RANTES在急性胰腺炎血-脑脊液屏障通透性变化中的作用

目的 观察急性胰腺炎(AP)大鼠脑组织正常T细胞表达与分泌的活化调节因子(regulated on activation,normal T-cell expressed and secreted,RANTES)和occludin在大脑中的表达,探讨RANTES表达与血-脑脊液屏障通透性变化之间的关系.方法 将49只SD大鼠按数字表法随机分为假手术(SO)组,急性水肿性胰腺炎(AEP)3、6 h组和急性坏死性胰腺炎(ANP)3、6、12、24 h组.以0.5%和5%牛磺胆酸钠逆行胰胆管注射制备AEP和ANP模型.采用RT-PCR、Western blotting和免疫组化法检测脑组织RANTES和occludin的mRNA及蛋白的表达.结果 SO组,AEP 3、6组,ANP 3、6、12、24 h组RANTES mRNA表达量分别为0、0、0、0.36±0.05、0.47 4-0.04、0.65 4-0.05、0.83±0.07,蛋白表达量为0、0、0、0.42±0.03、0.57±0.04、0.78±0.08、1.05±0.08,ANP组较SO组和AEP组显著增加(P<0.01);occludin mRNA表达量为1.21±0.07、1.17±0.07、1.15±0.08、0.84±0.07、0.77±0.05、0.64±0.09、0.56±0.09,蛋白表达量为1.18±0.08、1.16±0.10、1.11±0.10、0.90±0.03、0.65±0.05、0.57±0.05、0.48±0.05,ANP组较s0组和AEP组显著下降(P<0.01).RANTES表达与胰腺组织病理损伤呈正相关(r=0.936,P<0.001);occludin表达与胰腺组织病理损伤呈负相关(r=-0.900,P<0.001);RANTES和occludin呈负相关(r=-0.943,P<0.001).结论 ANP时大鼠脑组织RNANTES 表达呈进行性增高,occludin表达呈进行性下降,RANTES通过下调occludin蛋白表达而改变血-脑脊液屏障通透性.

Role of RANTES in the change of blood-brain barrier permeability in rats with acute pancreatitis

Objectiye To investigate the expression of regulated on activation, normal T-cell expressed and secreted (RANTES) and occluding in brain, and investigate the role of expression of RANTES in the change of blood-brain barrier permeability of rats with acute pancreatitis. Methods 49 Sprague-Dawley rats were randomly divided into 7 groups according to random number table, including sham-operated group (SO) , acute edematous pancreatitis (AEP) 3, 6 h group and acute necrotizing pancreatitis (ANP) 3, 6, 12 and 24 h group. AEP and ANP were induced by retrograde injection of 0. 5% and 5% sodium taurocholate, respectively. RT-PCR, Western blot, and immunohistochemistry methods were performed to assess the expression of RANTES and occludin mRNA and protein in brain tissue. Results The RANTES mRNA expressions in SO, AEP 3, 6 h, ANP 3, 6, 12, 24 h group were 0, 0, 0, 0.36±0.05, 0.47±0.04, 0.65±0.05, 0.83±0.07, respectively; The RANTES protein expressions were 0, 0, 0, 0.42±0. 03, 0. 57±0.04,0.78±0.08, 1.05±0.08, respectively; the values in ANP group were significantly lower than those in SO group and AEP group (P<0.01). The occludin mRNA expressions were 1.21±0.07,1.17±0.07, 1.15±0.08,0.84±0.07,0.77±0.05,0.64±0.09,0.56±0.09, respectively, the occludin protein expressions were 1.18 ±0.08, 1. 16 ±0. 10, 1. 11 ±0. 10, 0. 90 ±0. 03, 0. 65 ±0."05, 0.57 ±0.05, 0.48 ±0.05, respectively, the values in ANP group were significantly lower than those in SO group and AEP group (P< 0.01). The expression of RANTES was positively related to the pancreatic pathologic score (r = 0. 936,P< 0. 001) ; the expression of occluding was negatively related to the pancreatic pathologic score (r = - 0. 943, P < 0.001). The expression of RANTES was negatively related to the expression of occluding (r = -0. 943, P <0. 001). Conclusions The expression of RANTES was progressively increased in the brain tissue in rats with ANP, while the expression of occluding was progressively decreased; RANTES may play an important role in the change of blood-brain barrier permeability via down-regulating the expression of occluding.