功后12 h测定IL-2、IL-8及IL-10表达。结果光镜下观察SAP组胰腺组织严重水肿,细胞坏死,具有片状血斑或者胰腺出现局部皂化斑,其中SAP组胰腺组织病理为(9.45±1.45)分,SAP组评分明显高于对照组和假手术组(P0.05)。大鼠建模成功后及对照组12 h后三组IL-2、IL-8及IL-10表达水平差异显著(P0.05),其中SAP组IL-2、IL-8水平高于假手术组和对照组,IL-10水平低于假手术组和对照组(P0.05)。SAP组血清IL-2、IL-8水平与胰腺组织病理学评分呈明显正相关(r=0.567,0.675;P=0.012,0.004),与IL-10呈负相关(r=-0.896,P=0.000)。结论 IL-2、IL-8及IL-10等在SAP早期诊断中起着重要作用,并且可以作为疾病严重程度和治疗效果评价指标。     

高迁移率族蛋白B1在重症急性胰腺炎肠屏障损害中的作用

目的:探讨高迁移率族蛋白B1在重症急性胰腺炎(SAP)肠屏障损害中的作用及其机制.方法:采用逆行胆胰管注射50 g/L牛磺胆酸钠制备SAP大鼠模型.将56只Wistar大鼠随机分为正常对照组(Control组),SAP 3h,6h,12h,24h,48h 5个亚组,二硫代氨基甲酸吡咯烷处理组(PDTC组),每组8只.PDTC组于建模后24h取材.测定血浆内毒素(LPs)、二胺氧化酶(DAO)水平,用逆转录-聚合酶链反应(RT-PCR)方法检测肠组织高迁移率族蛋白B1(HMGB1)mRNA表达,用Western blot法检测肠组织HMGB1水平.结果:与对照组比较,SAP 6h组大鼠肠组织HMGB 1 mRNA表达显著增高(0.41±0.06 vs 0.26±0.03,P<0.01),12h呈现进一步升高趋势,24h达峰值(0.62±0.06),并持续至48h.PDTC干预可显著降低肠组织HMGB1 mRNA表达(0.35±0.06 vs 0.62±0.06,P<0.01).PDTC组较SAP 24h组肠组织HMGB1 mRNA表达,血浆LPS和DAO显著下降(HMGB1 mRNA表达:0.35±0.06 vs 0.62±0.06,P<0.01;LPS:0.433±0.120 KEU/L vs 0.852±0.232 KEU/L,P<0.01;DAO:0.65±0.12 kU/L vs 1.36±0.22 kU/L,P<0.01).结论:SAP时,肠组织内HMGB1表达上调;PDTC可以明显抑制SAP时肠组织内HMGB1表达.     

金黄益胆颗粒对重症急性胰腺炎大鼠胰腺组织中ICAM-1、TGF-β1表达的影响

目的:探讨金黄益胆颗粒对重症急性胰腺炎(SAP)大鼠胰腺组织中细胞间黏附分子1(ICAM-1)、转化生长因子β1(TGF-β1)表达的影响.方法:清洁级SD♂大鼠54只,随机分为对照组、模型组、治疗组,每组18只,各组又分为2h组、6h组及12h组3个时间段组,每个时间段组6只大鼠.5%牛磺胆酸钠逆行注射建立SAP大鼠动物模型.行胰腺组织镜下病理评分,免疫组织化学SP两步法检测胰腺组织中ICAM-1、TGF-β1蛋白的表达.结果:Schmidt胰腺组织镜下评分显示,与模型组比较,造模后6h、12h,治疗组大鼠胰腺组织的病理损害程度明显减轻(10.33±0.82vs14.00±0.63,P=0.000;9.67±0.82vs15.33±0.52,P=0.000).治疗组12h后ICAM-1阳性细胞表达明显减少(3.67±0.76vs6.40±0.72,P=0.000).治疗组6h和12h后TGF-β1表达明显增强(3.77±0.78vs0.60±1.00;5.17±1.42vs2.23±1.01,均P=0.000).结论:金黄益胆颗粒能够降低ICAM-1的表达,升高TGF-β1的表达,显著改善早期SAP大鼠胰腺...     

