血红素加氧酶-1对重症急性胰腺炎小鼠模型保护作用的实验研究

目的:探讨血晶素(hemin)诱导血红素加氧酶-1(hemeoxygenase-1,HO-1)过表达对重症急性胰腺炎(severe acute pancreatitis,SAP)大鼠的胰腺和肝脏功能的保护作用及其可能的机制。方法:将70只雄性SD大鼠随机分为4组,正常组10只;SAP模型组(经胰管逆行注射3%牛磺胆酸钠)20只;HO-1促进剂组(造模后30min腹腔注射血晶素75μg/kg)20只;HO-1抑制剂组(造模后30min腹腔注射锌原卟啉,Zn-protoporphyrin,Zn-PP,20μmol/kg)20只。造模后24h,每组各处死10只大鼠,另10只观察自然存活时间。采用ELISA法检测血清IL-10、HO-1、TNF-α含量;用多功能生化分析仪检测ALT、AST、TBIL、BUN、CREA含量;用免疫组化法检测胰、肝组织NF-κBp65蛋白表达的情况;用HE染色法观察胰、肝组织病理学改变。结果:与SAP模型组相比,HO-1促进剂组大鼠的血HO-1、IL-10含量均显著增高(P0.05),血TNF-α含量显著下降(P0.05),肝肾功能指标显著改善(P0.05),胰腺和肝脏病理改变有所减轻。而HO-1抑制剂组与HO-1促进剂组的指标变化相反。结论:HO-1过表达可改善SAP时的胰腺、肝脏病变及肝肾功能,其作用机制可能与促进IL-10表达、抑制NF-κB及TNF-α的表达有关。

Protective effects of heme oxygenase-1 on severe acute pancreatitis model:in vivo study

Objective Objective：To investigate the protective effects of hemo oxygenase-1 （HO-1） on the pancrease and liver in severe acute pancreatitis （SAP） rat model, and explore its possible mechanism. Methods A total of 70 male SD rats were randomly divided into 4 groups： （1） control group （n=10）, （2） SAP group （n=20）, 3% Sodium Cholate was retrogradedly injected into the pancreatic duct to produce the SAP model, （3） HO-1 stimulation group （n=20）, 75 μg/kg heroin was injected intraperitoneally at 30 minutes after model establishment, and （4） HO-1 inhibition group （n=20）, 20 μmol/kg ZnPP was injected intraperitoneally at 30 minutes after model establishment. Ten rats in each group were sacrificed 24 hours after the SAP model establishment, and the other 10 were remained for survival observation. Serum concentration of IL-10, HO-1 and TNF-α were detected by ELISA assay, serum ALT, AST, TBIL,BUN, and Creatinine were determined via biochemistry analysis. The NF-κB p65 protein expression in pancrease and liver tissues were detected by immunohistochemistry staining. Meanwhile, HE staining was performed to observe the histopathological changes in different groups. Results Compared with those in SAP model group, the serum HO-1 and IL-10 concentrations were significantly elevated in HO-1 stimulation group （P〈0.05）, while the serum TNF-α was significantly decreased （P〈0.05）. The hepato-renal parameters were amefiorated （P〈0.05） in HO-1 stimulation group. The severity of pathological changes of the pancrease and liver in HO-1 stimulation group were also palliated. Conclusions The results of this in vivo study demonstrated that HO-1 over-expression might compensate the damages of SAP on the pancrease and liver, as well as the hepato-renal function. Up-regulated IL-10 expression, down-regulated NF-κB and TNF-αmight be served as its potential mechanism.