大承气汤治疗大鼠实验性急性胰腺炎肠功能障碍的机制研究

目的 探讨大承气汤治疗大鼠实验性急性胰腺炎(AP)肠功能障碍的可能机制.方法 将72只成年SD大鼠随机分为假手术组(SO组)、胰腺炎组(AP组)和大承气汤治疗组,每组24只.经胆胰管内加压注射3.5%牛磺胆酸钠0.1 ml/100 g体重制备AP模型,治疗组在造模前给予大承气汤按2 g/100 g体重剂量灌胃1次,AP组和SO组则灌注等量0.9%氯化钠溶液.每组于造模后3、6、12 h各处死8只大鼠并立即心脏取血,检测血清淀粉酶水平,酶联免疫吸附试验检测血清5-羟色胺(5-HT)含量.同时取6 h时间点各组大鼠距屈氏韧带10 cm空肠、末端回肠及乙状结肠组织,采用RT-PCR和Western印迹法检测肠黏膜中5-HT_3、5-HT_4mRNA及蛋白表达情况.结果 ①造模后AP组和治疗组血清淀粉酶、5-HT水平均明显高于SO组(P<0.01),且每个时间点治疗组均较AP组显著降低(P<0.05);AP组和治疗组5-HT水平均呈现出先升后降趋势.②与SO组相比,AP组5-HT_3、5-HT_4mRNA及蛋白表达水平在空肠、末端回肠及乙状结肠均明显下降(P<0.01);与AP组比较,治疗组各部位5-HT_4mRNA及蛋白表达均增高(P<0.05),而5-HT_3 mRNA 及蛋白表达则未增加.结论 5-HT升高及其受体降低可能是AP发生肠功能障碍的原因之一,而大承气汤治疗的主要作用可能是通过增加5-HT_4表达以改善肠功能,可作为AP肠功能障碍的治疗方法之一.

Effect of Da-Cheng-Qi decoction on enteric functional disturbance in rats with acute experimental pancreatitis and its mechanism

Objective To investigate the effect of Da-Cheng-Qi decoction on enteric functional disturbance in rats with acute experimental pancreatitis and its potential mechanism. Methods Seventy-two SD rats were randomly divided into sham operation group, acute pancreatitis (AP) group and Da-Cheng-Qi decoction treated group with 24 each. The AP model was induced by retrograde injection of sodium taurocholate (0.1 ml/100 g) into bitiopancreatic duet. Before modeling, the rats in treatment group received Da-Cheng-Qi decoction (2 g/100 g), and the rats in other two groups received 0.9% NaCl solution. The rats were sacrificed at 3, 6 and 12 hours with 8 each, and the blood samples were taken for detecting the level of amylase and the contents of 5-hydroxytryptamine (5-HT) by enzyme-linked immunosorbent assay. The colonic tissues 10 cm apart from trans-ligament incluing jejunum, terminal ileum and sigmoid colon were collected for examining the expressions of 5-HT_3 and 5-HT_4mRNA and proteins by RT-PCR and Western blotting respectively. Results ① The levels of serum amylase and 5-HT in AP group and treatment group were significantly higher than those in sham operation group (P<0. 01), but they were lower in treatment group than in AP group at each time points (P<0. 05). The level of 5-HT was increased in the initial stage and then decreased gradually both in AP group and treatment group. ③ The expressions of 5-HT_3 and 5-HT_4 mRNA and proteins were significantly decreased in the jejunum, terminal ileum and sigmoid colon in AP group compared with sham operation group (P<0. 01). Whereas the expressions of 5-HT_3 mRNA and protein,but not 5-HT_4, were increased in the treatment group in comparison with AP group (P<0.05). Conclusions The level of 5-HT is significantly increased in acute pancreatitis, but its receptors (5-HT_3 and 5-HT_4) are decreased, which may induce enteric functional disturbance. The Da-Cheng-Qi decoction may improve enteric dynamic failure by increasing the expression of 5-HT_4 and may be a choice for treatment of acute pancreatitis with enteric dynamic failure