Establishment of an Infected Necrotizing Pancreatitis Model by Retrograde Pancreatic Duct Injection of Sodium Taurocholate and E. coli in Rats

A stable and reliable infected necrotizing pancreatitis （INP） model in rats was established in order to study the pathophysiological mechanism and pathological development role of INP and explore the new therapeutic methods for the diseases. Forty-six SD rats were randomly divided into 5 groups. The animals in group A received the injection of 5% sodium taurocholate into the pancreatic duct and those in group B underwent that of E. coli into the pancreatic duct. The rats in groups C, D and E were subjected to the injection of 5% sodium taurocholate in combination with different concentrations of E. coli （10^3, 10^4, 10^5/mE, respectively） into the pancreatic duct. The dose of injection was 0.1 mL/100 g and the velocity of injection was 0.2 mL/min in all the 5 groups. Eight h after the injection, the survival rate of animals was recorded and the surviving rats were killed to determine the serum content of amylase and perform pathological examination and germ cultivation of the pancreatic tissue. The results showed that acute necrotizing pancreatitis model was induced by injection of 5% sodium taurocholate into the pancreatic duct. The positive rate of germ cultivation in group A was 12.5%. The acute necrotizing pancreatitis model was not induced by injection of E. coli into the pancreatic duct and the positive rate of germ cultivation in group B was 0. The INP model was established in groups C to E. The positive rate of germ cultivation was 60%, 100% and 100% and 8-h survival-rate 100%, 100% and 70% in groups C, D and E, respectively. It was concluded that a stable and reliable model of INP was established by injection of 5% sodium taurocholate in combination with 10^4/mL E. coli into the pancreatic duct with a dose of 0.1 mL/100 g and a velocity of 0.2 mL/min. The pathogenesis of INP might be that the hemorrhage and necrosis of pancreatic tissue induced by sodium taurocholate results in weakness of pancreatic tissue in fighting against the germs. Meanwhile, the necrotic pancreatic tissue provides a good proliferative environment for the germs.

Preparation method of an ideal model of multiple organ injury of rat with severe acute pancreatitis

AIM： To establish an ideal model of multiple organ injury of rats with severe acute pancreatitis （SAP）.METHODS： SAP models were induced by retrograde injection of 0.1 mL/100 g 3.5% sodium taurocholate into the biliopancreatic duct of Sprague-Dawley rats. The plasma and samples of multiple organ tissues of rats were collected at 3, 6 and 12 h after modeling. The ascites volume, ascites/body weight ratio, and contents of amylase, endotoxin, endothelin-1 （ET-1）, nitrogen monoxidum （NO）, phospholipase A2 （PLA2）, tumor necrosis factor-α （TNF-α）, interleukin-6 （IL-6） in plasma were determined. The histological changes of multiple organs were observed under light microscope.RESULTS： The ascites volume, ascites/body weight ratio, and contents of various inflammatory mediators in blood were higher in the model group than in the sham operation group at all time points [2.38 （1.10）, 2.58 （0.70）, 2.54 （0.71） vs 0.20 （0.04）, 0.30 （0.30）, 0.22 （0.10） at 3, 6 and 12 h in ascites/body weight ratio; 1582 （284）, 1769 （362）, 1618 （302） （U/L） vs 5303 （1373）, 6276 （1029）, 7538 （2934） （U/L） at 3, 6 and 12 h in Amylase; 0.016 （0.005）, 0.016 （0.010）, 0.014 （0.015） （EU/mL） vs 0,053 （0.029）, 0.059 （0.037）, 0.060 （0.022） （EU/mL） at 3, 6 and 12 h in Endotoxin; 3.900 （3.200）, 4.000 （1.700）, 5.300 （3.000） （ng/L） vs 41.438 （37.721）, 92.151 （23.119）, 65.016 （26.806） （ng/L） at 3, 6 and 12 h in TNF-α, all P 〈 0.01]. Visible congestion, edema and lamellar necrosis and massive leukocytic infiltration were found in the pancreas of rats of model group. There were also pathological changes of lung, liver, kidney, ileum, lymphonode, thymus, myocardium and brain.CONCLUSION： This rat model features reliability, convenience and a high achievement ratio. Complicated with multiple organ injury, it is an ideal animal model of SAR

