氯化钆对大鼠急性出血坏死性胰腺炎肺损伤的影响

Effects of gadolinium chloride on acute hemorrhagic necrotizing pancreatitis associated lung injury in rats

目的 观察氯化钆对大鼠急性出血坏死性胰腺炎 (AHNP )肺损伤的影响 ,探讨肝脏Kupffer细胞在该病理过程中的作用。方法 42只Wistar大鼠随机分为假手术组、模型组、氯化钆预防组( 10mg/kg)、氯化钆对照组 ( 10mg/kg)。假手术组仅翻动腹腔脏器数次即关腹 ;模型组经胆胰管逆行注射 5 %牛磺胆酸钠 ( 1ml/kg ,0 .1ml/min)诱发AHNP ;氯化钆预防组在AHNP造模前 1d经尾静脉注射氯化钆溶液。 3组动物于术后 3h ,6h分批取材 :( 1)经腹主动脉取血 ,测定血清淀粉酶、TNFα和IL 1(假手术组加测血AST和ALT) ;( 2 )取右肺一部分匀浆 ,测定MPO ;另一部分经 10 %甲醛固定 ,行组织病理学观察 ;( 3 )取左肺进行肺泡灌洗 ,分离收集并纯化肺泡巨噬细胞 ;提取核蛋白后采用化学发光ELISA法检测NF κB (p65 )的表达情况 ;( 4 )留取胰腺组织行组织病理学观察。氯化钆对照组经尾静脉注射氯化钆溶液 2 4h后处死 ,取血测定血AST和ALT。结果 氯化钆预防组在造模后 3h及 6h ,肺组织MPO水平、血清TNFα及IL 1水平、肺泡巨噬细胞NF κB(p65 )的表达水平均显著低于模型组 (均为P <0 .0 1) ;肺组织病理学改变显著减轻。血清淀粉酶及胰腺病理改变两组无显著差别。结论 预防性应用氯化钆可明显减轻AHNP大鼠所并发的肺损伤 ;

Objective To investigate the role of hepatic Kupffer cells in acute hemorrhagic necrotizing pancreatitis associated lung injury(AHNP LI) and the therapeutic effects of gadolinium chloride(GdcI_3). Methods Forty-two Wistar rats were randomly divided into four groups:(I) sham operation group;(II) AHNP group;(III) Gdcl_3 (protection) group(Gdcl3 10mg/kg);(IV) Gdcl_3control group(Gdcl_3 10mg/kg).In the sham operation group, the (abdominal) vescera were shifted around for several times and the abdomen was closed.The AHNP model was induced by retrograde intraductal administration of 5% sodium taurcholate(1ml/kg,0.1ml/min).In the Gdcl_3 protection group,Gdcl_3 solution was admmistered by caudal vein injection one day before the AHNP model was made.In these 3 group of animals,specimens were obtained in order at 3h and 6h postoperatively:(1)Blood was withdrawn from the abdominal aorta to determine serum amylase,TNFα,IL-1(in addition,in the sham operation group,blood AST and ALT were determined);(2)A portion of liguefied right lung was obtained to determine MPO;another portion was fixed with 10% formalin for tissue pathological examination;(3)Bronchoalveolar lavage fluid of excised left lung was obtained ,and then alveolar macrophages were isolated,collected and purified.After removal of their nuclear (proteins),the alveolar macrophages were tested to determine NF-κB activation with the use of chemical illumination ELISA method;and (4)pancreatic tissue was reserved for pathological examination.In the Gdcl_3 control group, Gdcl_3 was administered by caudal vein injection,the animals were sacrificed 24h later,and blood was obtained to determine blood AST and ALT. Results In the Gdcl_3 prevention group,the level of MPO in lung tissue,serum (levels) of TNPα and IL-1,and NF-κB activation of alveolar (macrophages) were all significanfly reduced as compared with the AHNP model group(in all,P<0.01),and the pathological injury of the lung was significantly reduced.The level of blood amylase and the degree of pathological injury of the pancreas showed no significant change. (Conclusions) The preventative use of Gdcl_3 can significantly ameliorate AHNP LI in rats.Hepatic kupffer cells play a vital role in AHNP LI.