一氧化碳释放分子-2对大鼠急性坏死性胰腺炎的影响

Effect of carbon monoxide releasing molecule-2 （CORM-2） on rats with acute necrotizing pancreatitis

目的探讨一氧化碳释放分子-2（CORM-2）对大鼠急性坏死性胰腺炎（ANP）的影响。方法30只雄性Wistar大鼠按随机表法分为假手术（SO）组、ANP组和CORM-2组，每组10只。采用胆胰管逆行注入3．5％牛磺胆酸钠（1ml/kg体重）建立ANP模型。CORM-2组于ANP造模0．5h后经阴茎背动脉注射CORM-2（8mg／kg体重）。造模6h后处死动物，测定血清淀粉酶、脂肪酶、TNF-α、IL-1和IL-10含量；检测胰腺髓过氧化物酶（MPO）、丙二醛（MDA）活性及湿／干重比；对胰腺组织进行病理学评分。结果CORM．2组血清淀粉酶、脂肪酶、TNF—α、IL-1水平及胰腺病理学评分、组织MPO、MDA活性、湿／干重比分别为（5992±261）U／L、（407．6±87．2）U／L、（189．3±39．4）μg/L、（355．0±46．6）μg/L、18．4±3．5、（5．5±1．3）U／g、（24．6±6．7）nmol/mg prot、2．8±0．7，均显著低于ANP组的（7484±460）U／L、（537．9±102．6）U／L、（269．8±32．6）μg/L、（441．2±36．9）μg／L、24．9±4．6、（8．7±1．5）U／g、（41．6±5．1）nmol/mg prot、4，9±0．5（P〈0．05），而CORM-2组血清IL-10水平为（81．9±18．8）μg/L，显著高于ANP组的（52．3±14．8）μg/L（P〈0．05）。结论ANP时，应用CORM-2能够抑制系统炎症反应，减轻胰腺病理损伤，其机制可能与抑制促炎细胞因子TNF-α、IL-1的释放及上调抗炎细胞因子IL-10有关。

Objective To investigate the effect of carbon monoxide releasing molecule （CORM-2） on acute necrotizing pancreatitis （ANP） in rats. Methods Thirty male Wistar rats were randomly divided into three groups （n = 10 in each group）, including Sham Operation （SO） group, ANP group and CORM-2 group. ANP were induced by retrograde injection of 4% sodium taurocholate into the biliopancreatic duct. CORM-2 （8 mg/kg） was infused through the dorsal artery of penis 0.5 hour after establishing the model of ANP in CORM- 2 group. The rats were sacrificed six hours after ANP. The serum levels of amylase, lipase, tumor necrosis factor-α （TNF-α）, interleukin-1 （IL-1） and interleukin-10 （IL-10）, as well as the activity of myeloperoxidase （MPO） and maleic dialdehyde （MDA） in the pancreatic tissue were examined in each group. The wet/dry ratio of the pancreatic tissue was also determined. The pancreas was scored according to pathological changes. Results The serum levels of amylase, lipase, TNF-α, IL-1 and pathological score, MPO, MDA, wet/dry ratio in CORM-2 group were （5 992 ± 261 ） U/L, （407.6 ± 87.2） U/L, （ 189.3 ± 39.4）μg/L, （355.0 ±46.6）μg/L, 18.4 ±3.5, （5.5 ± 1.3）U/g, （24.6 ±6.7）nmol/mg prot, 2.8 ±0.7, which were significantly lower than those in the ANP group （ 7484 ± 460 ） U/L, （ 537.9 ± 102.6 ） U/L,（269.8 ±32.6） μg/L, （441.2 ±36.9） μg/L, 24.9 ±4.6, （8.7 ± 1.5）U/g, （41.6 ±5.1）nmol/mg prot, 4.9 ± 0.5 （P 〈 0.05 ）. The IL-10 level in CORM-2 group was （ 81.9 ± 18.8 ） μg/L, which were significantly higher than that in the ANP group （52.3 ± 14.8 ） μg/L （ P 〈 0.05 ）. Conclusions In ANP, administration of CORM-2 could remarkably inhibit the systemic inflammatory reaction and attenuate the severity of pancreatic injury, and the mechanism may include inhibit the release of TNF-α and IL-1 as well as up-regulate the production of IL-10.