Pancreatic blood perfusion in sodium taurocholate－induced pancreatitis in rats

The alterations of mean arterial pressure, pancreatic microflow, serum amylase and lipase,and pancreatic histology were studied in 42 rats in acute necrotizing pancreatitis induced by various concentrations of sodium taurocholate. The results showed that disturbance of pancreatic microflow which was shown by diminished pancreatic microflow occurred dramatically in the early stage of acute pancreatitis (AP) when mean arterial pressure remained stable, as concentration of the inducer increased,levels of serum amylase and lipase increased, pancreatic pathology worsened, and disturbance of pancreatic microflow further evolved. It is suggested that disturbance of pancreatic microflow might occur in the early stage of AP; disturbance of pancreatic microflow might be coincident with the pancreatic enzymes which were directly released into the blood stream during pancreatitis and with the severity of pancreatitis.

Effects of octreotide on acute necrotizing pancreatitis in rabbits

AIM:To assess the role of oxygen-derived free radicals and cytokines in the pathogenesis of taurocholic acid-induced acute pancreatitis,and to evaluate the preventive effects of octreotide towards the development of acute pancreatitis. METHODS:Acute pancreatitis was induced in male New Zealand white rabbits by retrograde injection of 0.8 mL/kg·b.m,of 50 g/L sodium taurocholate (NaTC) in the pancreatic duct.Sham- operated animals served as control.Octreotide i mg/kg·b.m. was administered subcutaneously before the induction of pancreatitis.Blood was taken from the jugular vein before and at 1,3,6,12 and 24 h after pancreatitis induction. Serum activities of amylase,IL-6 and TNF-α and levels of malonyl dialdehyde (MDA),glutathione (GSH),glutathione peroxidase (GPx),catalase and superoxide dismutase (Mn-, Cu-,and Zn-SOD) in pancreatic tissue were measured. RESULTS:Serum TNF-α and IL-6 levels increased significantly 3 h after the onset of pancreatitis,and then returned to control level.The tissue concentration of MDA was significantly elevated at 24 h,while the GSH level and GP-x,catalase,Mn-SOD,Cu-,Zn-SOD activities were all significantly decreased in animals with pancreatitis as compared to the control.Octreotide pretreatmnent significantly reversed the changes in cytokines and reactive oxygen metabolites.Octreotide treatment did not alter the serum amylase activity and did not have any beneficial effects on the development of histopathological changes. CONCLUSION:Oxygen-derived free radicals and proinflammatory cytokines are generated at an early stage of NaTc-induced acute pancreatitis in rabbits.Prophylactic octreotide treatment can prevent release of cytokines and generation of reactive oxygen metabolites,but does not have any beneficial effects on the development of necrotizing pancreatitis.

Stress kinase inhibition modulates acute experimental pancreatitis

AIM: To examine the role of p38 during acute experimental cerulein pancreatitis. METHODS: Rats were treated with cerulein with or without a specific JNK inhibitor (CEP1347) and/or a specific p38 inhibitor (SB203580) and pancreatic stress kinase activity was determined. Parameters to assess pancreatitis included trypsin, amylase, lipase, pancreatic weight and histology. RESULTS: JNK inhibition with CEP1347 ameliorated pancreatitis, reducing pancreatic edema. In contrast, p38 inhibition with SB203580 aggravated pancreatitis with higher trypsin levels and, with induction of acinar necrosis not normally found after cerulein hyperstimulation. Simultaneous treatment with both CEP1347 and SB203580 mutually abolished the effects of either compound on cerulein pancreatitis. CONCLUSION: Stress kinases modulate pancreatitis differentially. JNK seems to promote pancreatitis development, possibly by supporting inflammatory reactions such as edema formation while its inhibition ameliorates pancreatitis. In contrast, p38 may help reduce organ destruction while inhibition of p38 during induction of cerulein pancreatitis leads to the occurrence of acinar necrosis.

