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L-半胱氨酸对胆胰管梗阻诱导的重症急性胰腺炎大鼠远隔器官损伤的影响。

Effect of L-cysteine on remote organ injury in rats with severe acute pancreatitis induced by bile-pancreatic duct obstruction.

机构信息

Department of Gastroenterology, and Shanghai Key Laboratory of Pancreatic Diseases, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai 200080, China.

出版信息

Hepatobiliary Pancreat Dis Int. 2013 Aug;12(4):428-35. doi: 10.1016/s1499-3872(13)60067-3.

DOI:10.1016/s1499-3872(13)60067-3
PMID:23924502
Abstract

BACKGROUND

Remote organ failure occurs in cases of acute pancreatitis (AP); however, the reports on AP induced by pancreatic duct obstruction are rare. In this study we determined the effect of L-cysteine on pancreaticobiliary inflammation and remote organ damage in rats after pancreaticobiliary duct ligation (PBDL).

METHODS

AP was induced by PBDL in rats with 5/0 silk. Sixty rats were randomly divided into 4 groups. Groups A and B were sham-operated groups that received injections of saline or L-cysteine (10 mg/kg) intraperitoneally (15 rats in each group). Groups C and D were PBDL groups that received injections of saline or L-cysteine (10 mg/kg) intraperitoneally (15 rats in each group). The tissue samples of the pancreas and remote organs such as the lung, liver, intestine and kidney were subsequently examined for pathological changes under a light microscope. The samples were also stored for the determination of malondialdehyde and glutathione levels. Blood urea nitrogen (BUN), plasma amylase, ALT and AST levels were determined spectrophotometrically using an automated analyzer. Also, we evaluated the effect of L-cysteine on remote organ injury in rats with AP induced by retrograde infusion of 3.5% sodium taurocholate (NaTc) into the bile-pancreatic duct.

RESULTS

Varying degrees of injury in the pancreas, lung, liver, intestine and kidney were observed in the rats 24 hours after PBDL. The severity of injury to the lung, liver and intestine was attenuated, while injury status was not changed significantly in the pancreas and kidney after L-cysteine treatment. Oxidative stress was also affected by L-cysteine in PBDL-treated rats. The concentration of tissue malondialdehyde decreased in the pancreas and remote organs of PBDL and L-cysteine administrated rats, and the concentration of glutathione increased more significantly than that of the model control group. However, L-cysteine administration reduced the severity of injury in remote organs but not in the pancreas in rats with NaTc-induced AP.

CONCLUSION

L-cysteine treatment attenuated multiple organ damage at an early stage of AP in rats and modulated the oxidant/antioxidant imbalance.

摘要

背景

急性胰腺炎(AP)可导致远隔器官衰竭;然而,关于胰胆管阻塞引起的 AP 的报道很少。本研究旨在探讨 L-半胱氨酸对胰胆管结扎(PBDL)后大鼠胰胆系统炎症和远隔器官损伤的影响。

方法

采用 5/0 丝线结扎大鼠胰胆管诱导 AP,将 60 只大鼠随机分为 4 组。A 组和 B 组为假手术组,分别经腹腔注射生理盐水或 L-半胱氨酸(10mg/kg)(每组 15 只);C 组和 D 组为 PBDL 组,分别经腹腔注射生理盐水或 L-半胱氨酸(10mg/kg)(每组 15 只)。术后 24 小时,观察各组大鼠胰腺和肺、肝、肠、肾等远隔器官的组织病理学变化,检测丙二醛(MDA)和谷胱甘肽(GSH)水平。采用全自动生化分析仪检测血尿素氮(BUN)、血浆淀粉酶(AMS)、丙氨酸氨基转移酶(ALT)和天门冬氨酸氨基转移酶(AST)水平。采用逆行胆胰管注射 3.5%牛磺胆酸钠(NaTc)的方法复制 AP 模型,观察 L-半胱氨酸对 AP 大鼠远隔器官损伤的影响。

结果

PBDL 后 24 小时,大鼠胰腺、肺、肝、肠和肾均出现不同程度的损伤,L-半胱氨酸处理后,大鼠肺、肝、肠损伤程度减轻,但胰腺和肾脏损伤无明显变化。PBDL 大鼠氧化应激也受 L-半胱氨酸影响,PBDL 及 L-半胱氨酸处理组大鼠胰腺和远隔器官组织 MDA 浓度降低,GSH 浓度升高,且明显高于模型对照组。然而,L-半胱氨酸可减轻 NaTc 诱导的 AP 大鼠远隔器官的损伤程度,但对胰腺无明显影响。

结论

L-半胱氨酸治疗可减轻 AP 大鼠早期多器官损伤,调节氧化应激/抗氧化失衡。

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