P38MAPK通路对SAP大鼠模型海马神经元诱导型一氧化氮合酶和前列腺素E2表达的影响

目的:研究P38丝裂原活化蛋白激酶(mitogenactivated protein kinase,MAPK)通路在急性重症胰腺炎(severe acute pancreatitis,SAP)大鼠模型海马神经元中对诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)和前列腺素E2(prostaglandin E2,PGE2)的作用.方法:将60只SD大鼠随机分为对照组、SAP模型组(模型组)、抑制剂组(P38MAPK通路抑制剂SB203580).Nissl染色、免疫组织化学显色、免疫印迹法检测大鼠海马CA1区iNOS、PGE2和p-P38表达的变化;应用透射电镜观察胰腺组织超微结构的变化.结果:与对照组相比,SAP模型组海马CA1区p-P38(20.4±2.2 vs 2.1±1.3)、i NOS(33.6±4.4 vs 3.7±0.4)、PGE2(34.7±4.0 vs 2.4±1.0)阳性神经元的数量显著增加(P0.05);给予S B203580后,抑制剂组海马C A1区p-P3 8(1 2.8±0.7)、iNOS(1 4.4±4.9)、P G E2(18.3±0.5)阳性神经元的数量明显减少(P0.05).模型组胰腺细胞粗面内质网脱颗粒,线粒体水肿扩张,抑制剂组上述改变明显减轻.结论:P38丝裂原活化蛋白激酶通路对SAP大鼠模型海马i NOS和PGE2表达可能起调控作用,抑制该通路对SAP大鼠具有神经保护作用.     

趋化因子CXCL11及其受体CXCR3在重症急性胰腺炎相关肺损害中的作用

目的:制作大鼠重症急性胰腺炎(severe acute pancreatitis,SAP)模型,检测不同时间点趋化因子CXCL11及其受体CXCR3在SAP肺组织中的动态变化,探讨他们在SAP肺功能损害过程中的作用.方法:48只SD大鼠,雌雄不限,随机分为2组:对照组(C组),SAP组(P组),每组24只.4%牛黄胆酸钠逆行胰胆管注射建立SAP大鼠模型,剂量为1mL/kg,C组打开腹腔后仅仅翻动胰腺组织数次.每组随机分为4个亚组,每个亚组6只.4个组分别在1、3、6、12h抽血、处死,留取组织标本.分别检测各不同时间点组的血清淀粉酶、肺湿干重比,胰腺组织、肺组织病理,免疫组织化学法检测肺CXCL11及CXCR3的表达,酶联免疫吸附试验(ELISA)检测血清中的CXCL11的水平.结果:P组各亚组血清淀粉酶值明显升高(P<0.01vsC组);肺湿干重比值:P组3、6、12h组较C组明显升高(P<0.05);胰腺组织、肺组织病理:3、6、12hP组肺组织损伤明显;免疫组织化学显示P组CXCL11与CXCR3蛋白表达较C组表达明显增强(P<0.05),ELISA显示:1、3、6、12hP组血清CXCL11蛋白较C组明显增高(P<0.01).结论:CXCL11/CXCR3可能参与大鼠SAP急性肺功能损害的发病过程.     

还原性谷胱甘肽对重症急性胰腺炎大鼠早期胰肝损伤的保护作用

目的阐明还原性谷胱甘肽对重症急性胰腺炎早期胰肝损害的保护作用。方法 54只雄性Wistar大鼠随机分三组,每组18只:A组为正常对照组,开腹后仅翻动胰腺,即关腹;B组为重症急性胰腺炎(SAP)组,以0.1 mL/min的速度向胰胆管内逆行注入4.5%牛磺胆酸钠(1 mL/kg)建立大鼠SAP模型;C组为N-乙酰半胱氨酸(NAC)处理组,术前0.5 h,用NAC(200 mg/kg)腹腔注射,接着建立大鼠SAP模型。于造模术后6 h,麻醉大鼠获取新鲜胰腺和肝脏组织,取一部分用于GSH检测,另一部分用于病理学观察和电镜观察。结果胰腺组织中还原性谷胱甘肽(GSH)水平为:对照组>NAC处理组>SAP组,差异有统计学意义(P<0.05)。胰腺组织病理学检查及评分:SAP组和NAC处理组大鼠出现急性坏死性胰腺炎病变,但NAC处理组胰腺组织坏死比SAP组胰腺组织坏死程度减轻。SAP与NAC处理组比较差异有统计学意义(P=0.0368,P<0.05)。6 h电镜观察:N-乙酰半胱氨酸能改善胰腺腺泡细胞内酶原颗粒运转,肝脏超微结构显示,SAP组内质网扩张,线粒体肿胀,NAC处理组局部可见内质网扩张。结论随着GSH的消耗,发病早期(6 h)就可以出现胰肝损害,补充N-乙酰半胱氨酸能减轻胰腺和肝脏的损害。     