Sodium butyrate protects against toxin-induced acute liver failure in rats

BACKGROUND: Acute liver failure(ALF) is a serious clinical syndrome with high mortality. Sodium butyrate has been shown to alleviate organ injury in a wide variety of preclinical models of critical diseases. The aim of this study was to investigate the protective effect of sodium butyrate on ALF in rats.METHODS: All rats were randomly divided into control,model and sodium butyrate treatment groups. Except the control group, the rats were induced ALF animal model by subcutaneous injection of human serum albumin+D- galactosamine+lipopolysaccharide. After induction of ALF,the rats in the treatment group received sodium butyrate(500mg/kg) at 12-hour or 24-hour time point. Fourty-eight hours after ALF induction, the animals were sacrificed and samples were harvested. Serum endotoxin, high mobility group box-1(HMGB1), liver function parameters, tumor necrosis factoralpha(TNF-α) and interferon-gamma(IFN-γ) were measured.The expression of HMGB1 and nuclear factor-kappa B(NF-κB)p65 protein in liver tissue was detected by Western blotting. The histological changes of liver and intestine were examined. The survival duration was also observed.RESULTS: Serum endotoxin, alanine aminotransferase, HMGB1,TNF-α and IFN-γ were significantly increased and the liver histology showed more severe histopathological injury in the model group compared with the control group(P<0.05).Compared to the model group, sodium butyrate treatment significantly improved the histopathological changes in the liver and intestine, reduced serum endotoxin and inflammatory cytokines, suppressed HMGB1 and NF-кB p65 proteins in liver tissue, and prolonged the survival duration regardless of treatment at 12 hours or 24 hours after induction of ALF(P<0.05).CONCLUSIONS: Sodium butyrate protected the liver from toxin-induced ALF in rats. The mechanisms may be due to direct hepatoprotection and decreased intestinal permeability.

Experimental research on production and uptake sites of TNFα in rats with acute hemorrhagic necrotic pancreatitis

AIM To determine the site of production and uptake of tumor necrotic factor alpha (TNFα), and evaluate the relationship between serum TNFα and plasma endotoxin (ET) in rats with acute hemorrhagic necrotic pancreatitis (AHNP). METHODS Sprague Dawley rats were divided into AHNP group and control group ( n =12). AHNP model was induced by retrograde injection of 5% sodium taurocholate via pancreatic bile duct. The blood samples were obtained through portal vein 2 and 6 hours after the operation. RESULTS The contents of TNFα in portal vein were increased rapidly in the development of AHNP. They were lower in hepatic vein (280 59±20 02) and femoral artery (310 82±7 97) than in portal vein (354 91±25 50) ( P <0 05), and higher in femoral artery than in hepatic vein 6 hours after the operation ( P <0 05). TNFα level in plasma was increased significantly when ET level in portal vein showed no increase. CONCLUSION Pancreas, spleen, liver, intestinal tract and lung are the main organs to produce TNFα, and liver is also an important site for TNFα uptake in the development of AHNP. Plasma endotoxin is not a trigger for TNFα release in rats with AHNP.

L-arginine-induced experimental pancreatitis

Despite medical treatment,the lethality of severe acute pancreatitis is still high (20-30%).Therefore,it is very important to find good animal models to characterise the events of this severe disease.In 1984,Mizunuma et al. developed a new type of experimental necrotizing pancreatitis by intraperitoneal administration of a high dose of L-arginine in rats.This non-invasive model is highly reproducible and produces selective,dose-dependent acinar cell necrosis. Not only is this a good model to study the pathomechanisms of acute necrotizing pancreatitis,but it is also excellent to observe and influence the time course changes of the disease.By writing this review we iluminate some new aspects of cell physiology and pathology of acute necrotizing pancreatitis.Unfortunately,the reviews about acute experimental pancreatitis usually did not discuss this model. Therefore,the aim of this manuscript was to summarise the observations and address some challenges for the future in L-arginine-induced pancreatitis.

