摘要目的 探讨高脂血症对急性坏死性胰腺炎(ANP)大鼠胰腺组织病理损伤程度、NF-κB活化及胰腺腺泡细胞凋亡的影响.方法 50只雄性SD大鼠随机分成对照组、高脂血症组(HL组)、ANP组及HL+ANP组.对照组予均衡饲料喂养2周,仅开、关腹;HL组脂肪乳灌胃2周后开、关腹;ANP组予均衡饲料喂养2周后采用胰胆管注射牛磺胆酸钠制备ANP模型;HL+ANP组在脂肪乳灌胃2周后制备ANP模型.免疫组化法检测胰腺组织NF-κBp5及Fas、FasL蛋白表达,TUNEL法检测胰腺腺泡细胞凋亡.结果 HL组和HL+ANP组大鼠的血脂明显升高.HL组胰腺见部分细胞有脂质空泡形成,中等量炎症细胞浸润;NF-κB活化轻度增强;凋亡蛋白Fas、FasL表达也有所增强;凋亡指数从(0.62±0.28)%增加到(3.35±1.12)%.ANP组胰腺大片坏死,大量炎症细胞浸润;大量腺胞细胞核有NF-κBp65表达;Fas与FasL表达亦明显增强;凋亡指数为(2.20±1.78)%.HL+ANP组的胰腺坏死较ANP组更严重(3.4±0.7比2.4±1.1,P<0.05),NF-κB p65的表达阳性率及强度较ANP组更高;Fas与FasL的表达较ANP组有所减弱;凋亡指数为(0.93±0.87)%,较ANP组明显降低(P<0.05).结论 高血脂能增强ANP大鼠胰腺NF-κB的活化,抑制腺泡细胞的凋亡,减少Fas与FasL的表达,加重胰腺组织坏死,故必须控制高血脂以减轻胰腺炎的损伤程度.

abstractsObjective To investigate the effect of hyperlipidemia (HL) on the pancreatic injuries during acute necrotizing pancreatitis (ANP) as well as the activation of nuclear factor kappa B ( NF-κB) and pancreatic acinar cell apoptosis. Methods Fifty SD male rats were randomly divided into control group, hyperlipidemia ( HL) group, ANP group and HL + ANP group. Rats in control group were fed with balanced diet for 2 weeks, and underwent opening and closing of the abdomen. Rats in HL group received fat emulsion lavage, and then underwent opening and closing of the abdomen. Rats in ANP group were fed with balanced diet for 2 weeks, and were induced by retrograde injection of sodium taurocholate into the bili-pancreatic duct to establish the ANP model. Rats in HL + ANP group received fat emulsion lavage for 2 weeks, and were induced by retrograde injection of sodium taurocholate into the bili-pancreatic duct to establish the ANP model. NF-κB p65 and Fas, FasL protein expression were determined by immunohistochemical method and the apoptosis in pancreatic acinar cell were detected by TUNEL. Results Two weeks after fat emulsion lavage, rats in HL and HL + ANP group had significantly higher serum level of lipid. Lipid vacuoles were present in some pancreatic cells in the rats of HL group, and middle number of inflammatory cells infiltration was found, the activation of NF-κB was slightly enhanced; and the expression of Fas, FasL was also enhanced. Apoptosis index increased from (0.62 ±0.28)% to (3.3S ±1.12)%. Massive pancreatic tissue necrosis, large amount of inflammatory cells infiltration was found in ANP group. NF-κB p65 was present in large number of pancreatic nucleus. The expression of Fas and FasL was also increased; the apoptosis index was (2.20±1.78)%. The degree of pancreatic necrosis was greater in HL + ANP group than that in ANP group (3.4 ± 0.7 vs. 2.4 ± 1.1, P <0.05). The positive rate and density of NF-κB expression was higher than that in ANP group; and the expression of Fas and FasL was decreased more than that in ANP group; the apoptosis index was (0.93 ± 0.87)% , which was significantly lower than that in ANP group (P <0.05). Conclusions High level of lipid can increase the activation of NF-κB and inhibit the acinar cell apoptosis, and decrease the expression of Fas and FasL, increase the pancreatic tissue necrosis, therefore in order to attenuate the injury of pancreas, it is essential to control blood lipid.