Delayed ethyl pyruvate therapy attenuates experimental severe acute pancreatitis via reduced serum high mobility group box 1 levels in rats

AIM： To investigate the effect of delayed ethyl pyruvate （EP） delivery on distant organ injury, survival time and serum high mobility group box 1 （HMGB1） levels in rats with experimental severe acute pancreatitis （SAP）.
METHODS： A SAP model was induced by retrograde injection of artificial bile into the pancreatic ducts of rats. Animals were divided randomly into three groups （n = 32 in each group）： sham group, SAP group and delayed EP treatment group. The rats in the delayed EP treatment group received EP （30 mg/kg） at 12 h, 18 h and 30 h after induction of SAP. Animals were sacrificed, and samples were obtained at 24 h and 48 h after induction of SAP. Serum HMGB1, aspartate arninotransferase （AST）, alanine arninotransferase （ALT）, blood urea nitrogen （BUN）, and creatinine （Cr） levels were measured. Lung wet-to-dry-weight （W/D） ratios and histological scores were calculated to evaluate lung injury. Additional experiments were performed between SAP and delayed EP treatment groups to study the influence of EP on survival times of SAP rats.
RESULTS： Delayed EP treatment significantly reduced serum HMGB1 levels, and protected against liver, renal and lung injury with reduced lung W/D ratios （8.22 ±0.42 vs 9.76 ± 0.45, P 〈 0.01）, pulmonary histological scores （7.1 ± 0.7 vs 8.4 ± 1.1, P 〈 0.01）, serum AST （667 ± 103 vs 1 368 ± 271, P 〈 0.01）, ALT （446 ± 91 vs 653 ± 98, P 〈 0.01） and Cr （1.2 ± 0.3 vs 1.8 ± 0.3, P 〈 0.01） levels. SAP rats had a median survival time of 44 h. Delayed EP treatment significantly prolonged median survival time to 72 h （P 〈 0.01）.
CONCLUSION： Delayed EP therapy protects against distant organ injury and prolongs survival time via reduced serum HMGBllevels in rats with experimental SAP. EP may potentially serve as an effective new therapeutic option against the inflammatory response and multiple organ dysfunction syndrome （MODS） in SAP patients.     

Activated protein C,an anticoagulant polypeptide,ameliorates severe acute pancreatitis via regulation of mitogen-activated protein kinases

Background Our aim was to investigate the changes of mitogen-activated protein kinases (MAPKs) by activated protein C (APC) treatment in rats with severe acute pancreatitis (SAP), and relate them to changes in SAP severity, thus providing evidence for developing clinical therapies. Methods Sprague-Dawley rats were given an intravenous injection of saline (SAP group), APC (50 μg/kg or 10 μg/kg), or CNI1493 just before SAP induction. One group of rats underwent a sham operation (control group). Experimental samples were harvested 16 h after SAP induction. The gene expression of pancreatic MAPKs was evaluated by cDNA microarrays. The mRNA and protein/phosphorylated protein levels of p38 MAPK, extracellular signal-regulated protein kinase (ERK) 1/2, and c-Jun N-terminal kinase (JNK) and the protein levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1β were determined in pancreatic tissue. The severity of disease was evaluated by pancreatic histology, the pancreatic wet/dry weight ratio, and the serum amylase level. Results In rats treated with APC (50 μg/kg) or CNI1493, the severity of pancreatitis and expression of pancreatic TNF-α and IL-1β proteins were attenuated by the decreased expression and activity of p38 MAPK and JNK (vs. the SAP group, P < 0.01). The expression and activity of ERK1/2 were increased in APC-treated rats, especially in the group treated with APC 50 μg/kg (vs. the SAP or CNI1493-treated group, P < 0.01, respectively). Conclusions Inhibition of expression of pancreatic p38 MAPK and JNK and upregulation of ERK1/2 expression by APC treatment may protect against pancreatic injury, thus ameliorating severity of the disease.     

