摘要
目的：探讨慢性胰腺炎大鼠胰腺外分泌和胃窦运功功能的变化及中药柴胡疏肝散的干预作用。方法：健康Wistar大鼠50只,随机分为对照组、模型组、中药组、胰酶组和瑞健组,每组10只。模型组大鼠在无菌条件下打开腹腔,经肠壁逆行胰胆管插管,用注射泵以恒定的压力和速度向胆胰管内注射油酸的方法制备慢性胰腺炎模型,造模时间为6周。造模成功后,对照组及模型组大鼠每日予生理盐水灌胃,中药组大鼠每日予10g/100ml柴胡疏肝散溶液2ml/100g灌胃治疗；胰酶组大鼠予7.8mg/ml的得每通2ml／100g灌胃治疗,每日一次；瑞健组大鼠予1.5mg/ml瑞健2ml/100g灌胃,每日一次,共2周。8周后,分别检测各组粪脂肪滴计数、粪弹力蛋白酶1 (fecal elastase-1, FE-1)和各组血清胆囊收缩素(cholecystokinin, CCK)水平；观测胃窦环行平滑肌肌条收缩能力、环行平滑肌细胞收缩反应的变化；测定胃肌层诱导型一氧化氮合酶(inducible nitric oxide synthase, iNOS) mRNA的表达量和平滑肌细胞培养基中一氧化氮(Nitric Oxide, NO)含量的变化。结果：与对照组比较,模型组大鼠粪脂肪滴个数明显增加、FE-1水平明显降低,胃窦环行平滑肌条收缩能力、环行平滑肌细胞收缩反应明显下降(P<0.05),血清CCK水平,iNOS mRNA的表达量,细胞培养基中NO含量均明显升高(P＜0.05)；中药组和胰酶组大鼠均比模型组大鼠的粪脂滴个数明显减少、FE-1水平明显增高(P<0.05),中药组、胰酶组和瑞健组与模型组相比,胃窦环行平滑肌条收缩能力、环行平滑肌细胞收缩反应增加,血清CCK水平,iNOS mRNA的表达量,细胞培养基中NO含量均明显降低(P<0.05),以中药组效果最为明显。结论：慢性胰腺炎大鼠胰腺外分泌功能不全可导致CCK分泌增加,而CCK通过上调胃窦肌层iNOS mRNA的表达并产生过量的NO,抑制胃窦环行平滑肌的收缩能力可能是慢性胰腺炎胃运动功能障碍的机制之一；而中药柴胡疏肝散可以通过抑制CCK释放,下调肌层iNOS mRNA的表达并降低NO产量,从而有效的改善胰腺外分泌功能不全所致的胃动力障碍。
Objective:To explore the changes of exocrine pancreas in the rats with chronic pancreatitis combined exocrine pancreatic insufficiency and the intervention effect of the traditional Chinese drug.
Methods:Fifty Wistar rats were divided into control, model, traditional Chinese drug, trypsogen and Trimebutine Maleate Capsules group randomly(n=10). Rats in model group were used to induce chronic pancreatitis by injecting oleic acid into the pancreatic duct. The control and model groups, administered intragastrically with physiological saline everyday. The traditional Chinese drug group, administered intragastrically with 0.56g/ml Chaihu shugan san physiological saline 2ml/100g everyday; the trypsogen group, administered intragastrically with 7.8mg/ml Pancreatin Capsules 2ml/100g everyday; the Trimebutine Maleate group, administered intragastrically with 1.5mg/ml Trimebutine Maleate 2ml/100g everyday. The experiment period of each group are twe weeks. Eight weeks later, spot fecal fat and fecal elastase-1(FE-1) were detected, Serum cholecystokinin(CCK) was detected. Contractility of gastric circular muscle stripe and the contractile response of dispersed gastric circular smooth muscle cells stimulated by Aceylcholine (Ach) were measured. RT-PCR was used to detect the expression of inducible nitric oxide synthase (iNOS), mRNA within sinus ventriculi muscularis, the level of nitric oxide (NO) in cell cultures was quantified. Results:The counts of fecal fat in model group increased, level of FE-1 decreased obviously than that in control group. The gastric circular smooth muscle stripes contractility and contractile response of dispersed circular smooth muscle cells stimulated by Ach were declined obviously than the control (P<0.05) while the levels of serum CCK, iNOS mRNA expression and NO production were significantly elevated (P<0.05). Compared with the model group, the counts of fecal fat in traditional Chinese drug and trypsogen groups were less, and level of FE-1 higher (P<0.05), gastric circular smooth muscle stripes contractility and contractile response of dispersed circular smooth muscle cells stimulated by Ach in traditional Chinese drug, trypsogen and Trimebutine Maleate Capsules groups were elevated obviously than the model group, while the levels of serum CCK, iNOS mRNA expression and NO production were significantly declined (P<0.05), especially in the traditional Chinese drug group.
Conclusions:Elevated CCK secretion caused by insufficiency of pancreatic exocrine up-regulated the expression of iNOS mRNA and increased the output of NO within the gastric muscularis. It might be one of the mechanisms of gastric motility dysfunction in chronic pancreatitis that NO inhibited the contractility of gastric circular smooth muscle. The traditional Chinese drug(Chaihu shugan san) can improve the gastric motility dysfunction caused by exocrine pancreatic insufficiency efficiently, by inhibiting the release of CCK.
引文
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