3种经典急性胰腺炎模型中回肠和胰腺抗菌肽的动态变化

背景:肠道菌群紊乱以及肠道屏障受损导致的细菌移位参与了急性胰腺炎(AP)的重症化进程。抗菌肽参与调节肠道菌群,但其在AP病程中的变化和作用尚不明确。目的:探究3种经典AP模型中回肠和胰腺抗菌肽的动态变化和意义。方法:构建雨蛙肽+脂多糖(CAE+LPS)、牛磺胆酸钠(N⁃Tau)和L⁃精氨酸(L⁃Arg)AP小鼠模型,评估胰腺和回肠组织病理学变化,以real⁃time PCR检测促炎细胞因子和抗菌肽,包括溶菌酶(LZM)、分泌型磷脂酶A2(sPLA2)、血管生成素4(Ang4)、再生胰岛衍生蛋白3(REG3)家族、β防御素家族、cathelicidin相关抗菌肽(CRAMP)、糖蛋白2(GP2)在回肠和(或)胰腺组织中的表达,分析抗菌肽表达与胰腺、回肠病理损伤的相关性。结果:3组AP模型组胰腺和回肠组织在各时间点均可观察到不同程度的病理损伤;在72 h内,CAE+LPS和N⁃Tau模型组病理损伤达峰值后开始减轻,L⁃Arg模型组病理损伤则逐渐加重。与相应对照组相比,3组AP模型组回肠组织LZM、sPLA2、Ang4和胰腺组织CRAMP、GP2、β防御素mRNA表达整体上显著下调(P均<0.05),CAE+LPS和N⁃Tau模型组呈先下降后回升趋势,L⁃Arg模型组则持续下降;回肠组织REG3β、REG3γmRNA表达在48 h或24 h显著上调达峰值后于72 h显著下调(P均<0.05),胰腺组织两者表达整体上显著上调(P均<0.05),但CAE+LPS和N⁃Tau模型组72 h时已回落;回肠组织β防御素mRNA表达在病程早期(12 h)显著上调(P均<0.05)后逐渐下降。Spearman相关系数分析表明,3种造模方式下,回肠LZM、sPLA2、Ang4和胰腺CRAMP、GP2、β防御素表达与胰腺、回肠病理损伤呈显著负相关(P均<0.05),胰腺REG3β表达则与胰腺、回肠病理损伤呈显著正相关(P均<0.05)。结论:在3种经典AP模型中,回肠LZM、sPLA2、Ang4和胰腺CRAMP、GP2、β防御素家族、REG3β表达均随AP病情严重程度呈动态变化,回肠和胰腺抗菌肽可能通过调节肠道微生态影响AP时的胰腺和肠道损伤。

