血必净注射液对急性胰腺炎小鼠p38MAPK信号通路的影响

Effects of Xuebijing Injection acute pancreatic by p38MAPK pathwaysin mouse model

关键词:  血必净注射液  急性胰腺炎  p38丝裂原活化蛋白激酶

Key words:  Xuebijing injection  acute pancreatitis  p38MAPK

摘要:

[目的]观察血净注射液对雨蛙素诱导的急性胰腺炎（AP）小鼠的影响，并探讨p38蛋白激酶（p38MAPK）在血必净治疗胰腺炎症中的作用。[方法]将健康雄性小鼠C57BL/6J随机分成3组（n=5）：正常对照组、雨蛙素诱导AP模型组、血必净注射液治疗组。模型组和治疗组均腹腔注射雨蛙素（50 μg/kg，每天5次，间隔1 h，注射3天），治疗组在每天注射第5次雨蛙素30 min后给予尾静脉注射血必净注射液（13 mL/kg）。在腹腔注射雨蛙素最后一次造模完成后24 h，摘眼球取血至动物死亡。苏木精-伊红染色（HE）观察胰腺组织病理学变化；检测血清淀粉酶；酶联免疫吸附测定法（ELISA）检测胰腺组织中单核细胞趋化蛋白-1（MCP-1）蛋白含量表达；Western blot检测MAPK信号通路中c-Jun氨基末端激酶（JNK），胞外信号调节激酶（ERK1/2）和p38相关蛋白的表达。[结果]雨蛙素诱导的AP模型组在注射第3天第5次雨蛙素造模结束24 h后，血清淀粉酶明显升高，胰腺组织中MCP-1含量显著增加，与对照组相比有统计学差异（P<0.05）；血必净治疗组血清淀粉酶、胰腺组织中MCP-1均较AP模型组明显降低，与模型组相比有具有统计学差异（P<0.05）。AP模型组在造模结束24 h后胰腺组织可见明显病理损伤，而血必净组治疗组病理损伤较轻。在正常对照组、AP模型组、血必净治疗组中胰腺组织MAPK信号通路中JNK，ERK1/2以及p-JNK，p-ERK1/2蛋白表达均未有明显差异（P>0.05）；与正常对照组相比AP模型组p38MAPK蛋白的表达明显上调，血必净治疗组与AP模型组相比p38MAPK蛋白的表达明显下调（P<0.05）。[结论]血必净注射液可能通过抑制AP小鼠胰腺组织中p38MAPK炎症信号通路的激活，从而达到AP的保护作用。

Abstract:

[Objective] This study aimed to investigate the XBJ injection treated caerulein-induced acute pancreatic by the p38MAPK pathways.[Methods] Fifteen normal healthy C57BL/6J male mice were randomly divided into 3 groups (n=5):normal control group, Caerulein-induced acute pancreatitis model group (acute pancreatitis, AP), Xuebijing injection therapy group (AP+Xuebijing therapy). Cerulean-induced acute pancreatitis model and Xuebijing injection therapy groups were intra-peritoneal injected with caerulein (50 μg/kg, 5 times per day, interval of 1 hour, total 3 days). In the Xuebijing injection therapy group, Xuebijing with dosage of 13 mL/kg was applied via tail intravenous at the last times injection of caerulein every day. The mice were killed at 24 h time point after the final caerulein injection. Blood samples were acquired to determine serum amylase; Morphological changes of pancreas tissue were observed by Hematoxylin-Eosin staining; the expression level of MCP-1 in the pancreas tissues were detected by using ELISA; some of the crucial protein in the MAPK signal pathway, namely:JNK,ERK1/2 and p38 were analyzed by Western blot analysis.[Results] Xuebijing injection therapy achieved significant benefits for mouse model of Caerulein-induced acute pancreatitis. Morphological, Xuebijing injection therapy ameliorates the histological damage of Caerulein-induced pancreatic inflammation in the pancreas. Comparison with Caerulein-induced pancreatitic injury, Treatment with Xuebijing injection down-regulate the serum level of amylase (P<0.05), and the level of the most important chemokine MCP-1 (P<0.05), respectively. In addition, Xuebijing injection therapy inhibited the Caerulein induced activation of p38MAPK significantly (P<0.05).[Conclusion] Xuebijing injection may inhibitit the activity of p38MAPKsignaling pathway to protect the acute pancreatitis in mouse.