姜黄素对大鼠重症急性胰腺炎炎症反应的影响及其机制研究

Effect of curcumin on the inflammatory response in rats with severe acute pancreatitis and the underlying mechanisms

摘要:

目的 探究姜黄素对大鼠重症急性胰腺炎（SAP）炎症反应的影响，并分析可能的作用机制。方法 将50只SPF级SD大鼠随机分为假手术组、SAP模型组、姜黄素低剂量组、姜黄素高剂量组、阳性对照组，每组10只。除假手术组（大鼠仅翻动十二指肠、胰腺，不穿刺注药，其余操作同模型组）外，SAP模型组、姜黄素低剂量组、姜黄素高剂量组、阳性对照组均复制SAP模型。模型复制过程中SAP模型组、姜黄素低剂量组大鼠各死亡1只。模型复制成功后，姜黄素低、高剂量组大鼠即刻腹腔注射姜黄素50 mg/kg、200 mg/kg，阳性对照组腹腔注射2 mg/kg地塞米松，假手术组、SAP模型组大鼠腹腔注射等量生理盐水，以上药物处理均连续3 d。药物干预结束后，测定各组大鼠腹水量；采用全自动生化分析仪测定大鼠血清淀粉酶（Amy）水平；酶联免疫吸附试验测定血清白细胞介素6（IL-6）、肿瘤坏死因子-α（TNF-α）水平；苏木精-伊红（HE）染色观察各组大鼠胰腺组织病理学变化并进行病理学评分；Western blotting检测各组大鼠胰腺组织JAK2/STAT3通路蛋白的表达。结果 与假手术组比较，SAP模型组、姜黄素低、高剂量组及阳性对照组大鼠腹水量，血清Amy、IL-6、TNF-α水平，组织病理学评分及p-JAK2/JAK2、p-STAT3/STAT3蛋白相对表达量升高（P <0.05）；姜黄素低、高剂量组及阳性对照组大鼠腹水量，血清Amy、IL-6、TNF-α水平，组织病理学评分及p-JAK2/JAK2、p-STAT3/STAT3蛋白相对表达量低于SAP模型组（P <0.05）；姜黄素高剂量组及阳性对照组腹水量，血清Amy、IL-6、TNF-α水平，组织病理学评分及p-JAK2/JAK2、p-STAT3/STAT3蛋白相对表达量低于姜黄素低剂量组（P <0.05）。结论 姜黄素可能通过抑制JAK2/STAT3通路活化抑制炎症反应，进而对SAP大鼠胰腺损伤发挥保护作用。

Abstract:

Objective To explore the effect of curcumin on the inflammatory response in severe acute pancreatitis (SAP) and to analyze the possible mechanisms.Methods Specific-pathogen free (SPF) SD rats were randomly divided into sham operation group, SAP model group, low-dose and high-dose curcumin group, and positive control group. Except for the sham operation group (n = 10), where the duodenum and pancreas of rats were not punctured and injected with drugs, SAP model group (n = 9), low-dose curcumin group (n = 9), high-dose curcumin group (n = 10) and positive control group (n = 10) were all established as SAP models. Following the modeling, rats in low- and high-dose curcumin groups were treated with 50 mg/kg and 200 mg/kg of curcumin intraperitoneally, rats in positive control group were injected with 2 mg/kg of dexamethasone intraperitoneally, and rats in sham operation group and SAP model group were injected with an equal volume of normal saline intraperitoneally. The treatments continued for 3 days in all groups. After the drug intervention, the volume of ascites in rats of each group was measured. The level of serum amylase (Amy) was detected via automatic biochemical analyzer, while the serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were detected via enzyme-linked immunosorbent assay (ELISA). The histopathological changes of pancreatic tissues in each group were observed and scored via hematoxylin and eosin (HE) staining. The expressions of proteins associated with the Janus kinase 2 / signal transducer and activator of transcription 3 (JAK2 / STAT3) pathway in pancreatic tissues were detected via Western blotting.Results Compared with the sham operation group, the volume of ascites, the serum levels of Amy, IL-6 and TNF-α, the histopathological scores, and the protein expressions of p-JAK2/JAK2 and p-STAT3/STAT3 were increased in SAP model group, low- and high-dose curcumin groups, and positive control group (P < 0.05). However, the volume of ascites, the serum levels of Amy, IL-6 and TNF- α, the histopathological scores, and the protein expressions of p-JAK2 / JAK2 and p-STAT3/STAT3 were lower in the low- and high-dose curcumin groups and positive control group than those in the SAP model group (P < 0.05). In addition, these indicators were even lower in the high-dose curcumin group and the positive control group relative to those in the low-dose curcumin group (P < 0.05).Conclusions Curcumin may inhibit the inflammatory response by suppressing the activation of JAK2/STAT3 pathway, thereby playing a protective role in the pancreatic injury in SAP rats.