三种急性胰腺炎大鼠模型的制备及特点比较

背景:建立稳定可靠的急性胰腺炎动物模型对于了解其发病机制、病理生理学特点及临床用药具有重大意义。国内外研究表明,雨蛙素、L-精氨酸、牛磺胆酸钠均能诱导急性胰腺炎,但是其病理生理学特点、模型特点变化规律尚不明确。目的:采用雨蛙素、L-精氨酸、牛磺胆酸钠制备大鼠急性胰腺炎模型,观察不同时段模型特点变化规律。方法:96只健康雄性SD大鼠随机分为正常组、雨蛙素组、L-精氨组、牛磺胆酸组,每组24只,每组内分为12,24,48 h 3个亚组,每个亚组8只。正常组不做处理,其余3组制备急性胰腺炎模型:雨蛙素组采用雨蛙素6次腹腔注射,间隔1 h;L-精氨酸组采用L-精氨酸2次腹腔注射,间隔1 h;牛磺胆酸钠采用胆胰管逆行注射牛磺胆酸钠诱导急性胰腺炎模型。考察各组大鼠存活率、胰腺大体形态、胰腺脏器指数、淀粉酶、脂肪酶、谷丙转氨酶、谷草转氨酶、尿素氮、肌酐水平,苏木精-伊红染色观察胰腺组织病理特征并进行胰腺损伤评分,评估大鼠不同时段模型特点变化规律。结果与结论:(1)雨蛙素组大鼠总存活率100%,L-精氨酸组为88%,牛磺胆酸钠组为96%;(2)各组模型大鼠胰腺脏器指数均有所升高;雨蛙素组大体观察可见胰腺水肿、分叶模糊、疏松;L-精氨酸组胰腺腺体增大增厚并伴有点片状出血;牛磺胆酸钠胰腺组织出现不同程度充血水肿伴散在点片状出血坏死;(3)各组模型组大鼠血清谷丙转氨酶、谷草转氨酶、尿素氮、肌酐水平与淀粉酶、脂肪酶水平变化一致,雨蛙素组可能在12 h达到峰值(P <0.05),随后呈下降趋势;L-精氨酸24 h达到最高峰(P <0.05),48 h明显下降;牛磺胆酸钠组血清淀粉酶、脂肪酶在12 h维持在较高水平并且有缓慢下降的趋势(P <0.05);(4)与正常组相比,光镜下观察雨蛙素组胰腺腺泡轻度水肿,小叶间隙增宽,炎性细胞较多;L-精氨酸组小叶间隙增宽,大量炎性细胞浸润,片状坏死点;牛磺胆酸钠组胰腺水肿明显,结构紊乱,出现大量坏死灶及炎性细胞浸润;(5)与正常组相比,3种模型诱导急性胰腺炎胰腺病理评分在各个时间点差异均有显著性意义(P <0.05),且同组随着时间的推移病理评分增加,说明胰腺组织损害逐渐加重;同一时间不同模型组相比,病理评分存在差异,且以牛磺胆酸钠组病理评分最高,L-精氨酸组次之,雨蛙素组最低;(6)结果提示,在相同时间点分析3种模型,病情最重的是牛磺胆酸钠组,以胰腺的出血坏死为主要特征;其次是L-精氨酸组,以坏死为主要特征,病情最轻为雨蛙素组,以水肿为主要特征;雨蛙素和L-精氨酸组血清生化指标在48 h有所好转,提示这两种模型可能有自愈倾向属于自限性病程;牛磺胆酸钠组血清生化指标在12 h后缓慢下降,因此认为在48 h后或者更长时间内牛磺胆酸钠组胰腺的损伤可能不会有所缓解。

肠壁穿刺逆行胰胆管注射牛黄胆酸钠重症急性胰腺炎造模

目的建立一种操作简单、病变典型且稳定性好的大鼠重症急性胰腺炎(SAP)模型。方法46只健康雄性SD大鼠分为SAP组和对照组,SAP组经肠壁穿刺逆行胰胆管注射5%牛黄胆酸钠,对照组同法注射等量0.9%生理盐水。两组大鼠分别于注射后3、6、12 h检测血清淀粉酶水平、胰腺组织的湿/干质量比率及病理组织学评分,观察24 h生存指数。结果SAP组各时间段血清淀粉酶和胰腺病理组织学评分均显著高于对照组,胰腺组织湿/干质量比率在注射后6、12 h显著高于对照组;其造模后24 h的总死亡率为70%(7/10)。结论经肠壁穿刺逆行胰胆管注射牛黄胆酸钠成功诱发大鼠SAP,其模型操作简单、可重复性好。

三种不同造模方法建立大鼠急性胰腺炎模型的对比

目的采用雨蛙肽、L-精氨酸、牛磺胆酸钠作为诱导剂建立大鼠急性胰腺炎(AP)动物模型,通过大鼠病理评分、血清生化及炎症细胞因子指标检测,找出一种操作简单、重复性好的大鼠AP造模方法。方法采用不用造模方法处理后的大鼠在不同时间点采集血液及胰腺标本。检测指标有淀粉酶(AMY)、谷丙转氨酶(ALT)、尿素氮(BUN)、肌酐(Cr)、Ca^(2+)、超氧化物歧化酶(SOD)、白介素(IL)-6、IL-10、肿瘤坏死因子(TNF)-α及胰腺组织病理评分。结果雨蛙肽组大鼠血清检查结果及胰腺病理均符合轻型AP改变,L-精氨酸及牛磺胆酸钠组血清检查结果及胰腺病理均符合重症AP改变。结论三种方法均可成模,大鼠AP模型病情最重的是牛磺胆酸钠诱导组,其次为L-精氨酸诱导组,病情最轻为雨蛙肽诱导组。

