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[实验性急性胰腺炎中的肝脏病变。胰腺酶储存减少的影响]

[Hepatic lesion in experimental acute pancreatitis. Influence of pancreatic enzyme storage reduction].

作者信息

Coelho A M, Machado M C, Sampietre S N, Leite K R, Molan N A, Pinotti H W

机构信息

Departamento de Gastroenterologia da Faculdade de Medicina da Universidade de São Paulo.

出版信息

Rev Hosp Clin Fac Med Sao Paulo. 1998 May-Jun;53(3):104-9.

Abstract

Acute Pancreatitis (AP) is known to produce morphologic and functional changes in liver. Administration of low doses of caerulein significant decreases the content of pancreatic enzymes, leading to reduced mortality of animals submitted to AP. The present study was designed to assess the effect of acute reduction of pancreatic enzymatic content in the hepatic mitochondrial function. Wistar male rats, submitted to AP by injection of Na thaurocholate into the pancreatic duct, with and without previous i.v. injection of 0.133 microgram Kg-1h-1 of caerulein for three hours, were divided in four groups: Group I: No caerulein infusion and AP; Group II: Previous caerulein infusion and with AP; Group III: Caerulein infusion without AP; Group IV (control): No caerulein infusion and without AP. After 2 hours of induction of AP the livers were removed and prepared to the mitochondrial oxidative and phosphorylative activities, measured polarographically with determination of oxygen consumption without ADP (Basal respiration-State 4) and in the presence of ADP (Activated respiration-State 3). Ascitic fluid contents of amylase, trypsin and total protein were routinely determined. After 2 hours of AP there was a significant increase in state 4 respiration (41%) and a decrease in respiratory control ratio and in ADP/O ratio (p < 0.05) in animals of Group I (AP without caerulein) when compared to Group II (AP with caerulein) (Table 1). Ascitic fluids contents of amylase (A) and trypsin (T) showed decrease in animals of Group II with AP that received previous caerulein infusion (A = 80 +/- 10 U/ml, T = 9.75 +/- 1.25 U/ml), when compared to animals of Group I that did not receive caerulein (A = 231 +/- 24, T = 40.32 +/- 5.19) (p < 0.001). Caerulein infusion by itself (Group III) did not have any influence on mitochondrial liver dysfunction. Reduction of pancreatic enzyme content through caerulein infusion attenuates the damage of mitochondrial respiration, demonstrated by uncoupling phase on mitochondrial function in experimental AP. Further studies are needed to elucidate this phenomena, but it is probably related to the decreased of the pathogenic effects of pancreatic activated enzymes that reach the systemic circulation in reduced amounts.

摘要

已知急性胰腺炎(AP)会引起肝脏的形态和功能变化。给予低剂量的雨蛙肽可显著降低胰腺酶的含量,从而降低患AP动物的死亡率。本研究旨在评估急性降低胰腺酶含量对肝线粒体功能的影响。将通过向胰管注射牛磺胆酸钠诱导AP的Wistar雄性大鼠分为四组,其中两组在诱导AP前静脉注射0.133微克/千克/小时的雨蛙肽,持续三小时:第一组:未输注雨蛙肽且患有AP;第二组:先前输注雨蛙肽且患有AP;第三组:输注雨蛙肽但无AP;第四组(对照组):未输注雨蛙肽且无AP。诱导AP两小时后,取出肝脏并准备测量线粒体的氧化和磷酸化活性,通过极谱法测定无ADP时的耗氧量(基础呼吸 - 状态4)和存在ADP时的耗氧量(激活呼吸 - 状态3)。常规测定腹水淀粉酶、胰蛋白酶和总蛋白的含量。与第二组(输注雨蛙肽且患有AP)相比,第一组(未输注雨蛙肽且患有AP)在AP两小时后,状态4呼吸显著增加(41%),呼吸控制率和ADP/O比值降低(p < 0.05)(表1)。与未接受雨蛙肽的第一组动物(淀粉酶 = 231 ± 24,胰蛋白酶 = 40.32 ± 5.19)相比,先前接受雨蛙肽输注且患有AP的第二组动物的腹水淀粉酶(A)和胰蛋白酶(T)含量降低(A = 80 ± 10 U/ml,T = 9.75 ± 1.25 U/ml)(p < 0.001)。单独输注雨蛙肽(第三组)对线粒体肝功能障碍没有任何影响。通过输注雨蛙肽降低胰腺酶含量可减轻线粒体呼吸损伤,这在实验性AP中线粒体功能的解偶联阶段得到证明。需要进一步研究来阐明这一现象,但这可能与到达体循环的胰腺激活酶的致病作用减少有关。

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