N-乙酰半胱氨酸改善重症急性胰腺炎胰腺微循环的研究

Study of N-acetylcysteine improving microcirculation with severe acute pancreatitis

目的:探讨N-乙酰半胱氨酸(NAC)对大鼠重症急性胰腺炎(SAP)微循环的改善作用。方法:取健康SD大鼠54只,雌雄各半,体质量200~250 g,随机分为正常对照组、SAP组和NAC治疗组各18只。应用3.5%的牛磺胆酸钠(0.1 mg/100g)通过逆行胰胆管注射建立大鼠SAP模型。NAC治疗组在制备大鼠SAP模型完成30 min后经腹腔给予100 mg/kg的NAC;正常对照组、SAP组大鼠腹腔注射等剂量的生理盐水。各组大鼠分别于造模成功后6 h、12 h、24 h分批处死,心脏取血检测大鼠血清中淀粉酶、血清白介素-6(IL-6)水平,检测胰腺组织血栓素B2(TXB2)、6-酮-前列腺素-F1a(6-Keto-PGF1α)含量,同时留取胰腺头颈部组织,观察病理学变化并进行病理学评分。结果:SAP组胰腺病理组织切片从6 h^24 h均可观察到胰腺组织水肿、白细胞浸润以及出血和坏死;在NAC治疗组出现相似的变化,但组织损伤明显减轻,水肿、白细胞浸润减少,出血及坏死显著减轻。NAC治疗组与SAP组比较,6 h时间点开始病理评分显著降低(P<0.05);12 h及24 h时间点进一步降低(P<0.05)。NAC治疗组IL-6含量在24 h内较SAP组显著降低(P<0.05);与SAP组相比,NAC组的TXB26-Keto-PGF1α含量在6、12和24 h点显著降低(P<0.05),但6-Keto-PGF1α含量无明显变化(P>0.05),T/P值在不同时间点也明显降低(P<0.05);SAP组、NAC治疗组与正常对照组相比,AMS含量显著性增高(P<0.05)。与SAP组相比,NAC治疗组从6 h时间点AMS含量开始显著降低(P<0.05),NAC治疗组进一步抑制了AMS的升高趋势。结论:NAC可通过改善SAP模型大鼠胰腺的微循环减轻胰腺炎的严重程度,在临床上治疗坏死性胰腺炎方面具有应用价值。

Objective： To investigate the value of N- acetylcysteine（NAC） promoting pancreatic microcirculation of rats with severe acute pancreatitis（SAP）. Methods： 54 rats were randomly divided into three groups ： controlled group（n=18）, SAP group（n=18）and NAC group（n=18）. The rats were supplied by Hebei medical university. 3.5% sodium taurocholate with 0.1mg/100 g dose was injected into pancreatic duct with minimpump to build the SAP rat model.SAP and NAC group was set time point in 6, 12, 24 hours respectively. 100 mg/kg dose of NAC was used in abdominal cavity. Pancreatic microcirculation was evaluated by measuring serum amylase 、IL- 6、TXB2、6- Keto- PGF1α and T/P. The sample of pancreatic head tissue was dyed with HE methods. The rat speciems were recorded by histopathological score. The infomation was processed by spss16.0 software. Results： Control group showed that the normal pancreatic tissue was no edema and effusion; SAP group showed the morphology of pancreatic tissue appear edema, inflammation effusion, harden tissue and hemorrhage necrosis, NAC group showed that pancreatic tissue was slightly swelling and distension. Pathological evaluation showed that the tissue injury, bleeding and necrosis in NAC group was dramatically alleviated than that in SAP group from 6h to 24 h. Pathological scores in NAC group obviously decreased at6 hours than those in SAP group（P0.05） and more obviously decreased at 12 h and 24 h.Pathological scores showed that there was significantly different between two groups（P0.05）.Contrast to SAP group, the serum amylase value in NAC group was obviously reduced in the different time point（P0.05）. Contrast to SAP group, serum IL- 6 level in NAC group was significantly reduced in the different time point（P0.05）. Contrast to SAP group, TXB2 value in NAC group significantly lowered in different time point（P0.05）, but 6- Keto- PGF1αlevels no significant change（P0.05）. T/P value decreased statistically（P0.05）. Conclusion： NAC can alleviate the severity of SAP through improving pancreatic microcirculation. It might be valuable and helpful for the clinical therapy of SAP.