【作者】 王惠；

【导师】 唐文富；

【作者基本信息】 成都中医药大学 ， 中西医结合临床， 2013， 硕士

【摘要】 目的：观察基于主观饥饿感的轻症急性胰腺炎(MAP)患者早期再进食的安全性和临床效果。方法：采用随机对照实验方法,将2011.1-2011.12四川大学华西医院中西医结合科收治的149例急性轻症胰腺炎患者,随机分成早期再进食组(75例)和对照组(74例),早期进食组以患者有主观饥饿感为进食时机,而对照组的进食时间为患者腹部柔软,腹痛、腹胀明显缓解,血清淀粉酶恢复至正常上限2倍以下。对比分析两组患者腹痛发作到再进食的平均时间、再进食后腹痛复发或加重的病例数、腹胀加重病例数、进食前后血糖变化、酶学升高例数、总住院时间、再进食后住院时间的差异。结果：早期再进食组和对照组腹痛发作到再进食时间分别是4.56±1.53d和6.75±2.29d(p<0.05),具有统计学意义；两组的总住院时间分别是6.8±2.1d和10.4±4.1d(p<0.01),具有统计学意义；两组再进食后住院时间分别为2.24±0.52d和3.27±0.61d(p<0.01),具有统计学意义；早期再进食组再进食后平均血糖水平低于再进食前(p<0.01),具有统计学意义。两组性别、年龄、腹痛复发或加重的病例数、腹胀加重的病例数无统计学差异(p>0.05)。两组都没有发现因再进食而出现明显胃肠道副作用,也没有患者因此中止再进食。结论：基于主观饥饿感的轻症急性胰腺炎患者早期再进食是安全的,它能缩短AP患者的住院时间,有利于血糖控制。目的：1、研究熟大黄(五种主要单体)在急性胰腺炎状态下是否有靶向组织分布特点；2、熟大黄能否通过增加TGF-β1以促进急性胰腺炎大鼠胰腺组织再生。方法：①熟大黄靶向分布的药动学研究：雄性SD大鼠10只随机分为正常组和模型组,每组5只,正常组不做任何处理,模型组采用腹腔内注射蛙皮素(50μg/kg)制备急性胰腺炎(acute pancreatitis, AP)模型。所有大鼠予次日早上9：00给予熟大黄生药12g/kg的等量颗粒剂剂量灌胃给药1次,给药后2小时用10%水合氯醛溶液腹腔注射麻醉全部大鼠,腹主动脉抽血,取肝、心、脾、肺、肾、胰腺等6个组织,液相色谱-质谱／质谱(HPLC-MS/MS)法分析熟大黄一次给药后5种主要蒽醌成分：大黄素、大黄酸、大黄酚、芦荟大黄素、大黄素甲醚在大鼠心、肝、脾、肺、肾、胰腺的组织分布。②促再生的药效学研究：雄性SD大鼠60只随机分为假手术组、模型组、低剂量组、中剂量组和高剂量组,每组12只,其中48只采用腹腔内注射蛙皮素(50μg/kg)制备急性水肿型胰腺炎模型,12只为假手术组。三种不同剂量熟大黄灌胃,第2、5、8天分批用10%水合氯醛溶液腹腔注射麻醉、腹主动脉抽血,取胰腺组织,用比色法检测大鼠血清淀粉酶AMY,观察胰腺组织病理积分,检测再生指标TGF-β1的不同时点免疫组化,并用激光多普勒血流仪检测活体的胰腺组织血流灌注量。结果：(1)药动学部分：①熟大黄5种成分在正常大鼠胰腺组织内浓度分布并不高于其他几个器官。而在胰腺炎模型中,大黄素、大黄酸显示出对胰腺的靶向性亲和力,其胰内浓度均高于其他器官。②急性胰腺炎大鼠胰腺组织内熟大黄成分大黄素、大黄酸的浓度高于正常大鼠胰腺；急性胰腺炎大鼠肾组织内大黄素浓度高于正常大鼠,脾组织内大黄酸、大黄素甲醚浓度高于正常大鼠；熟大黄其余成分在两组大鼠的各组织内的浓度没有统计学差异。(2)药效学部分：熟大黄能降低胰腺炎大鼠血清淀粉酶、胰腺组织病理学评分,使细胞外基质中的TGF-β1表达增加,胰腺炎后活体大鼠胰腺组织血流灌注量增加。结论：(1)本研究初步证明熟大黄可能通过TGF-β1促进胰腺炎大鼠胰腺组织再生；(2)胰腺组织为胰腺炎病理证候下的药物作用靶器官,初步证实了熟大黄促再生的组织靶向性；(3)初步筛选出熟大黄促进胰腺组织再生的靶向性药效物质可能是大黄素,大黄酸；(4)从治疗学角度为中药归经理论提供了一定的科学依据。更多还原

