胆碱能抗炎通路在大鼠胆肠吻合术后全身及吻合口炎症反应中的作用

Role of cholinergic anti-inflammatory pathway in systemic and local inflammation for bilioenteric anastomosis rat model

目的研究胆碱能抗炎通路在大鼠胆肠吻合术后全身及吻合口炎症反应中的作用。方法60只SD大鼠，随机分为10组，每组6只，包括正常组（一期术前组，二期术前组）、实验组（3天组，1周组，2周组，1月组）和对照组（3天组，1周组，2周组，1月组）。实验组大鼠术后第1天即开始给予胆碱能抗炎通路药物（山莨菪碱25mg／kg联合新斯的明50μg/kg）腹腔注射，连续7日；对照组给予等量的生理盐水。比较两组大鼠不同时间点机体应激指标以及胆管壁HE染色和TGF-β1免疫组化染色情况。结果顺利完成各组实验手术操作。（1）实验组大鼠在术后第3天、术后1周和术后2周的C反应蛋白（CRP）、TNF-α和IL-1β指标分别为（3．6±0．2）mg／L、（2．9±0．4）pg／ml、（126．9±19．0）pg／ml；（2．6±0．3）mg／L、（2．0±0．3）pg／ml、（73．4±8．6）pg／ml和（2．3±0．1）mg／L、（1．7±0．4）pg／ml、（53．2±6．5）pg／ml，均明显优于对照组大鼠（P〈0．05）。术后1个月两组各项指标差异无统计学意义（P〉0．05）。（2）实验组大鼠胆管壁的HE染色所示炎症细胞浸润情况在术后各个时间点均比对照组轻，TGF-β1表达也较对照组少。结论术后给予山莨菪碱和新斯的明双向活化胆碱能抗炎通路，能有效降低大鼠胆肠吻合术后全身及吻合口的炎症反应，有望为临床防治胆肠吻合术后吻合口炎症提供一种有效的治疗手段。

Objective To examine the effect of cholinergic anti-inflammatory pathway on systemic and bilioenteric anastomotic inflammatory after hilioenteric anastomosis in rats. Methods A total of 60 SD rats were randomly divided into 10 groups with 6 rats in each group, including 2 normal group （phase one group and phase two preoperative group）, 3 experimental group （3-days group, 1-week group, 2-weeks group and 1-month group） , and 3 control group （3-days group, l-week group, 2-weeks group and 1-month group）. The experimental groups received cholinergic anti-inflammatory pathway medication （25 mg/kg anisodamine combined with 50 μg/kg neostigmine） by intraperitoneal injection since the first day post operation for 7 days. The control group was given saline. The stress index, HE staining and TGF-β1 staining of the common bile duct were compared between the two groups at different time points. Results The operation of each group was successfully completed. The stress indexes of CRP, TNF-α and IL-1β in the experimental group in 3 days, 1 week and 2 weeks post operation were （3.6 ±0.2）mg/L, （2.9±0.4）pg/ml, （126.9 ±19. 0）pg/ml; （2.6 ±0. 3）mg/L, （2.0 ±0. 3）pg/ml, （73.4 ±8.6）pg/ml and （2.3 ±0. 1）mg/L, （ 1.7 ± 0. 4 ） pg/ml, （ 53.2 ± 6. 5 ） pg/ml, which were significantly better than those of the control group （P 〈 0. 05 ） but not significantly different in 1 month after operation （P 〉 0.05 ）. HE and TGF-β1 staining of common bile duct in the experimental group showed that the inflammatory reaction was decreased compared with that in the control group at each time point post operation. Conclusion Cholinergic anti-inflammatory pathway can effectively reduce the systemic and local inflammatory response in bilioenterie anastomosis rat model, which might provide an effective treatment in clinical practice.