IL-8、IL-10在大鼠急性胰腺炎并发肺损伤中的作用

目的 探讨IL- 8、IL- 10在大鼠胰腺炎肺损伤中的作用。方法 采用胰胆管逆行注射3.5%牛磺胆酸钠的方法,制作大鼠重症急性胰腺炎并发肺损伤模型。分别对胰腺损伤、肺损伤程度进行病理评分,测定肺组织湿/干质量比;ELISA法测定大鼠血清IL- 8、IL -10水平。结果 造模后1 h,大鼠即出现较明显的胰腺损伤,随着时间的延长,胰腺损伤逐渐加重,以12 h为最。造模后1 h,即出现肺损伤,光镜下表现为白细胞浸润、肺泡间隔增厚、肺水肿及肺泡腔萎陷;至4 h肺组织湿/干质量比开始增加,此后,肺损伤程度逐渐增加,以24 h为最。造模后1 h,大鼠血清IL- 8、IL- 10水平逐渐升高,至24h达最高。结论 IL -8、IL- 10参与了大鼠胰腺炎肺损伤的病理过程,胰腺炎肺损伤的过程可能是体内全身性炎症反应综合征(SIRS)和代偿性抗炎症反应综合征(CARS)失衡的结果。

逆行胰胆管注射牛磺胆酸钠诱导重症急性胰腺炎模型多器官损害观察

探索逆行胰胆管注射牛磺胆酸钠诱导大鼠重症急性胰腺炎(Severe acute pancreatitis,SAP)模型及胰腺外多器官损害情况。采用12周龄SD大鼠35只,随机分为对照组和模型组,各3组。模型组逆行胰胆管注射牛磺胆酸钠诱导大鼠重症急性胰腺炎模型,对照组仅开腹后拨动十二指肠降部。观察造模后6 h、12 h胰腺和腺外器官病理和血清学指标、腹水及48 h内生存率。结果:SAP模型大鼠48 h内90%死亡,胰腺进行性水肿、坏死,大量腹水渗出,心、肺、肝、肾均有不同程度受损。SD大鼠逆行胰胆管注射牛磺胆酸钠诱导的动物模型,是研究重症急性胰腺炎胰腺坏死、水肿和多器官进损害的良好模型。

牛磺胆酸钠致急性胰腺炎时大鼠胰腺微血流的变化

作者观察了４２只大鼠用不同浓度牛磺胆酸钠诱导的急性出血坏死性胰腺炎时平均动脉压、胰腺微区血流量、血清淀粉酶和脂肪酶及胰腺病理形态的变化。发现在大鼠胰腺炎早期，平均动脉压尚无明显改变时，胰腺微区血流量降低：且随着诱导剂浓度的增加，血清淀份酶和脂肪酶进一步升高，胰腺病理损害加重，胰腺微血流进一步恶化。表明胰腺炎早期即可出现明显的胰腺微血流障碍；胰腺微血流障碍的程度与胰腺炎时释放入血的胰酶及胰腺炎的严重程度一致。

L-精氨酸诱导大鼠急性坏死性胰腺炎模型的建立

目的建立一种简便、典型的大鼠急性坏死性胰腺炎(ANP)模型。方法大鼠腹腔内分两次注射大剂量0.574mmol.L-1(10%)L-精氨酸,注射后3、12、24和36h观察胰腺病理变化、血清淀粉酶和丙二醛水平。结果胰腺病理评分、血清淀粉酶、丙二醛水平在3h开始升高,随后维持在较高的水平。结论腹腔内注射大剂量10%的L-精氨酸能诱导典型的大鼠ANP模型,是值得推广的造模方法。