【Abstract】 To observe the safety and the clinical efficacy of early oral refeeding based on subjective sensation of hunger in patients with mild acute pancreatitis.Methods:One hundred and forty-nine patients with mild acute pancreatitis admitted in Pancreatic Research Group, Department of Integrated Traditional and Western Medicine at West China hospital, Sichuan,from January2011to December2011were enrolled and divided into early oral refeeding group and control group randomly.Patients for early oral refeeding group restarted oral refeeding when they felt hungry,while the control group restarted when the patient’s abdominal distension and abdominal pain were significantly relieved, and the serum amylase recovered to less than2times the upper limit of normal.The difference as the average days of oral refeeding after abdominal pain onset, number of patients with pain relapse or transitional abdominal distension after oral refeeding, number of patients with amylase and lipase became more higher, number of patients with glycemic change after oral refeeding, and the length of hospital stay (LOH) for total and post-refeeding in two groups were compared.Results:The average days of oral refeeding after abdominal pain onset were4.56±1.53days for early refeeding group and6.75±2.29days for control group (p<0.05);The LOH for total between the two groups were statistically different with6.8±2.1days and10.4±4.1days,respectively (p<0.01).;The LOH for post-refeeding were2.24±0.52days and3.27±0.61days (p<0.01). The mean level of blood glucose after oral refeeding in early refeeding group was lower than that before oral refeeding (p<0.01),which was statistically difference.There was no statistically difference in age, sex, number of patients with pain relapse or transitional abdominal distension after oral refeeding in two groups (p>0.05). There were no serious adverse events observed after oral refeeding during the study and there were no patients interrupting oral refeeding in both groups.Conclusion:Early oral refeeding based on the subjective hunger feeling is safe and effective in patients with mild acute pancreatitis,which could help to shorten the LOH and is beneficial for the blood glucose control. (1) To explore the targeting tissue distribution characteristics of the prepared rhubarb (five main monomers)in rats with acute pancreatitis(AP);(2)To identify the potential mechanism of the prepared rhubarb in promoting the regeneration of rat pancreatic tissue by increasing TGF-β1.Methods:(1) Pharmacokinetic study about targeted distribution of the prepared rhubarb:Ten male SD rats were divided into normal group and model group. There were no processes with the normal group, while the model group was given intraperitoneal injection with caerulin (50μg/kg) seven times to produce AP model. Rats in both groups were given same dose of prepared rhubarb granules (12g/kg) once by gavage at9:00the next morning,2hours later then, all rats were anesthetized by giving intraperitoneal injection with chloral hydrate (10%). We analyzed the tissue distribution of five main anthraquinone (Emodin, rhein, chrysophanol, aloe-emodin, emodin-Ether) in heart, liver, spleen, lung, kidney, pancreas with HPLC-MS/MS.(2) Pharmacodynamic study about the promotion of the regeneration:Sixty male SD rats were randomly divided into sham operation group, model group, low-dose group, middle dose group and high dose group, with12rats in each group. Of all the rats,48were given intraperitoneal injection with caerulin (50μg/kg) to produce AP model,12were given intraperitoneal injection with physiological saline. After giving three different dose of prepared rhubarb, we drew blood from abdominal aortic respectively in2,5,8days and got pancreas tissue. Blood Serum amylase, the pancreatic histopathology, the expression of TGF-β1in pancreas at various points and the biopsy blood perfusion in pancreas of live rats (with Laser Doppler Flowmetry) were detected. Results:(1)Pharmacokinetic section:①The five main components of prepared rhubarb in pancreas were not higher than in other organs in normal group. However, in AP model group.we found higher concentrations of emodin and rhein in pancreas, which implied these two components targeted pancreas rather than the other organs.②The concentrations of emodin and rhein from prepared rhubarb in pancreas of rats with AP were higher than those in the pancreas of normal rats. The concentration of emodin in kidney of rats with AP is higher than that in the normal rats. The concentrations of rhein and emodin in spleen with AP is higher than that in the normal rats. The concentrations of other components of prepared rhubarb showed no statistically difference in two groups.(2) Pharmacodynamic section:Prepared Rhubarb helps to decrease the blood amylase and histopathology lever of pancreas, increase the blood perfusion in the pancreas of live rats and promoted the expression of TGF-β1in extracellular matrix of pancreas.Conclusion:(1)This study proved that prepared rhubarb could promote the pancreatic regeneration in rats with AP through TGF-β1;(2) It was preliminarily confirmed that the prepared rhubarb could promote pancreatic regeneration with tissue targeted distribution of its components.(3) Emodin and rhein were the potential targeted pharmacodynamic materials in the course of pancreatic regeneration;(4) The study provided a scientific basis for clarifying the meridian tropism theory of Chinese herb from the perspective of therapy.更多还原