白介素-18在急性胰腺炎大鼠中性粒细胞凋亡中的作用

目的:探讨白介素-18(IL-18)在重症急性胰腺炎(SAP)时外周血中性粒细胞(PMN)凋亡中的作用.方法:SD大鼠60只,随机分为2组,每组30只,分别建立大鼠急性坏死性胰腺炎组(ANP)及假手术组(SO)模型,在制模后3、6、12h分期分批处死大鼠,抽取下腔静脉血测定血淀粉酶含量及血清中IL-18的含量,作中性粒细胞分离并检测外周血中性粒细胞凋亡率;同时对大鼠胰腺组织行病理切片HE染色,并对胰腺组织进行病理评分.结果:ANP组中性粒细胞(PMN)凋亡率较SO组明显降低,并随着时间的延长逐渐明显(P<0.01),至术后12h降至2.15%±0.45%;ANP组血清中IL-18的含量较SO组明显升高,而且随着时间的延长更明显(P<0.01),在12h达到4705.70±296.30;ANP组PMN的凋亡率与血清中IL-18的水平呈负相关(r=-0.78,P<0.01).结论:ANP组外周血PMN的凋亡明显延迟,血清中IL-18的含量明显增高,IL-18可能在急性胰腺炎外周血的PMN凋亡中发挥作用.     

Adenoviral transfer of human interleukin-10 gene in lethal pancreatitis

AIM: To evaluate the therapeutic effect of adenoviral-vector-delivered human interleukin-10 (hIL-10) gene on severe acute pancreatitis (SAP) rats. METHODS: Healthy Sprague-Dawley (SD) rats were intraperitoneally injected with adenoviral IL-10 gene (AdvhIL-10), empty vector (Adv0) or PBS solution. Blood, liver, pancreas and lung were harvested on the second day to examine hIL-10 level by ELISA and serum amylase by enzymatic assay. A SAP model was induced by retrograde injection of sodium taurocholate through pancreatic duct. SAP rats were then administered with AdvhIL-10, Adv0and PBS solution by a single intraperitoneal injection 20 min after SAP induction. In addition to serum amylase assay, levels of hIL-10 and tumor necrosis factor-α (TNF-α) were detected by RT-PCR, ELISA and histological study. The mortality rate was studied and analyzed by Kaplan-Meier and log rank analysis.RESULTS: The levels of hIL-10 in the pancreas, liver and lung of healthy rats increased significantly after AdvhIL-10 injection (1.42 ng/g in liver, 0.91 ng/g in pancreas); while there was no significant change of hIL-10 in the other two control groups. The concentration of hIL-10 was increased significantly in the SAP rats after AdvhIL-10 injection (1.68 ng/g in liver, 1.12 ng/g in pancreas) compared to the other two SAP groups with blank vector or PBS treatment (P&lt;0.05). The serum amylase levels remained normal in the AdvhIL-10 transfected healthy rats. However, the serum amylase level was significantly elevated in the other two control SAP rats. In contrast, serum amylase was down-regulated in the AdvhIL-10 treated SAP groups.The TNF-α expression in the AdvhIL-10 treated SAP rats was significantly lower compared to the other two control SAP groups. The pathohistological changes in the AdvhIL-10 treated group were better than those in the other two control groups. Furthermore, the mortality of the AdvhIL-10 treated group was significantly reduced compared to the other two control groups (P&lt;0.05). CONCLUSION: Adenoviral hIL-10 gene can significantly attenuate the severity of SAP rats, and can be used in the treatment of acute inflammation process.     

Effect of severe acute pancreatitis on pharmacokinetics of Da-Cheng-Qi Decoction components

AIM: To investigate the effect of severe acute pancreatitis (SAP) on pharmacokinetics of Da-Cheng-Qi Decoction (DCQD) components in rats. METHODS: Rats were divided into SAP group and sham-operation group as a control group ( n = 6). Rhein, chrysophanol, rheochrysidin, magnolol, hesperidin and naringin in DCQD were quantified in rat serum by high performance liquid chromatography tandem mass spectrometry for studying their pharmacokinetics. RESULTS: Early absorption of each DCQD component was tended to degrade in SAP group after treatment with DCQD by gavage. The Cmax (chrysophanol, P = 0.0059; rheochrysidin, P = 0.0288; magnolol, P = 0.0487; hesperidin, P = 0.0277; naringin, P = 0.0023) and AUC (rhein, P = 0.0186; chrysophanol, P = 0.0013; magnolol, P = 0.001; hesperidin, P = 0.0081; naringin, P = 0.0272) of DCQD component were obviously lower in SAP group than in control group. The T1/2α of chrysophanol and rheochrysidin ( P = 0.0467 and 0.0005, respectively) and Tmax of chrysophanol and rheochrysidin ( P = 0.0101 and 0.0037, respectively) lasted longer in SAP group than in control group. CONCLUSION: SAP can significantly impact the absorption of DCQD components in rats and their pharmacokinetic parameters.     