大鼠重症急性胰腺炎模型制备方法的建立与探讨

目的建立一种操作简单,诱导成功率高且病变典型的重症急性胰腺炎(SAP)大鼠模型。方法 36只健康雄性SD大鼠随机分为模型组(n=18)和对照组(n=18)。模型组用微量输液泵经胰胆管逆行注入3.5%牛磺胆酸钠诱导SAP大鼠模型;对照组仅翻动胰腺和十二指肠。观察两组大鼠术后3h、6h、12h腹水及血清淀粉酶、脂肪酶的变化,观察胰腺组织大体形态以及病理改变,并进行评分。结果模型组胰腺组织结构破坏明显,其大体及病理评分均显著高于对照组(P<0.01),腹水量、血清淀粉酶、脂肪酶也均较对照组显著增加(P<0.01)。结论逆行胰胆管注射牛磺胆酸钠能成功诱导大鼠SAP,具有创伤小、操作简便、可重复性好及诱导成功率高的特点,是一种较为理想的SAP动物模型制备方法 。

重症急性胰腺炎对血清胰岛素和胰高血糖素影响的实验研究

目的研究重症急性胰腺炎对血清胰岛素和胰高血糖素的影响。方法应用3.5%牛磺胆酸钠逆行注入大鼠胰胆管,制作大鼠重症急性胰腺炎6h、24h、48h、72h动物模型,对胰腺病理损伤评分;免疫组化方法观察胰腺Bcl-2表达情况;放射免疫分析法测定血清胰岛素、胰高血糖素水平。结果重症急性胰腺炎大鼠造模后,随时间延长胰腺损伤加重,以24h为最;重症急性胰腺炎组大鼠血清胰岛素水平与实验对照组、正常对照组在24h、48h、72h相比明显下降,差异有统计学意义(P<0.05)。重症急性胰腺炎大鼠血清胰高血糖素水平制模后6h、24h、48h、72h与实验对照组、正常对照组相比明显升高,差异有统计学意义(P<0.05)。结论重症急性胰腺炎对胰腺内分泌有较大影响,在重症急性胰腺炎早期内分泌功能损伤的同时,机体可能存在一定的保护机制,Bcl-2可能参与了保护作用。

三种不同严重程度大鼠重症胰腺炎模型比较研究

目的为研究者选择合适的牛磺胆酸钠浓度来制备大鼠重症胰腺炎(severe acute pancreatitis,SAP)SAP模型提供依据。方法将60只SD大鼠随机分为假手术组、1.5%浓度组、3.5%浓度组和5%浓度组,造模各组分别用1.5%、3.5%和5%牛磺胆酸钠按逆行胆胰管注射法制备SAP模型。术后统计各组大鼠的死亡率;检测血清淀粉酶、肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)水平;观测各组大鼠胰腺组织HE染色病理评分。结果5%浓度组死亡率较1.5%浓度组显著升高,血淀粉酶、肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)水平、出血和腺泡组织坏死的病理评分较1.5%浓度组和3.5%浓度组均有显著升高。结论 5%的牛磺胆酸钠逆行胆胰管注射法能更好的制备SAP模型,且更符合SAP的生理、病理表现。

栀子对重症急性胰腺炎胰腺细胞结构和功能的影响及其与NO、内毒素、氧自由基的关系

目的探讨栀子对重症急性胰腺炎(SAP)胰腺细胞结构和功能的影响及其与一氧化氮(NO)、内毒素、氧自由基(OFR)的关系。方法经胆胰管逆行注射1.5%去氧胆酸钠建立SAP模型,给予栀子治疗,观察血中淀粉酶、内毒素、一氧化氮(NO)、过氧化脂质(LPO)以及胰腺细胞线粒体琥珀酸脱氢酶(SDH)活性、溶酶体酸性磷酸酶(ACP)释放率、微粒体细胞色素P450的变化,并进行相关分析及胰腺组织病理学检查。结果与对照组比较,模型组血中淀粉酶、NO、内毒素、LPO以及溶酶体ACP释放率明显升高(P<0.05),线粒体SDH活性和微粒体细胞色素P450则显著降低(P<0.05),光镜下胰腺组织病理损害明显;栀子治疗后上述各检测指标均较模型组明显改善(P<0.05);相关分析显示淀粉酶、NO、内毒素、LPO与溶酶体ACP释放率呈正相关,与线粒体SDH和微粒体细胞色素P450呈明显负相关。结论NO、内毒素、OFR破坏胰腺细胞的结构和功能。栀子能减轻三者的损伤,保护胰腺细胞。