中国普外基础与临床杂志

中国普外基础与临床杂志

巨噬细胞移动抑制因子抑制剂 ISO-1 在妊娠大鼠急性坏死性胰腺炎肠损伤中的作用

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目的 探讨巨噬细胞移动抑制因子(MIF)在妊娠大鼠急性坏死性胰腺炎(ANP)肠损伤中的作用。 方法 使用随机数字表法将 24 只妊娠 SD 大鼠(简称孕鼠)随机分为假手术组(SO 组)、急性坏死性胰腺炎组(ANP 组)及 MIF 抑制剂(S,R)-3-(4-羟苯基)-4,5-二氢-5-异噁唑乙酸甲酯(ISO-1)干预组(ISO-1 组)3 组,每组 8 只孕鼠。采用逆行胰胆管注射 5% 牛磺胆酸制备 ANP 模型,术后 12 h 剖杀孕鼠进行取材,取下腔静脉血检测血清淀粉酶(AMY)、脂肪酶(LIP)、二胺氧化酶(DAO)、白细胞介素(IL)-1β 及 IL-6 水平,取胰腺组织及空肠组织行病理学检查并评分,免疫组织化学方法检测肠道组织中 MIF、核因子(NF)-κB 及肿瘤坏死因子(TNF)-α 蛋白表达。 结果 ① 血清中 AMY、LIP、DAO、IL-1β 及 IL-6 水平在 ANP 组均明显高于 SO 组(P<0.05);与 ANP 组比较,ISO-1 组血清中 AMY、LIP 水平下降并不明显(P>0.05),而血清中 DAO、IL-6 和 IL-1β 水平均显著降低(P<0.05)。② 胰腺和肠道组织病理评分在 ANP 组均明显高于 SO 组(P<0.05),其在 ISO-1 组均明显低于 ANP 组(P<0.05)。③ MIF、NF-κB 及 TNF-α 蛋白表达的 IOD 值在 ANP 组孕鼠肠道组织中均明显高于 SO 组(P<0.05),其在 ISO-1 组孕鼠肠道组织中均明显低于 ANP 组(P<0.05)。 结论 MIF 抑制剂 ISO-1 对孕鼠 ANP 肠损伤具有一定的保护作用,其机制可能与抑制 NF-κB 及 TNF-α 的激活有关。

Objective To explore effects of macrophage migration inhibitory factor (MIF) inhibitor ISO-1 on intestinal injury in acute necrotic pancreatitis in pregnancy (ANPIP) rat. Methods Twenty-four pregnant Sprague-Dawley rats were randomly averagely divided into three groups: a sham operation (SO) group, an ANP group, and an ANP model plus ISO-1 treatment group (ISO-1 group). A rat model of ANP was induced by the retrograde injection of 5% sodium taurocholate into the biliopancreatic duct. The rats were killed and the inferior vena cava blood, and the tissues of pancreas and jejunum were harvested at 12 h after the operation. The serum amylase (AMY), lipase (LIP), diamine oxidase (DAO), interleukin (IL)-1β, and IL-6 levels were measured. The pancreatic and jejunal tissues were taken for the pathological examination scoring. The immunohistochemical method was used to detect the expression of the MIF, nuclear factor-kappa B (NF-κB), or tumor necrosis factor (TNF)-α protein. Results ① Compared with the SO group, the serum AMY, LIP, DAO, IL-1β, and IL-6 levels were increased in the ANP group (P<0.05), which in the ISO-1 group were decreased as compared with the ANP group, the DAO, IL-1β, and IL-6 levels had significant differences (P<0.05), but the AMY and LIP levels had no significant differences (P>0.05). ② The pathological points of the pancreas and jejunum tissues were increased in the ANP group as compared with the SO group, which were significantly decreased in the ISO-1 group as compared with the ANP group (P<0.05). ③ The average integrated optical density divide by area of NF-κB, TNF-α, and MIF were significantly increased in the ANP group as compared with the SO group, which were significantly decreased in the ISO-1 group as compared with the ANP group (P<0.05). Conclusions MIF inhibitor ISO-1 could protect intestinal injury in ANPIP rat. It is suggested that MIF is one of mechanisms in ANPIP with intestinal injury and might be correlated with activities of TNF-α and NF-κB.

关键词: 妊娠合并急性胰腺炎; 肠损伤; 巨噬细胞移动抑制因子; 核因子-κB; 肿瘤坏死因子-α

Key words: acute pancreatitis in pregnancy; intestinal injury; macrophage migration inhibitory factor; nuclear factor-κB; tumor necrosis factor-α

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