Hepatic effect of NAC on sevear acute pancteatise of rats

Objective:To analyze the hepatic protection of n-acetvl cysteine(NAC)on severe acute pancreatitis(SAP).Methods:SD rats were randomly divided into control group,SAP group and NAC group.SAP AHO method was adopted to establish the model,2 h after modeling,rats in NAC group had intraperitoneal injection of NAC(200 mg/kg).Ten rals from each group were sacrifieed in even'6 and 12 h at different time[mints respectively.Liver damage,liver function and serum amylase,AST,ALT and malondialdehyde(MDA)were determined.Results:Serum amylase,AST,AIT and MDA content in SAP,NAC group at each time point were significantly higher in the control group(P0.05),serum amylase,AST,ALT and MDA content in NAC group rats were lower in the SAP group significantly(P0.05);Microscopic examination showed that the liver injury in rats and the NAC group significantly reduced in the SAP group.Conclusions:NAC provides effective protection against liver damage to SAP,protective from SAP liver injury.     

低分子肝素对伴高脂血症急性坏死性胰腺炎大鼠PAF、ET-1/NO的影响

目的:研究低分子肝素(LMWH)治疗伴高脂血症性急性胰腺炎(HL-AP)大鼠微循环障碍的作用.方法:SD大鼠80只,高脂饲料喂养4wk建立高脂血症模型后,随机分成3组:假手术(S)组,n=16;NS对照(N)组,n=32;低分子肝素(L)组,n=32.N组与L组大鼠建立ANP模型,S组大鼠仅开腹翻动胰腺.L组造模后分别于0h,6h,12h及18h开始使用LMWH皮下注射.N、S组同时点同方法用生理盐水对照,24h后抽门静脉检测血小板活化因子(PAF)、内皮素-1(ET-1)/一氧化氮(NO)浓度并行电镜观察胰腺组织微循环结构.结果:L组PAF、ET-1/NO浓度分别为5.9250mmol/L±0.6113mmol/L及3.5368±0.26;N组为7.4059mmol/L±0.4281mmol/L及4.1697±0.08;SO组为4.4950mmol/L±0.2628mmol/L及2.5133±0.20;L组PAF、ET-1/NO浓度均低于N组但高于SO组,有统计学意义;L组中0h及6h开始用LMWH的大鼠PAF、ET-1/NO浓度低于12h及18h组,有统计学意义.电镜观察L组胰腺病变程度轻于N组.结论:高脂血症急性胰腺炎大鼠存在胰腺微循环障碍;LMWH可以改善高脂血症大鼠SAP胰腺微循环障碍,并且早期应用优于晚期应用.     

Effect of salvia miltiorrhizae on apoptosis and NF-κB p65 expression in the liver of rats with severe acute pancreatitis or obstructive jaundice

Objective: To investigate the therapeutic effects and mechanism of salvia miltiorrhizae in the treatment of severe acute pancreatitis (SAP) or obstructive jaundice (OJ). Methods: SAP rat models were prepared and randomly divided into the model control group and treated group. The sham‐operated group was also set. At 3 h, 6 h and 12 h after operation, the mortality rate, the pathological changes in the liver, the contents of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum, the expression levels of Bax and NF‐κB p65 proteins in the liver, and the apoptosis index of hepatic cells in SAP rats in each group were observed. On days 7, 14, 21 and 28 after operation, the above parameters and the contents of TBILI (total billirubin), DBILI (direct bilirubin) and r‐GT (r‐glutamyl transpeptidase) in serum in OJ rats were observed. Results: The contents of serum ALT (at 6 h and 12 h after operation) and AST (at 3 h and 12 h after operation) as well as the staining intensity of NF‐κB p65 protein (at 12 h after operation) in the liver of SAP rats in the treated group were significantly lower than those in model control group (all P < 0.01). The pathological severity scores (on 21 d and 28 d after operation) in the liver, the contents of serum ALT (on 14 d and 21 d after operation), AST (on 21 d after operation), TBILI (on 21 d and 28 d after operation), DBILI (on 28 d after operation) and r‐GT (on 21 d after operation), and the apoptosis index of hepatic cells in OJ rats in treated group were significantly lower than those in model control group (all P < 0.05). The positive rates of Bax protein (on 28 d after operation) in treated group was significantly lower than model control group (P < 0.05). Conclusions: Salvia miltiorrhizae is able to improve the liver function of SAP or OJ rats, suppress the expression of NF‐κB p65 protein in the liver of SAP rats, and inhibit apoptosis in OJ rats, thereby showing some protective effects on the liver of SAP or OJ rats.