恶性阻塞性黄疸患者围手术期外周血淋巴细胞蛋白激酶C活性

Protein kinase C signal pathway during operation in patients with malignant bile duct obstruction

目的研究蛋白激酶C信号通道在恶性阻塞性黄疸患者围手术期中的作用,为恶性阻塞性黄疸的临床治疗提供新途径。方法抽取正常组、恶性阻塞性黄疸患者术前、术后1wk、2wk清晨空腹静脉血8ml。采用同位素γ-^(32)P-ATP催化活性测定法检测31例恶性阻塞性黄疸患者手术前后外周静脉血中淋巴细胞PKC活性,ELISA法测血清TNFa浓度,并与正常组比较。结果①与正常组相比,恶性阻塞性黄疸患者术前、术后1wk、2wk淋巴细胞PKC总活性显著升高,胞膜PKC活性明显增强,他占PKC总活性的百分比也明显提高,且恶性阻塞性黄疸组术前术后淋巴细胞中均超过10％的胞浆PKC转位至胞膜(P<0.01);恶性阻塞性黄疸组术后1wk、2wk,PKC活性仍维持较高的水平,与术前相比无显著性差异(P>0.05)。②与正常组相比,恶性阻塞性黄疸患者术前、术后1wk、2wk血清TNFa浓度较正常组明显升高(P<0.05),术后1wk、2wk、血清TNFa浓度仍维持较高的水平,与术前相比无显著性差异。③随黄疸程度的加深,恶性阻塞性黄疸患者PKC活性及血清TNFa浓度均增加。结论 PKC信号通道的持续激活与TNFa的持续增高,可能是恶性阻塞性黄疸患者围手术期并发症增加的原因之一。

AIM To study the roles of protein Kinase C signal pathway during the operation and find a new way for treating patients with malignant bile duct obstruction. METHODS Peripheral blood of normal subjects, and patients with malignant bile duct obstruction before and 1 and 2 weeks after operation was taken by venipuncture using heparin (25u/ml) as anticoagulant. PKC activities of peripheral blood lymphocytes were determined by radioactive isotope γ-^(32) P-ATP-catalyzing assay and plasma concentrations of TNFa by ELISA from 31 patients, and was compared with those in normal subjects. RESULTS ①The total PKC activities of PBL in patients with malignant obstructive jaundice before and 1 and 2 weeks after operation were significantly (p<0.01) higher than in normal subjects. Moreover, the membrane PKC activities and their percentages of the total PKC activities were higher in malignant obstructive jaundice than in normal subjects (p<0.01). The PKC activities of malignant obstructive jaundice before and 1 and 2 weeks after operation were still higher and there is no difference as compared with before operation (p>0.05). ②The TNFa in serum in patients with malignant obstructive jaundice before and 1 and 2 weeks after operation were significantly (p<0.01) higher than those in normal subjects. The TNFa of malignant obstructive jaundice before and 1 and 2 weeks after operation were still high and there is no difference as compared with before operation (p>0.05). ③The total PKC activities and the densities of TNFa in PBL were positively correlated with the degree of jaundice (T-BIL) (r=0.58, p<0.01) in serum. CONCLUSIONS The increase of PKC activities and plasma concentrations of TNFa may raise the rate of complications during the operation in patients with malignant bile duct obstruction.