海风藤酮对重症急性胰腺炎大鼠腹腔器官血流的干预效应(英文)

Interventional effect of kadsurenone on the splanchnic blood flow in rats with severe acute pancreatitis

背景:海风藤酮具有显著的抗氧化作用和钙离子拮抗样效应,能有效清除氧自由基,抑制钙离子内流,还能降低胰腺酶活性,减轻胰腺组织自我消化。目的:研究海风藤酮对重症急性胰腺炎大鼠腹腔器官血流,特别是胰腺血流的影响及其作用机制。设计:对比观察的动物实验。单位:解放军第四军医大学唐都医院普外科实验室和中心实验室。材料:选用Sprague-Dawiey(SD)雄性大鼠40只,清洁级,体质量200～280g。海风藤酮(共150mg)(北京大学药学院,批号:20050347);牛磺胆酸钠(Sigma公司,批号:86339);淀粉酶试剂(Roche公司,批号:irp170505)按说明书用。Imexlab9100多普勒超声诊断仪(美国Imex公司);多普勒超声诊断仪专用的8mHz探头(产品号X1-M008)(美国Imex公司)。方法:实验于2006-04/10在解放军第四军医大学唐都医院普外科实验室完成。应用随机数字表法选取8只大鼠作为假手术组,其余大鼠禁食12h后制作重症急性胰腺炎模型。造模后的重症急性胰腺炎大鼠采用随机数字表法分为2组:海风藤酮组(n=16)和模型组(n=16),两组又分别分为术后12和24h2个时间点进行观察,每个时间点8只。假手术组大鼠不进行任何手术操作。海风藤酮组大鼠术后3h经空肠造瘘管给药,剂量为海风藤酮10mg/kg,1次/6h,1～2次。配置时,药物溶于25g/L二甲基亚砜中,即刻应用。模型组大鼠经空肠造瘘管给予等量的二甲基亚砜。假手术组动物仅作开腹手术。假手术组于术后12h,模型组和海风藤酮组分别于重症急性胰腺炎术后12,24h测定血淀粉,同时运用多普勒超声测定胰腺局部动脉(相当于胰头、体交界处)、门静脉血流、脾动脉及肠系膜上动脉血流。主要观察指标:各组不同时间血浆淀粉酶和血流量变化情况。结果:纳入SD大鼠40只全部进入结果分析。①血浆淀粉酶测定结果:模型组和海风藤酮组血浆淀粉酶在各时点与假手术组相比均明显升高(P<0.01);模型组随时间延长,血浆淀粉酶继续升高,与术后12h比较,差异明显(P<0.05)。②胰腺局部动脉血流情况:在术后12和24h时,海风藤酮组和模型组胰腺局部动脉血流量明显低于假手术组(P<0.01);在海风藤酮组,随胰腺炎病程进展,胰腺局部血流量进一步下降(P<0.05),但各时点局部动脉血流量明显高于模型组(P<0.01)。③肠系膜上动脉根部、门静脉及脾动脉血流情况:海风藤酮组和模型组在术后12和24h时肠系膜上动脉血流量明显低于假手术组(P<0.01)。海风藤酮组各时点血流量与模型组比较,明显升高(P<0.01)。结论:海风藤酮能促使重症急性胰腺炎大鼠胰腺血流量增加,减轻胰腺的病理损害。

BACKGROUND： Kadsurenone is characterized by obvious anti-oxidation and calcium ion resistant effect and can effectively clear oxygen-derived free radicals, decrease activity of pancreatic enzyme, and relieve self-digestion of pancreatic tissue. OBJECTIVE： To observe the effects of kadsurenone on the splanchnic blood flow in rats with severe acute pancreatitis （SAP）, especially the mechanism of pancreatic blood flow. DESIGN： Contrast observational animal study.SETTING：Laboratory of General Surgery and Central Laboratory of Tangdu Hospital, the Fourth Military Medical University of Chinese PLA. MATERIALS： A total of 40 male Sprague-Dawiey （SD） rats, of clean grade and weighing 200-280 g, were selected in this study. Kadsurenone （150 mg） was provided by Pharmacological College of Peking University （batch number： 20050347）; sodium taurocholate by Sigma Company （batch number： 86339）; amylase reagent by Roche Company （batch number： irp 170505）; Imexlab9100 Doppler ultrasound diagnostic meter by Imex Company; 8 mHz probe privated by Doppler ultrasound diagnostic meter by Imex Company, USA （number： X1-M0008）. METHODS： The experiment was carried out in the Laboratory of General Surgery, Tangdu Hospital, Fourth Military Medical University of Chinese PLA from April to October 2006. Eight rats were randomly selected as sham operation group, and other rats were used to establish SAP models at 12 hours after fasting. Continuously, 32 SAP rats were randomly divided into two subgroups after model establishment, including kadsurenone group （n =16） and model group （n =16）. In addition, all rats in the two subgroups were observed at 12 and 24 hours after operation with 8 rats at each time point. However, rats in the sham operation group did not give any treatment. At 3 hours after operation, rats in kadsurenone group were given 10 mg/kg kadsurenone through jejunum fistula once every 6 hours for one or two times in total. Kadsurenone was dissolved in 25 g/L dimethyl sulfoxide. In addition, rats in model group were given the same dosage of dimethyl sulfoxide through jejunum fistula; furthermore, rats in sham operation group were only opened their abdomens. Blood starch was respectively measured in sham operation group at 12 hours after abdominal operation, model group at 12 hours and kadsurenone group at 24 hours after acute pancreatic operation; meanwhile, Doppler ultrasound was used to detect local artery of pancreas （relative to the crossed site between head and body of pancreas）, blood flow of portal vein, splenic artery and blood flow of superior mesenteric artery. MAIN OUTCOME MEASURES： Changes of plasma amylase and blood flow at various time points.RESULTS ： All 40 SD rats were involved in the final analysis.①Measuring results of plasma amylase： Level of plasma amylase was increased in both model group and kadsurenone group at various time points as compared with that in sham operation group （P〈0.01 ）. With the time passing by, level of plasma amylase was still increased in model group, and there was significant difference from that at 12 hours after operation （P〈0.05）. ②Blood flow of local pancreatic artery： At 12 and 24 hours after operation, blood flow was lower in kadsurenone group and model group than that in sham operation group （P〈0.01）. With the development of illness course, blood flow was still decreased in kadsurenone group （P〈0.05）; however, blood flow was obviously higher than that in model group at various time points （P〈0.01 ）. ③ Blood flow of superior mesenteric arterial root, portal vein and splenic artery： Blood flow was lower in kadsurenone group and model group than that in sham operation group at 12 and 24 hours after operation, respectively （P〈0.01）. In addition, blood flow was remarkably increased in kadsurenone group as compared with that in model group at various time points （P〈0.01）. CONCLUSION： Kadsurenone can increase the pancreatic blood flow and relieve pathological injury in SAP rats.